Search results for: drug policy

Authors: Meenu Mehta, Munish Garg

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The use of oral anticancer drugs from AYUSH system of medicine is widely increased among the society due to their low cost, enhanced efficacy, increased patient preference, lack of inconveniences related to infusion and they provide an opportunity to develop chronic treatment regimens. However, oral delivery of these drugs usually laid down by the limited bioavailability of the drug, which is associated with a wide variation. As most of the cytotoxic agents have a narrow therapeutic window and are dosed at or near the maximum tolerated dose, a wide variability in the bioavailability can negatively affect treatment result. It is estimated that 40% of active substances are poorly soluble in water. The improvement of bio-availability of drugs with such properties presents one of the greatest challenges in drug formulations. There are several techniques reported in literature. Among all these Self Emulsifying Drug Delivery System (SEDDS) has gained more attention due to enhanced oral bio-availability enabling a reduction in dose. Thus, SEDDS anticancer drugs will have the increased bioavailability and efficacy. These dosage form will provide societal benefit in a cost-effective manner as compared to other oral dosage forms. Present study reflects on the formulation strategies as SEDDS for oral anticancer agents of AYUSH system for enhanced bioavailability with proven efficacy by cancer cell lines.

Keywords: anticancer agents, AYUSH system, bioavailability, SEDDS

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Authors: Olakunle Felix Adekunle

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In the recent years several non-tariff provisions have been regarded as means holding back transboundary environmental damages. Affected countries have then increasingly come up with trade policies to compensate for or to In recent years, several non‐tariff trade provisions have been regarded as means of holding back transboundary environmental damages. Affected countries have then increasingly come up with trade policies to compensate for or to enforce the adoption of environmental policies elsewhere. These non‐tariff trade constraints are claimed to threaten the freedom of trading across nations, as well as the harmonization sought towards the distribution of income and policy measures. Therefore the ‘greening’ of world trade issues essentially ranges over whether there ought or ought not to be a trade‐off between trade and environmental policies. The impacts of free trade and environmental policies on major economic variables (such as trade flows, balances of trade, resource allocation, output, consumption and welfare) are thus studied here, and so is the EKC hypothesis, when such variables are played against the resulting emission levels. The policy response is seen as a political game, played here by two representative parties named North and South. Whether their policy choices, simulated by four scenarios, are right or wrong depends on their policy goals, split into economic and environmental ones.

Keywords: environmental, policies, strategies, constraint

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Authors: S. Mohamed, D. Gonzalez, C. Sayada, P. Halfon

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Drug resistance mutations are routinely detected using standard Sanger sequencing, which does not detect minor variants with a frequency below 20%. The impact of detecting minor variants generated by ultra-deep sequencing (UDS) on HIV drug-resistance (DR) interpretations has not yet been studied. Fifty HIV-1 patients who experienced virological failure were included in this retrospective study. The HIV-1 UDS protocol allowed the detection and quantification of HIV-1 protease and reverse transcriptase variants related to genotypes A, B, C, E, F, and G. DeepChek®-HIV simplified DR interpretation software was used to compare Sanger sequencing and UDS. The total time required for the UDS protocol was found to be approximately three times longer than Sanger sequencing with equivalent reagent costs. UDS detected all of the mutations found by population sequencing and identified additional resistance variants in all patients. An analysis of DR revealed a total of 643 and 224 clinically relevant mutations by UDS and Sanger sequencing, respectively. Three resistance mutations with > 20% prevalence were detected solely by UDS: A98S (23%), E138A (21%) and V179I (25%). A significant difference in the DR interpretations for 19 antiretroviral drugs was observed between the UDS and Sanger sequencing methods. Y181C and T215Y were the most frequent mutations associated with interpretation differences. A combination of UDS and DeepChek® software for the interpretation of DR results would help clinicians provide suitable treatments. A cut-off of 1% allowed a better characterisation of the viral population by identifying additional resistance mutations and improving the DR interpretation.

Keywords: HIV-1, ultra-deep sequencing, Sanger sequencing, drug resistance

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Authors: Pedro G. Rodrigues, Maria J. Bárrios, Sara A. Ambrósio

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The digitalisation of health is a profoundly transformative economic, political, and social process. As is often the case, such processes need to be carefully managed if misunderstandings, policy misalignments, or outright conflicts between the government and a wide gamut of stakeholders with competing interests are to be avoided. Thus, ensuring open lines of communication where all parties know what each other’s concerns are is key to good governance, as well as efficient and effective policymaking. This project aims to make a small but still significant contribution in this regard in that we seek to determine the extent to which health managers’ perceptions of what is a priority for digital health in Portugal are aligned with official policy perspectives. By applying state-of-the-art artificial intelligence technology first to the indexed literature on digital health and then to a set of official policy documents on the same topic, followed by a survey directed at health managers working in public and private hospitals in Portugal, we obtain two priority rankings that, when compared, will allow us to produce a synthesis and toolkit on digital health policy in Portugal, with a view to identifying areas of policy convergence and divergence. This project is also particularly peculiar in the sense that sophisticated digital methods related to text analytics are employed to study good governance aspects of digitalisation applied to health care.

Keywords: digital health, health informatics, text analytics, governance, natural language understanding

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Authors: Prakriti Diwan, S. Saraf

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The present study involves preparation and evaluation of microparticles of diclofenac sodium. The microparticles were prepared by the emulsion solvent evaporation techniques using ethylcellulose polymer. Four different batches of microspheres were prepared by varying the concentration of polymer from 50% to 80% w/w. The microspheres were characterized for drug content, percentage yield and encapsulation efficiency, particle size analysis and surface morphology. Microsphere prepared with high drug content produces higher percentage yield and encapsulation efficiency values. It was observed the increase in concentration of the polymer, increases the mean particle size of the microspheres. The effect of polymer concentration on the in vitro release of diclofenac from the microspheres was also studied. The production microparticles yield showed 98.74%, mean particle size 956.32µm and loading efficiency 97.15%. The results were found that microparticles prepared had slower release than microparticles (p>0.05). Therefore, it may be concluded that drug loaded microparticles are suitable delivery systems for diclofenac sodium.

