Search results for: controlled drug delivery
4946 Abridging Pharmaceutical Analysis and Drug Discovery via LC-MS-TOF, NMR, in-silico Toxicity-Bioactivity Profiling for Therapeutic Purposing Zileuton Impurities: Need of Hour
Authors: Saurabh B. Ganorkar, Atul A. Shirkhedkar
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The need for investigations protecting against toxic impurities though seems to be a primary requirement; the impurities which may prove non - toxic can be explored for their therapeutic potential if any to assist advanced drug discovery. The essential role of pharmaceutical analysis can thus be extended effectively to achieve it. The present study successfully achieved these objectives with characterization of major degradation products as impurities for Zileuton which has been used for to treat asthma since years. The forced degradation studies were performed to identify the potential degradation products using Ultra-fine Liquid-chromatography. Liquid-chromatography-Mass spectrometry (Time of Flight) and Proton Nuclear Magnetic Resonance Studies were utilized effectively to characterize the drug along with five major oxidative and hydrolytic degradation products (DP’s). The mass fragments were identified for Zileuton and path for the degradation was investigated. The characterized DP’s were subjected to In-Silico studies as XP Molecular Docking to compare the gain or loss in binding affinity with 5-Lipooxygenase enzyme. One of the impurity of was found to have the binding affinity more than the drug itself indicating for its potential to be more bioactive as better Antiasthmatic. The close structural resemblance has the ability to potentiate or reduce bioactivity and or toxicity. The chances of being active biologically at other sites cannot be denied and the same is achieved to some extent by predictions for probability of being active with Prediction of Activity Spectrum for Substances (PASS) The impurities found to be bio-active as Antineoplastic, Antiallergic, and inhibitors of Complement Factor D. The toxicological abilities as Ames-Mutagenicity, Carcinogenicity, Developmental Toxicity and Skin Irritancy were evaluated using Toxicity Prediction by Komputer Assisted Technology (TOPKAT). Two of the impurities were found to be non-toxic as compared to original drug Zileuton. As the drugs are purposed and repurposed effectively the impurities can also be; as they can have more binding affinity; less toxicity and better ability to be bio-active at other biological targets.Keywords: UFLC, LC-MS-TOF, NMR, Zileuton, impurities, toxicity, bio-activity
Procedia PDF Downloads 1944945 Development of Methotrexate Nanostructured Lipid Carriers for Topical Treatment of Psoriasis: Optimization, Evaluation, and in vitro Studies
Authors: Yogeeta O. Agrawal, Hitendra S. Mahajan, Sanjay J. Surana
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Methotrexate is effective in controlling recalcitrant psoriasis when administered by the oral or parenteral route long-term. However, the systematic use of this drug may provoke any of a number of side effects, notably hepatotoxic effects. To reduce these effects, clinical studies have been done with topical MTx. It is useful in treating a number of cutaneous conditions, including psoriasis. A major problem in topical administration of MTx currently available in market is that the drug is hydrosoluble and is mostly in the dissociated form at physiological pH. Its capacity for passive diffusion is thus limited. Localization of MTx in effected layers of skin is likely to improve the role of topical dosage form of the drug as a supplementary to oral therapy for treatment of psoriasis. One of the possibilities for increasing the penetration of drugs through the skin is the use of Nanostructured lipid Carriers. The objective of the present study was to formulate and characterize Methotrexate loaded Nanostructured Lipid Carriers (MtxNLCs), to understand in vitro drug release and evaluate the role of the developed gel in the topical treatment of psoriasis. MtxNLCs were prepared by solvent diffusion technique using 3(2) full factorial design.The mean diameter and surface morphology of MtxNLC was evaluated. MtxNLCs were lyophilized and crystallinity of NLC was characterized by Differential Scanning Calorimtery (DSC) and powder X-Ray Diffraction (XRD). The NLCs were incorporated in 1% w/w Carbopol 934 P gel base and in vitro skin deposition studies in Human Cadaver Skin were conducted. The optimized MtxNLCs were spherical in shape, with average particle size of 253(±9.92)nm, zeta potential of -30.4 (±0.86) mV and EE of 53.12(±1.54)%. DSC and XRD data confirmed the formation of NLCs. Significantly higher deposition of Methotrexate was found in human cadaver skin from MtxNLC gel (71.52 ±1.23%) as compared to Mtx plain gel (54.28±1.02%). Findings of the studies suggest that there is significant improvement in therapeutic index in treatment of psoriasis by MTx-NLCs incorporated gel base developed in this investigation over plain drug gel currently available in the market.Keywords: methotrexate, psoriasis, NLCs, hepatotoxic effects