Keywords: diclofenac sodium, emulsion solvent evaporation, ethylcellulose, microparticles

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Authors: Hamza Iftikhar

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The research study focuses on the transgender community's gender recognition challenges. It is one of the issues for the transgender community, interacting directly with the difficulties of gender identity and the lives of these people who are facing gender disapproval from society. This study investigates the major flaws of the transgender act. The study's goal is to look into the strange implications of self-perceived identity as a policy tool for transgender recognition. This policy tool jeopardises the rights of Pakistan's indigenous gender-variant people as well as the country's legal and social framework. Qualitative research using semi structured interviews will be carried out. This study proposes developing a scheme for mainstreaming gender-variant people on the basis of the Pakistani Constitution, Supreme Court guidelines, and internationally recognised principles of law. This would necessitate a thorough review of current law using a new approach and reference point.

Keywords: transgender act, self perceived identity, gender variant, policy tool

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Authors: Majid Farsadrooh, Mehran Feizi-Dehnayebi

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Serum albumin is the most abundant protein that is present in the circulatory system of a wide variety of organisms. Although it is a significant macromolecule, it can contribute to osmotic blood pressure and also, plays a superior role in drug disposition and efficiency. Molecular docking simulation can improve in silico drug design and discovery procedures to propound a lead compound and develop it from the discovery step to the clinic. In this study, the molecular docking simulation was applied to select a lead molecule through an investigation of the interaction of the two anticancer drugs (Alitretinoin and Abemaciclib) with Human Serum Albumin (HSA). Then, a series of new compounds (a-e) were suggested using lead molecule modification. Density functional theory (DFT) including MEP map and HOMO-LUMO analysis were used for the newly proposed compounds to predict the reactivity zones on the molecules, stability, and chemical reactivity. DFT calculation illustrated that these new compounds were stable. The estimated binding free energy (ΔG) values for a-e compounds were obtained as -5.78, -5.81, -5.95, -5,98, and -6.11 kcal/mol, respectively. Finally, the pharmaceutical properties and toxicity of these new compounds were estimated through OSIRIS DataWarrior software. The results indicated no risk of tumorigenic, irritant, or reproductive effects and mutagenicity for compounds d and e. As a result, compounds d and e, could be selected for further study as potential therapeutic candidates. Moreover, employing molecular docking simulation with the prediction of pharmaceutical properties helps to discover new potential drug compounds.

Keywords: drug design, anticancer, computational studies, DFT analysis

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Authors: Afolabi O.J, Simon-Oke I.A., Oniya M.O., Okaka C.E.

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River blindness is a skin, and an eye disease caused by Onchocerca volvulus and vectored by a female hematophagous blackfly. The study aims to evaluate the distribution of the clinical signs of river blindness and the efficacy of ivermectin in the treatment of river blindness in Idogun. Observational studies in epidemiology that involve the use of a structured questionnaire to obtain useful epidemiological information from the respondents, physical assessment via palpation from head to ankle was used to assess clinical signs from the respondents and skin snip test was used to evaluate the prevalence of the disease. The efficacy of the drug was evaluated and expressed in percentages. One hundred and ninety-two (192) out of the 384 respondents examined, showed various signs of river blindness. However, it was only 108 (28.1%) respondents with the clinical signs that demonstrated Onchocerca volvulus microfilariae in their skin snips. The clinical signs observed among the respondents include skin depigmentation such as dermatitis, leopard skin, papules, pruritus and self-inflicted injury, while ocular symptoms include cataract, ocular lesion and partial blindness. Among these clinical signs, papules, and pruritus were the most dominant in the community. The prevalence of the clinical signs was observed to vary significantly among the age groups and gender (P<0.05). The efficacy of the drug after 6 and 12 months of treatments shows that the drug is more effective at age groups 10-50 years than the age groups 51-90 years. Ivermectin is observed to be efficacious in the treatment of the disease. However, to achieve eradication of the disease, the drug may be administered at 0.15mg/kg twice a year.

Keywords: riverblindness, clinical signs, ivermectin, Idogun

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Authors: Minwuyelet Maru, Solomon Habtemariam, Endalamaw Gadissa, Abraham Aseffa

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Background: Tuberculosis is a major public health problem in Ethiopia. The burden of TB is aggravated by emergence and expansion of drug resistant tuberculosis and different lineages of Mycobacterium tuberculosis (M. tuberculosis) have been reported in many parts of the country. Describing strains of Mycobacterial isolates and drug susceptibility pattern is necessary. Method: Sputum samples were collected from smear positive pulmonary TB patients age >= 7 years between October 1, 2012 to September 30, 2013 and Mycobacterial strains isolated on Loweensten Jensen (LJ) media. Each strain was characterized by deletion typing and Spoligotyping. Drug sensitivity testing was determined with the indirect proportion method using Middle brook 7H10 media and association to determine possible risk factors to drug resistance was done. Result: A total of 144 smear positive pulmonary tuberculosis patients were enrolled. The age of participants ranged from 7 to 78 with mean age of 29.22 (±10.77) years. In this study 82.2% (n=97) of the isolates were sensitive to the four first line anti-tuberculosis drugs and resistance to any of the four drugs tested was 17.8% (n=21). A high frequency of any resistance was observed in isoniazid, 13.6%, (n=16) followed by streptomycin, 11.8% (n=14). No significant association of isoniazid resistance with HIV, sex and history of previous TB treatment was observed but there was significant association with age, high between 31-35 years of age (p=0.01). Majority, 89.9% (n=128) of participants were new cases and only 11.1% (n=16) had history of previous TB treatment. No MDR-TB from new cases and 2 MDRTB (13.3%) was isolated from re-treatment cases which was significantly associated with previous TB treatment (p<0.01). Thirty two different types of spoligotype patterns were identified and 74.1% were grouped in to 13 clusters. The dominant strains were SIT 25, 18.1% (n=21), SIT 53, 17.2% (n=20) and SIT 149, 8.6% (n=10). Lineage 4 is the predominant lineage followed by lineage 3 and lineage 7 comprising 65.5% (n=76), 28.4% (n=33) and 6% (n=7) respectively. Majority of strains from lineage 3 and 4 were SIT 25 (63.6%) and SIT 53 (26.3%) whereas SIT 343 was the dominant strain from lineage 7 (71.4%). Conclusion: Wide spread of lineage 3 and lineage 4 of the modern lineage and high number of strain cluster indicates high ongoing transmission. The high proportion resistance to any of the first line anti-tuberculosis drugs may be a potential source in the emergence of MDR-TB. Wide spread of SIT 25 and SIT 53 having a tendency of ease transmission and presence of higher resistance of isoniazid in working and mobile age group, 31-35 years of age may increase risk of drug resistant strains transmission.

Keywords: tuberculosis, drug susceptibility, strain diversity, lineage, Ethiopia, spoligotyping

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Authors: Sheraz Gul

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The requirements for progressing a compound to clinical trials is well established and relies on the results from in-vitro and in-vivo animal tests to indicate that it is likely to be safe and efficacious when testing in humans. The typical data package required will include demonstrating compound safety, toxicity, bioavailability, pharmacodynamics (potential effects of the compound on body systems) and pharmacokinetics (how the compound is potentially absorbed, distributed, metabolised and eliminated after dosing in humans). If the desired criteria are met and the compound meets the clinical Candidate criteria and is deemed worthy of further development, a submission to regulatory bodies such as the US Food & Drug Administration for an exploratory Investigational New Drug Study can be made. The purpose of this study is to collect data to establish that the compound will not expose humans to unreasonable risks when used in limited, early-stage clinical studies in patients or normal volunteer subjects (Phase I). These studies are also designed to determine the metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on their effectiveness. In order to reach the above goals, we have developed a pre-clinical high throughput Absorption, Distribution, Metabolism and Excretion–Toxicity (ADME–Toxicity) panel of assays to identify compounds that are likely to meet the Lead and Candidate compound acceptance criteria. This panel includes solubility studies in a range of biological fluids, cell viability studies in cancer and primary cell-lines, mitochondrial toxicity, off-target effects (across the kinase, protease, histone deacetylase, phosphodiesterase and GPCR protein families), CYP450 inhibition (5 different CYP450 enzymes), CYP450 induction, cardio-toxicity (hERG) and gene-toxicity. This panel of assays has been applied to multiple compound series developed in a number of projects delivering Lead and clinical Candidates and examples from these will be presented.

Keywords: absorption, distribution, metabolism and excretion–toxicity , drug discovery, food and drug administration , pharmacodynamics

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Authors: Ji-Chan Jang

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Tuberculosis is still major health problem because there is an increase of multidrug-resistant and extensively drug-resistant forms of the disease. Therefore, the most urgent clinical need is to discover potent agents and develop novel drug combination capable of reducing the duration of MDR and XDR tuberculosis therapy. Three reference strains H37Rv, CDC1551, W-Beijing GC1237 and six clinical isolates of MDRTB were tested to daptomycin in the range of 0.013 to 256 mg/L. Daptomycin is resistant to all tested M. tuberculosis strains not only laboratory strains but also clinical MDR strains that were isolated at different source. Daptomycin will not be an antibiotic of choice for treating infection of Gram positive atypical slowly growing M. tuberculosis.

Keywords: tuberculosis, daptomycin, resistance, Mycobacterium tuberculosis

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Authors: Aleksandra Szunke

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Monetary policy is an important pillar of the economy, directly affecting on the condition of banking sector. Depending on the strategy may both support functioning of banking institutions, as well as limit their excessively risky activities. The literature studies indicate a large number of publications, which include characteristics of initiatives, implemented by central banks during the global financial crisis and the potential effects of the use of non-standard monetary policy instruments. However, the empirical evidence about their effects and real consequences for the financial markets are still not final. Even before the escalation of instability, Bernanke, Reinhart, and Sack (2004) analyzed the effectiveness of various unconventional monetary tools in lowering long-term interest rates in the United States and Japan. The obtained results largely confirmed the effectiveness of the zero-interest-rate policy and Quantitative Easing (QE) in achieving the goal of reducing long-term interest rates. Japan, considered as the precursor of QE policy, also conducted research about the consequences of non-standard instruments, implemented to restore financial stability of the country. Although the literature about the effectiveness of Quantitative Easing in Japan is extensive, it does not uniquely specify whether it brought permanent effects. The main aim of the study is to identify the implications of non-standard monetary policy, implemented by selected central banks (the Federal Reserve System, Bank of England and European Central Bank), paying particular attention to the consequences into three areas: the size of money supply, financial markets, and the real economy.

Keywords: consequences of modern monetary policy, quantitative easing policy, banking sector instability, global financial crisis

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Authors: Deepti Kohli, Meeta Keswani Mehra

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The paper develops a theoretical model of electoral competition with purely opportunistic candidates and a uni-dimensional policy using the probability voting approach while focusing on the aspect of lobby formation to analyze the inherent complex interactions between centripetal and centrifugal forces and their effects on equilibrium policy platforms. There exist three types of agents, namely, Left-wing, Moderate and Right-wing who comprise of the total voting population. Also, it is assumed that the Left and Right agents are free to initiate a lobby of their choice. If initiated, these lobbies generate donations which in turn can be contributed to one (or both) electoral candidates in order to influence them to implement the lobby’s preferred policy. Four different lobby formation scenarios have been considered: no lobby formation, only Left, only Right and both Left and Right. The equilibrium policy platforms, amount of individual donations by agents to their respective lobbies and the contributions offered to the electoral candidates have been solved for under each of the above four cases. Since it is assumed that the agents cannot coordinate each other’s actions during the lobby formation stage, there exists a probability with which a lobby would be formed, which is also solved for in the model. The results indicate that the policy platforms of the two electoral candidates converge completely under the cases of no lobby and both (extreme) formations but diverge under the cases of only one (Left or Right) lobby formation. This is because in the case of no lobby being formed, only the centripetal forces (emerging from the election-winning aspect) are present while in the case of both extreme (Left-wing and Right-wing) lobbies being formed, centrifugal forces (emerging from the lobby formation aspect) also arise but cancel each other out, again resulting in a pure policy convergence phenomenon. In contrast, in case of only one lobby being formed, both centripetal and centrifugal forces interact strategically, leading the two electoral candidates to choose completely different policy platforms in equilibrium. Additionally, it is found that in equilibrium, while the donation by a specific agent type increases with the formation of both lobbies in comparison to when only one lobby is formed, the probability of implementation of the policy being advocated by that lobby group falls.