Procedia PDF Downloads 4304944 Physicochemical and Biological Characterization of 1,2-Dialkoylamidopropane-Based Lipoplexes for Gene Delivery
Authors: Suhair Saleh, Ahmad Aljaberi
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Cationic lipid-mediated delivery of nucleic acids represents an exciting approach for developing therapeutically realistic gene medicines. Elucidation of the molecular and formulation requirements for efficient lipofection is a prerequisite to enhance the biological activity of such delivery systems. To this end, the in vitro lipofection activity of the ionizable asymmetric 1,2-dialkoylamidopropane-based derivatives bearing single primary amine group as the cationic head group was evaluated. The electrostatic interactions of these cationic lipids with plasmid DNA in physiologically relevant medium were investigated by means of gel electrophoresis retardation and Eth-Br quenching assays. The effect of the presence of the helper lipid on these interactions was evaluated. The physicochemical properties of these lipids in terms of bilayer fluidity and extent of ionization were investigated using fluorescence anisotropy and surface potential techniques, respectively. The results showed that only the active lipid, 1,2lmp[5], existed in a liquid crystalline state at physiological temperature. Moreover, the extent of ionization of this lipid in assemblies was significantly higher that it's saturated analogues. Inclusion of the helper lipid DOPE improved the encapsulation and association between 1,2lmp[5] and plasmid DNA, which was reflected by the significant boost of lipofection activity of the 1,2lmp[5]/DOPE formulation as compared to the lipid alone. In conclusion, membrane fluidity and sufficient protonation of ionizable cationic lipid are required for efficient association and encapsulation of plasmid DNA and promoting improved in vitro lipofection activity.Keywords: cationic lipids, gene delivery, lipofection, membrane fluidity, helper lipids, surface potential
Procedia PDF Downloads 2424943 Northern Nigeria Vaccine Direct Delivery System
Authors: Evelyn Castle, Adam Thompson
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Background: In 2013, the Kano State Primary Health Care Management Board redesigned its Routine immunization supply chain from diffused pull to direct delivery push. It addressed issues around stockouts and reduced time spent by health facility staff collecting, and reporting on vaccine usage. The health care board sought the help of a 3PL for twice-monthly deliveries from its cold store to 484 facilities across 44 local governments. eHA’s Health Delivery Systems group formed a 3PL to serve 326 of these new facilities in partnership with the State. We focused on designing and implementing a technology system throughout. Basic methodologies: GIS Mapping: - Planning the delivery of vaccines to hundreds of health facilities requires detailed route planning for delivery vehicles. Mapping the road networks across Kano and Bauchi with a custom routing tool provided information for the optimization of deliveries. Reducing the number of kilometers driven each round by 20%, - reducing cost and delivery time. Direct Delivery Information System: - Vaccine Direct Deliveries are facilitated through pre-round planning (driven by health facility database, extensive GIS, and inventory workflow rules), manager and driver control panel customizing delivery routines and reporting, progress dashboard, schedules/routes, packing lists, delivery reports, and driver data collection applications. Move: Last Mile Logistics Management System: - MOVE has improved vaccine supply information management to be timely, accurate and actionable. Provides stock management workflow support, alerts management for cold chain exceptions/stock outs, and on-device analytics for health and supply chain staff. Software was built to be offline-first with user-validated interface and experience. Deployed to hundreds of vaccine storage site the improved information tools helps facilitate the process of system redesign and change management. Findings: - Stock-outs reduced from 90% to 33% - Redesigned current health systems and managing vaccine supply for 68% of Kano’s wards. - Near real time reporting and data availability to track stock. - Paperwork burdens of health staff have been dramatically reduced. - Medicine available when the community needs it. - Consistent vaccination dates for children under one to prevent polio, yellow fever, tetanus. - Higher immunization rates = Lower infection rates. - Hundreds of millions of Naira worth of vaccines successfully transported. - Fortnightly service to 326 facilities in 326 wards across 30 Local Government areas. - 6,031 cumulative deliveries. - Over 3.44 million doses transported. - Minimum travel distance covered in a round of delivery is 2000 kms & maximum of 6297 kms. - 153,409 kms travelled by 6 drivers. - 500 facilities in 326 wards. - Data captured and synchronized for the first time. - Data driven decision making now possible. Conclusion: eHA’s Vaccine Direct delivery has met challenges in Kano and Bauchi State and provided a reliable delivery service of vaccinations that ensure t health facilities can run vaccination clinics for children under one. eHA uses innovative technology that delivers vaccines from Northern Nigerian zonal stores straight to healthcare facilities. Helped healthcare workers spend less time managing supplies and more time delivering care, and will be rolled out nationally across Nigeria.Keywords: direct delivery information system, health delivery system, GIS mapping, Northern Nigeria, vaccines