Keywords: electoral competition, equilibrium policy platforms, lobby formation, opportunistic candidates

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Authors: Samiah Rehman, Kashmira J. Gohil

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Objective: Dracaena trifascaita extract (DTE) possesses strong antioxidant and anti-inflammatory properties that play a vital role in the treatment of mental disorders like depression. The present study was designed to evaluate the antidepressant effects of hydroalcoholic extracts of DT on behavioral models of depression. Methodology: Animals were randomly divided into 6 groups of 5 each: Group 1 and 2 received distilled water and standard drug, imipramine: 25mg/kg, respectively. Groups 4, 5 and 6 received DTE treatment orally at doses of 200 ,400 and 600mg/ kg, respectively, for 14 days. Time of immobility was noted by force swimming test (FST)and tail suspension test (TST) on the 1st,7th and 14th days. Results: The time of immobility was reduced in the treatment group as compared to the control and standard. DTE600 mg/kg showed the highest and most significant antidepressant effects as compared to the standard drug imipramine. (25mg/kg). Conclusion: DTE has good potential as an alternative therapy for depression.

Keywords: Dracaena trifasciata, antidepressants, force swimming test, tail suspension test, herbal drug of depression

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Authors: Susan Amirsalari, Azime Khosrinejad, Elham Rahimian

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Objective: Epilepsy is a common brain disorder characterized by a persistent tendency to develop in neurological, cognitive, and psychological contents. Magnetic Resonance Imaging (MRI) is a neuroimaging test facilitating the detection of structural epileptogenic lesions. This study aimed to compare the MRI findings between patients with intractable and drug-responsive epilepsy. Material & methods: This case-control study was conducted from 2007 to 2019. The research population encompassed all 1-16- year-old patients with intractable epilepsy referred to the Shafa Neuroscience Center (n=72) (a case group) and drug-responsive patients referred to the pediatric neurology clinic of Baqiyatallah Hospital (a control group). Results: There were 72 (23.5%) patients in the intractable epilepsy group and 200 (76.5%) patients in the drug-responsive group. The participants' mean age was 6.70 ±4.13 years, and there were 126 males and 106 females in this study Normal brain MRI was noticed in 21 (29.16%) patients in the case group and 184 (92.46%) patients in the control group. Neuronal migration disorder (NMD)was also exhibited in 7 (9.72%) patients in the case group and no patient in the control group. There were hippocampal abnormalities and focal lesions (mass, dysplasia, etc.) in 10 (13.88%) patients in the case group and only 1 (0.05%) patient in the control group. Gliosis and porencephalic cysts were presented in 3 (4.16%) patients in the case group and no patient in the control group. Cerebral and cerebellar atrophy was revealed in 8 (11.11%) patients in the case group and 4 (2.01%) patients in the control group. Corpus callosum agenesis, hydrocephalus, brain malacia, and developmental cyst were more frequent in the case group; however, the difference between the groups was not significant. Conclusion: The MRI findings such as hippocampal abnormalities, focal lesions (mass, dysplasia), NMD, porencephalic cysts, gliosis, and atrophy are significantly more frequent in children with intractable epilepsy than in those with drug-responsive epilepsy.

Keywords: magnetic resonance imaging, intractable epilepsy, drug responsive epilepsy, neuronal migrational disorder

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Authors: Sharif Abdelghany

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Polymeric nanoparticles have been widely investigated as a controlled release drug delivery platform for the treatment of tuberculosis (TB). These nanoparticles were also readily internalised into macrophages, leading to high intracellular drug concentration. In this study two anti-TB drugs, amikacin and moxifloxacin were encapsulated into PLGA nanoparticles. The novelty of this work appears in: (1) the efficient encapsulation of two hydrophilic second-line anti-TB drugs, and (2) intramacrophage delivery of this synergistic combination potentially for rapid treatment of multi-drug resistant TB (MDR-TB). Two water-oil-water (w/o/w) emulsion strategies were employed in this study: (1) alginate coated PLGA nanoparticles, and (2) alginate entrapped PLGA nanoparticles. The average particle size and polydispersity index (PDI) of the alginate coated PLGA nanoparticles were found to be unfavourably high with values of 640 ± 32 nm and 0.63 ± 0.09, respectively. In contrast, the alginate entrapped PLGA nanoparticles were within the desirable particle size range of 282 - 315 nm and the PDI was 0.08 - 0.16, and therefore were chosen for subsequent studies. Alginate entrapped PLGA nanoparticles yielded a drug loading of over 10 µg/mg powder for amikacin, and more than 5 µg/mg for moxifloxacin and entrapment efficiencies range of approximately 25-31% for moxifloxacin and 51-59% for amikacin. To study macrophage uptake efficiency, the nanoparticles of alginate entrapped nanoparticle formulation were loaded with acridine orange as a marker, seeded to THP-1 derived macrophages and viewed under confocal microscopy. The particles were readily internalised into the macrophages and highly concentrated in the nucleus region. Furthermore, the anti-mycobacterial activity of the drug-loaded particles was evaluated using M. tuberculosis-infected macrophages, which revealed a significant reduction (4 log reduction) of viable bacterial count compared to the untreated group. In conclusion, the amikacin-moxifloxacin alginate entrapped PLGA nanoparticles are promising for further in vivo studies.

Keywords: moxifloxacin and amikacin, nanoparticles, multidrug resistant TB, PLGA

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Authors: Michael Kho Lim

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This paper examines the status of the film industry as an industry in the Philippines—where or how it is classified in the Philippine industrial classification system and how this positioning gives the film industry an identity (or not) and affects (film) policy development and impacts the larger national economy. It is important to look at how the national government recognises Philippine cinema officially, as this will have a direct and indirect impact on the industry in terms of its representation, conduct of business, international relations, and most especially its implications on policy development and implementation. Therefore, it is imperative that the ‘identity’ of Philippine cinema be clearly established and defined in the overall industrial landscape. Having a clear understanding of Philippine cinema’s industry status provides a better view of the bigger picture and helps us determine cinema’s position in the national agenda in terms of priority setting, future direction and how the state perceives and thereby values the film industry as an industry. This will then serve as a frame of reference that will anchor the succeeding discussion. Once the Philippine film industry status is identified, the paper will then clarify how cultural policy is defined, understood, and applied in the Philippines in relation to Philippine cinema by reviewing and analyzing existing policy documents and pending bills in the Philippine Congress and Senate. Lastly, the paper delves into the roles that (national) cultural institutions and industry organisations play as primary drivers or support mechanisms and how they become platforms (or not) for the upliftment of the independent film sector and towards the sustainability of the film industry. The paper concludes by arguing that the role of the government and how government officials perceive and treats culture is far more important than cultural policy itself, as these policies emanate from them.

Keywords: cultural and creative industries, cultural policy, film industry, Philippine cinema

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Authors: Mohsen Shati, Seyede Salehe Mortazavi, Seyed Kazem Malakouti, Hamidreza Khanke Fazlollah Ahmadi

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Taking unnecessary or excessive medication or using drugs with no indication (polypharmacy) by people of all ages, especially the elderly, is associated with increased adverse drug reactions (ADR), medical errors, hospitalization and escalating the costs. It may be facilitated or impeded by the healthcare system. In this study, we are going to describe the role of the health system in the practice of polypharmacy in Iranian elderly. In this Inductive qualitative content analysis using Graneheim and Lundman methods, purposeful sample selection until saturation has been made. Participants have been selected from doctors, pharmacists, policy-makers and the elderly. A total of 25 persons (9 men and 16 women) have participated in this study. Data analysis after incorporating codes with similar characteristics revealed 14 subcategories and six main categories of the referral system, physicians’ accessibility, health data management, drug market, laws enforcement, and social protection. Some of the conditions of the healthcare system have given rise to polypharmacy in the elderly. In the absence of a comprehensive specialty and subspecialty referral system, patients may go to any physician office so may well be confused about numerous doctors' prescriptions. Electronic records not being prepared for the patients, failure to comply with laws, lack of robust enforcement for the existing laws and close surveillance are among the contributing factors. Inadequate insurance and supportive services are also evident. Age-specific care providing has not yet been institutionalized, while, inadequate specialist workforce playing a major role. So, one may not ignore the health system as contributing factor in designing effective interventions to fix the problem.

Keywords: elderly, polypharmacy, health system, qualitative study

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Authors: Junie B. Billones, Maria Constancia O. Carrillo, Voltaire G. Organo, Stephani Joy Y. Macalino, Inno A. Emnacen, Jamie Bernadette A. Sy

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The drug discovery and development process is generally known to be a very lengthy and labor-intensive process. Therefore, in order to be able to deliver prompt and effective responses to cure certain diseases, there is an urgent need to reduce the time and resources needed to design, develop, and optimize potential drugs. Computer-aided drug design (CADD) is able to alleviate this issue by applying computational power in order to streamline the whole drug discovery process, starting from target identification to lead optimization. This drug design approach can be predominantly applied to diseases that cause major public health concerns, such as tuberculosis. Hitherto, there has been no concrete cure for this disease, especially with the continuing emergence of drug resistant strains. In this study, CADD is employed for tuberculosis by first identifying a key enzyme in the mycobacterium’s metabolic pathway that would make a good drug target. One such potential target is the lipoate protein ligase B enzyme (LipB), which is a key enzyme in the M. tuberculosis metabolic pathway involved in the biosynthesis of the lipoic acid cofactor. Its expression is considerably up-regulated in patients with multi-drug resistant tuberculosis (MDR-TB) and it has no known back-up mechanism that can take over its function when inhibited, making it an extremely attractive target. Using cutting-edge computational methods, compounds from AnalytiCon Discovery Natural Derivatives database were screened and docked against the LipB enzyme in order to rank them based on their binding affinities. Compounds which have better binding affinities than LipB’s known inhibitor, decanoic acid, were subjected to in silico toxicity evaluation using the ADMET and TOPKAT protocols. Out of the 31,692 compounds in the database, 112 of these showed better binding energies than decanoic acid. Furthermore, 12 out of the 112 compounds showed highly promising ADMET and TOPKAT properties. Future studies involving in vitro or in vivo bioassays may be done to further confirm the therapeutic efficacy of these 12 compounds, which eventually may then lead to a novel class of anti-tuberculosis drugs.

Keywords: pharmacophore, molecular docking, lipoate protein ligase B (LipB), ADMET, TOPKAT

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Authors: Chia-Chi Cheng

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After the implementation of “the internet plus,” several puzzles emerge as below: why does China impose more regulation and laws on economic development on the Internet? Why does China urge the importance of manufacturing industry? Why does China’s local government passively implement the policy imposed by the central government? What kind of factors can influence China’s local government’s economic preference? In the framework of neo-institutionalism, this research considers China’s local government as changing agents to analyze its preferences and behavior. In general, the interests urged by the local government will decide its preference and behaviors. They will change its counterpart to cooperate if the change will bring more benefits. Thus, they will change its preference and behavior while the external environment alters. While the local government has the same definition on political activity and economic interest, they will prefer to cooperate with the local enterprises in the way of laying symbiont, within the presumption that the institution remains. While the local government has the different positions on political activity and economic interest, they will re-define the existed regulation or create new regulation in the condition of institution vacuum. Sequentially, they will replace the targets, and the policy, which does not fit in the Central government’s policy, will emerge.