Procedia PDF Downloads 3734942 Construction of Ovarian Cancer-on-Chip Model by 3D Bioprinting and Microfluidic Techniques
Authors: Zakaria Baka, Halima Alem
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Cancer is a major worldwide health problem that has caused around ten million deaths in 2020. In addition, efforts to develop new anti-cancer drugs still face a high failure rate. This is partly due to the lack of preclinical models that recapitulate in-vivo drug responses. Indeed conventional cell culture approach (known as 2D cell culture) is far from reproducing the complex, dynamic and three-dimensional environment of tumors. To set up more in-vivo-like cancer models, 3D bioprinting seems to be a promising technology due to its ability to achieve 3D scaffolds containing different cell types with controlled distribution and precise architecture. Moreover, the introduction of microfluidic technology makes it possible to simulate in-vivo dynamic conditions through the so-called “cancer-on-chip” platforms. Whereas several cancer types have been modeled through the cancer-on-chip approach, such as lung cancer and breast cancer, only a few works describing ovarian cancer models have been described. The aim of this work is to combine 3D bioprinting and microfluidic technics with setting up a 3D dynamic model of ovarian cancer. In the first phase, alginate-gelatin hydrogel containing SKOV3 cells was used to achieve tumor-like structures through an extrusion-based bioprinter. The desired form of the tumor-like mass was first designed on 3D CAD software. The hydrogel composition was then optimized for ensuring good and reproducible printability. Cell viability in the bioprinted structures was assessed using Live/Dead assay and WST1 assay. In the second phase, these bioprinted structures will be included in a microfluidic device that allows simultaneous testing of different drug concentrations. This microfluidic dispositive was first designed through computational fluid dynamics (CFD) simulations for fixing its precise dimensions. It was then be manufactured through a molding method based on a 3D printed template. To confirm the results of CFD simulations, doxorubicin (DOX) solutions were perfused through the dispositive and DOX concentration in each culture chamber was determined. Once completely characterized, this model will be used to assess the efficacy of anti-cancer nanoparticles developed in the Jean Lamour institute.Keywords: 3D bioprinting, ovarian cancer, cancer-on-chip models, microfluidic techniques
Procedia PDF Downloads 1964941 Polymer-Nanographite Nanocomposites for Biosensor Applications
Authors: Payal Mazumdar, Sunita Rattan, Monalisa Mukherjee
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Polymer nanocomposites are a special class of materials having unique properties and wide application in diverse areas such as EMI shielding, sensors, photovoltaic cells, membrane separation properties, drug delivery etc. Recently the nanocomposites are being investigated for their use in biomedical fields as biosensors. Though nanocomposites with carbon nanoparticles have received worldwide attention in the past few years, comparatively less work has been done on nanographite although it has in-plane electrical, thermal and mechanical properties comparable to that of carbon nanotubes. The main challenge in the fabrication of these nanocomposites lies in the establishment of homogeneous dispersion of nanographite in polymer matrix. In the present work, attempts have been made to synthesize the nanocomposites of polystyrene and nanographite using click chemistry. The polymer and the nanographite are functionalized prior to the formation of nanocomposites. The polymer, polystyrene, was functionalized with alkyne moeity and nanographite with azide moiety. The fabricating of the nanocomposites was accomplished through click chemistry using Cu (I)-catalyzed Huisgen dipolar cycloaddition. The functionalization of filler and polymer was confirmed by NMR and FTIR. The nanocomposites formed by the click chemistry exhibit better electrical properties and the sensors are evaluated for their application as biosensors.Keywords: nanocomposites, click chemistry, nanographite, biosensor
Procedia PDF Downloads 3064940 Ibrutinib and the Potential Risk of Cardiac Failure: A Review of Pharmacovigilance Data