Keywords: China, institutional change, government enterprise relationship, e-commercial policy

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Authors: Raymond Ndhlovu, Jen Snowball

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It has long been known that the Cultural and Creative Industries (CCIs) have the potential to aid in physical, social and economic renewal and regeneration of towns and cities, hence their importance when dealing with regional development. The CCIs can act as a catalyst for activity and investment in an area because the ‘consumption’ of cultural activities will lead to the activities and use of other non-cultural activities, for example, hospitality development including restaurants and bars, as well as public transport. ‘Consumption’ of cultural activities also leads to employment creation, and diversification. However, CCIs tend to be clustered, especially around large cities. There is, moreover, a case for development of CCIs around smaller towns and cities, because they do not rely on high technology inputs, and long supply chains, and, their direct link to rural and isolated places makes them vital in regional development. However, there is currently little research on how to craft cultural policy for regions with smaller towns and cities. Using the Sarah Baartman District (SBDM) in South Africa as an example, this paper describes the process of developing cultural policy for a region that has potential, and existing, cultural clusters, but currently no one, coherent policy relating to CCI development. The SBDM was chosen as a case study because it has no large cities, but has some CCI clusters, and has identified them as potential drivers of local economic development. The process of developing cultural policy is discussed in stages: Identification of what resources are present; including human resources, soft and hard infrastructure; Identification of clusters; Analysis of CCI labour markets and ownership patterns; Opportunities and challenges from the point of view of CCIs and other key stakeholders; Alignment of regional policy aims with provincial and national policy objectives; and finally, design and implementation of a regional cultural policy.

Keywords: cultural and creative industries, economic impact, intrinsic value, regional development

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Authors: Fei Ye, Åsa Barrefelt, Manuchehr Abedi-Valugerdi, Khalid M. Abu-Salah, Salman A. Alrokayan, Mamoun Muhammed, Moustapha Hassan

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With appropriate encapsulation in functional nanoparticles drugs are more stable in physiological environment and the kinetics of the drug can be more carefully controlled and monitored. Furthermore, targeted drug delivery can be developed to improve chemotherapy in cancer treatment, not only by enhancing intracellular uptake by target cells but also by reducing the adverse effects in non-target organs. Inorganic imaging agents, delivered together with anti-cancer drugs, enhance the local imaging contrast and provide precise diagnosis as well as evaluation of therapy efficacy. We have developed biodegradable polymeric vesicles as a nanocarrier system for multimodal bio-imaging and anticancer drug delivery. The poly (lactic-co-glycolic acid) PLGA) vesicles were fabricated by encapsulating inorganic imaging agents of superparamagnetic iron oxide nanoparticles (SPION), manganese-doped zinc sulfide (MN:ZnS) quantum dots (QDs) and the anticancer drug busulfan into PLGA nanoparticles via an emulsion-evaporation method. T2-weighted magnetic resonance imaging (MRI) of PLGA-SPION-Mn:ZnS phantoms exhibited enhanced negative contrast with r2 relaxivity of approximately 523 s-1 mM-1 Fe. Murine macrophage (J774A) cellular uptake of PLGA vesicles started fluorescence imaging at 2 h and reached maximum intensity at 24 h incubation. The drug delivery ability PLGA vesicles was demonstrated in vitro by release of busulfan. PLGA vesicles degradation was studied in vitro, showing that approximately 32% was degraded into lactic and glycolic acid over a period of 5 weeks. The biodistribution of PLGA vesicles was investigated in vivo by MRI in a rat model. Change of contrast in the liver could be visualized by MRI after 7 min and maximal signal loss detected after 4 h post-injection of PLGA vesicles. Histological studies showed that the presence of PLGA vesicles in organs was shifted from the lungs to the liver and spleen over time.

Keywords: biodegradable polymers, multifunctional nanoparticles, quantum dots, anticancer drugs

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Authors: Nur Inayah Ismaniar, Sukri Palutturi, Ansariadi, Atjo Wahyu

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Background: In various countries in the world, the problem of smoking is now considered something serious because of the effects of smoking which can not only lead to addiction but also have the potential to harm health. Public health authorities have concluded that one solution that can be done to protect the public from active smokers is to issue a policy that requires public facilities to be completely smoke-free. The hospital is one of the public facilities that has been designated as a smoke-free area. However, the implementation and maintenance of a successful program based on a smoke-free hospital are still considered an ongoing challenge worldwide due to the very low level of adherence. The low level of compliance with this smoke-free policy is also seen in other public facilities. The purpose of the literature review is to review the level of compliance with the application of the Non-Smoking Area policy, how this policy has succeeded in reducing smoking activity in hospitals, and what factors lead to such compliance in each country in the world. Methods: A literature review of articles was carried out on all types of research methods, both qualitative and quantitative. The sample is all subjects who are in the research location, which includes patients, staff and hospital visitors. Results: Various variations in the level of compliance were found in various kinds of literature. The literature with the highest level of compliance is 88.4%. Furthermore, several determinants that are known to affect the compliance of the Non-Smoking Area policies in hospitals include communication, information, knowledge, perceptions, interventions, attitudes and support. Obstacles to its enforcement are the absence of sanctions against violators of the Non-Smoking Area policy, the ineffectiveness of the function of policymakers in hospitals, and negative perceptions of smoking related to mental health. Conclusion: Violations of the Non-Smoking Area policy are often committed by the hospital staff themselves, which makes it difficult for this policy to be fully enforced at various points in the hospital.

Keywords: health policy, non-smoking area, hospital, implementation

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Authors: Gurleen Kour, Mowkshi Khullar, B. K. Chandan, Parvinder Pal Singh, Kushalava Reddy Yumpalla, Gurunadham Munagala, Ram A. Vishwakarma, Zabeer Ahmed

Abstract:

New chemotherapeutic compounds against multidrug-resistant Mycobacterium tuberculosis (Mtb) are urgently needed to combat drug resistance in tuberculosis (TB). Apart from in-vitro potency against the target, physiochemical properties and pharmacokinetic properties play an imperative role in the process of drug discovery. We have identified novel nitroimidazole derivatives with potential activity against mycobacterium tuberculosis. One lead candidates, MCD-017, which showed potent activity against H37Rv strain (MIC=0.5µg/ml) and was further evaluated in the process of drug development. Methods: Basic physicochemical parameters like solubility and lipophilicity (LogP) were evaluated. Thermodynamic solubility was determined in PBS buffer (pH 7.4) using LC/MS-MS. The partition coefficient (Log P) of the compound was determined between octanol and phosphate buffered saline (PBS at pH 7.4) at 25°C by the microscale shake flask method. The compound followed Lipinski’s rule of five, which is predictive of good oral bioavailability and was further evaluated for metabolic stability. In-vitro metabolic stability was determined in rat liver microsomes. The hepatotoxicity of the compound was also determined in HepG2 cell line. In vivo pharmacokinetic profile of the compound after oral dosing was also obtained using balb/c mice. Results: The compound exhibited favorable solubility and lipophilicity. The physical and chemical properties of the compound were made use of as the first determination of drug-like properties. The compound obeyed Lipinski’s rule of five, with molecular weight < 500, number of hydrogen bond donors (HBD) < 5 and number of hydrogen bond acceptors(HBA) not more then 10. The log P of the compound was less than 5 and therefore the compound is predictive of exhibiting good absorption and permeation. Pooled rat liver microsomes were prepared from rat liver homogenate for measuring the metabolic stability. 99% of the compound was not metabolized and remained intact. The compound did not exhibit cytoxicity in hepG2 cells upto 40 µg/ml. The compound revealed good pharmacokinetic profile at a dose of 5mg/kg administered orally with a half life (t1/2) of 1.15 hours, Cmax of 642ng/ml, clearance of 4.84 ml/min/kg and a volume of distribution of 8.05 l/kg. Conclusion : The emergence of multi drug resistance (MDR) and extensively drug resistant (XDR) Tuberculosis emphasize the requirement of novel drugs active against tuberculosis. Thus, the need to evaluate physicochemical and pharmacokinetic properties in the early stages of drug discovery is required to reduce the attrition associated with poor drug exposure. In summary, it can be concluded that MCD-017 may be considered a good candidate for further preclinical and clinical evaluations.

Keywords: mycobacterium tuberculosis, pharmacokinetics, physicochemical properties, hepatotoxicity

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Authors: A. H. A. Hamid, N. A. Zainuddin, M. Y. M. Nor

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Millions of child refugees leave their countries in the hope of better and safer lives particularly in the aspect of education. However, the education access for the child refugees is strongly depending on the policies made by the federal and local governments. Malaysia, in particular, is a country which does not have a specific educational policy that is inclusive of child refugees. Hence, this study explores the feasibility of possible educational policy that specifically caters the needs of child refugees in Malaysia. These are preliminary findings of a case study which involved thirty-five postgraduate students in a local university who undertook Educational Policy coursework and five teachers in a refugee community centre in Kuala Lumpur, Malaysia. Interviews were recorded, transcribed and thematically analysed in relation to issues highlighted in the refugee education literature. The findings showed that most of the informants felt there is an urgent need of a systematic intervention put in place by the local government to cater to the needs of equal education access to the child refugees. A further large scale study is needed in the near future by integrating different perspectives of relevant stakeholders for an effective, efficient and sustainable policy formulation and implementation related to child refugees in Malaysia. The findings may be of interests to the educators, the ministry of education, state education office, district education office, teachers, parents and surrounding communities for their awareness about the needs of refugee education and the feasibility of educational policy for child refugees in the country.

Keywords: child refugees, educational policy, inclusive education, Malaysia

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Authors: R. Henry, H. Andriamboavonjy, J. B. Paulin, S. Drahy, R. Gourichon

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During past decade, Chinese monetary policy has been to maintain stability of exchange rate CNY/USD by creating parity between the two currencies. This policy, against market equilibrium, impacts the exchange rate in having low Yuan currency, and keeping attractiveness of Chinese industries. Using macroeconomic and statistic approach, the impact of such policy onto CNY/USD exchange rate is quantitatively determined. It is also pointed out how Chinese banks respect Basel III ratios, in particular the foreign exchange ratio. The main analysis is focusing on how Chinese banks will respect these ratios in the future.

Keywords: macroeconomics models, yuan floating exchange rate, basel iii, china banking system

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Authors: Neelam Rashid, Muhammad Zafar, Mushtaq Ahmad, Khafsa Malik, Syed Nasar Shah

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The present study was conducted to study the role of medicinal plants used to cure different ailments in Azad Kashmir. Various ethno medicinal surveys were carried out during 2016 to enlist the uses of plants against various ailments by rural communities of the area. Information was obtained from 60 local people including 45 males (10 traditional health practitioners) and 15 females by semi structured interviews and group discussions. 65 plant species belonging to 45 families were reported. The dominant plant habit was herbaceous (56%) while decoction was the most common method of utilization (40%). The most cited turmoil was the gastrointestinal disorders. The data obtained were analyzed using ethno medicinal indices such as FL, UV, ICF, FC, and RFC. Results revealed that various species had numerous uses in curing of diseases. So conservation of biodiversity of these medicinal plants and traditional knowledge can play important role in improving the local health conditions of rural people and modern drug discovery and development.

Keywords: medicinal plants, ailments, drug, health, traditional

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Authors: Momen Yaseen M. Amin

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Despite widespread coverage of language policy in the literature, there has been scant research probing into English language education policy at tertiary levels in general and in the case of higher education context of Iraqi Kurdistan in particular. The present qualitative study investigated the results of a questionnaire on attitudes toward English language education policy in terms of attitudes toward the English language in general, the current English education policy, and the purposes for learning English among Kurdish EFL university students. Moreover, this study aimed to investigate this topic in light of the participants’ gender and major. To this end, an adapted version of Yang’s (2012) questionnaire was administered to university EFL students majoring in soft and hard sciences (N=300, male 34%, female 67%, four and two disciplines, respectively) at two-state and private universities in Iraqi Kurdistan. The findings revealed positive attitudes toward English as an international language in both soft and hard sciences. While strongly subscribing to the idea that all Iraqi Kurdish students should learn the English language and the courses to be offered in English as well as Kurdish, the majority of the participants expressed their readiness and enthusiasm to excel in English and considered such competency a significant academic accomplishment. However, a good number felt dissatisfied with the status quo of English education at their institutions. This paper provides some implications and recommendations for English education policies makers, administrators, and English language instructors at tertiary levels.

Keywords: attitudes, language policy, English language education, Iraqi Kurdistan

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Authors: Kumaran Letchmanan, Shou-Cang Shen, Wai Kiong Ng

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Postoperative implant-associated infections in soft tissues and bones remain a serious complication in orthopaedic surgery, which leads to impaired healing, re-implantation, prolong hospital stay and increase cost. Drug-loaded implants with sustained release of antibiotics at the local site are current research interest to reduce the risk of post-operative infections and osteomyelitis, thus, minimize the need for follow-up care and increase patient comfort. However, the improved drug release of the drug-loaded bone cements is usually accompanied by a loss in mechanical strength, which is critical for weight-bearing bone cement. Recently, more attempts have been undertaken to develop techniques to enhance the antibiotic elution as well as preserve the mechanical properties of the bone cements. The present study investigates the potential influence of addition of mesoporous silica nanoparticles (MSN) on the in vitro drug release kinetics of gentamicin (GTMC), along with the mechanical properties of bone cements. Simplex P was formulated with MSN and loaded with GTMC by direct impregnation. Meanwhile, Simplex P with water soluble poragen (xylitol) and high loading of GTMC as well as commercial bone cement CMW Smartset GHV were used as controls. MSN-formulated bone cements are able to increase the drug release of GTMC by 3-fold with a cumulative release of more than 46% as compared with other control groups. Furthermore, a sustained release could be achieved for two months. The loaded nano-sized MSN with uniform pore channels significantly build up an effective nano-network path in the bone cement facilitates the diffusion and extended release of GTMC. Compared with formulations using xylitol and high GTMC loading, incorporation of MSN shows no detrimental effect on biomechanical properties of the bone cements as no significant changes in the mechanical properties as compared with original bone cement. After drug release for two months, the bending modulus of MSN-formulated bone cements is 4.49 ± 0.75 GPa and the compression strength is 92.7 ± 2.1 MPa (similar to the compression strength of Simplex-P: 93.0 ± 1.2 MPa). The unaffected mechanical properties of MSN-formulated bone cements was due to the unchanged microstructures of bone cement, whereby more than 98% of MSN remains in the matrix and supports the bone cement structures. In contrast, the large portions of extra voids can be observed for the formulations using xylitol and high drug loading after the drug release study, thus caused compressive strength below the ASTM F541 and ISO 5833 minimum of 70 MPa. These results demonstrate the potential applicability of MSN-functionalized poly(methyl methacrylate)-based bone cement as a highly efficient, sustained and local drug delivery system with good mechanical properties.

Keywords: antibiotics, biomechanical properties, bone cement, sustained release

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Authors: Mary Konadu

Abstract:

The rectal route for drug administration is becoming attractive to drug formulators because it can avoid hepatic first-pass effects, decrease gastrointestinal side effects and avoid undesirable effects of meals on drug absorption. Suppositories have been recognized as an alternative to the oral route in situations such as when the patient is comatose, unable to swallow, or when the drug produces nausea or vomiting. Effective drug delivery with appropriate pharmaceutical excipient is key in the production of clinically useful preparations. The high cost of available excipients coupled with other disadvantages have led to the exploration of potential excipients from natural sources. Allanblackia floribunda butter, a naturally occurring lipid, is used for medicinal, culinary, and cosmetic purposes. Different extraction methods (solvent (hexane) extraction, traditional/hot water extraction, and cold/screw press extraction) were employed to extract the oil. The different extracts of A. floribunda oil were analyzed for their physicochemical properties and mineral content. The oil was used as a base to formulate Paracetamol and Diclofenac suppositories. Quality control test were carried out on the formulated suppositories. The %age oil yield for hexane extract, hot water extract, and cold press extract were 50.40 ±0.00, 37.36±0.00, and 20.48±0.00, respectively. The acid value, saponification value, iodine value and free fatty acid were 1.159 ± 0.065, 208.51 ± 8.450, 49.877 ± 0.690 and 0.583 ± 0.032 respectively for hexane extract; 3.480 ± 0.055, 204.672±2.863, 49.04 ± 0.76 and 1.747 ± 0.028 respectively for hot water/traditional extract; 4.43 ± 0.055, 192.05±1.56, 49.96 ± 0.29 and 2.23 ± 0.03 respectively for cold press extract. Calcium, sodium, magnesium, potassium, and iron were minerals found to be present in the A. floribunda butter extracts. The uniformity of weight, hardness, disintegration time, and uniformity of content were found to be within the acceptable range. The melting point ranges for all the suppositories were found to be satisfactory. The cumulative drug release (%) of the suppositories at 45 minutes was 90.19±0.00 (Hot water extract), 93.75±0.00 (Cold Pres Extract), and 98.16±0.00 (Hexane Extract) for Paracetamol suppositories. Diclofenac sodium suppositories had a cumulative %age release of 81.60±0.00 (Hot water Extract), 95.33±0.00 (Cold Press Extract), and 99.20±0.00 (Hexane Extract). The physicochemical parameters obtained from this study shows that Allanblackia floribunda seed oil is edible and can be used as a suppository base. The suppository formulation was successful, and the quality control tests conformed to Pharmacopoeia standard.

Keywords: allanblackia foribunda, paracetamol, diclofenac, suppositories

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