Authors: Abdulaziz Alakeel, Roaa Alamri, Abdulrahman Alomair, Mohammed Fouda
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Introduction: Ibrutinib is a selective, potent, and irreversible small-molecule inhibitor of Bruton's tyrosine kinase (BTK). It forms a covalent bond with a cysteine residue (CYS-481) at the active site of Btk, leading to inhibition of Btk enzymatic activity. The drug is indicated to treat certain type of cancers such as mantle cell lymphoma (MCL), chronic lymphocytic leukaemia and Waldenström's macroglobulinaemia (WM). Cardiac failure is a condition referred to inability of heart muscle to pump adequate blood to human body organs. There are multiple types of cardiac failure including left and right-sided heart failure, systolic and diastolic heart failures. The aim of this review is to evaluate the risk of cardiac failure associated with the use of ibrutinib and to suggest regulatory recommendations if required. Methodology: Signal Detection team at the National Pharmacovigilance Center (NPC) of Saudi Food and Drug Authority (SFDA) performed a comprehensive signal review using its national database as well as the World Health Organization (WHO) database (VigiBase), to retrieve related information for assessing the causality between cardiac failure and ibrutinib. We used the WHO- Uppsala Monitoring Centre (UMC) criteria as standard for assessing the causality of the reported cases. Results: Case Review: The number of resulted cases for the combined drug/adverse drug reaction are 212 global ICSRs as of July 2020. The reviewers have selected and assessed the causality for the well-documented ICSRs with completeness scores of 0.9 and above (35 ICSRs); the value 1.0 presents the highest score for best-written ICSRs. Among the reviewed cases, more than half of them provides supportive association (four probable and 15 possible cases). Data Mining: The disproportionality of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by WHO-UMC to measure the reporting ratio. Positive IC reflects higher statistical association while negative values indicates less statistical association, considering the null value equal to zero. The results of (IC=1.5) revealed a positive statistical association for the drug/ADR combination, which means “Ibrutinib” with “Cardiac Failure” have been observed more than expected when compared to other medications available in WHO database. Conclusion: Health regulators and health care professionals must be aware for the potential risk of cardiac failure associated with ibrutinib and the monitoring of any signs or symptoms in treated patients is essential. The weighted cumulative evidences identified from causality assessment of the reported cases and data mining are sufficient to support a causal association between ibrutinib and cardiac failure.Keywords: cardiac failure, drug safety, ibrutinib, pharmacovigilance, signal detection
Procedia PDF Downloads 1294939 Assessing the Informed Consent Practices during Normal Vaginal Delivery Process and Immediate Postpartum Care in Tertiary Level Hospitals of Bangladesh
Authors: Md. Abdul Karim, Syed Imran Ahmed, Pandora T. Hardtman
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Informed consent is one of the basic human and ethical rights for childbearing women. It plays a central role in promoting informed decision making between patients and service providers during the labor process. It gives mothers rights to accept or reject any examination and/or procedure, increases the respect and dignity of the mother during pregnancy, delivery and postpartum care. To assess the practices of this right during normal vaginal delivery and immediate postpartum care in tertiary level hospital setting in Bangladesh, a quantitative study with cross-sectional design was conducted in Dhaka Medical College & Hospital (DMCH) and Sir Salimullah Medical College & Mitford Hospital (SSMCH) in Dhaka in November 2015. A prevalence-based sample size of 190 was calculated where prevalence, confidence interval and level of significance were at 9.7%, 98% and 5% respectively. The respondents were the mothers who gave normal vaginal childbirth within past 24 hours and received postpartum care there. They were selected through systematic random sampling technique and their face-to-face interview of 190 mothers was done using a structured questionnaire. Data were entered into the spreadsheet (MS Excel 2013 version) and descriptive analysis of findings was done. The result shows the complete absence of informed consent practices and mostly absence of consented care such as right to information, respect for choices of preferences for examination and/or procedure of childbearing women. Although 95% of the mothers were informed that they were being proceeded with normal vaginal delivery, their choice of preference was absent during the process. Only consent (not informed consent) was taken from 50%-72% mothers for examination (except breast examination ‘0%’) and 8%-83% for any procedures during postpartum care. Only one-ninth (11%) of the mothers could ask service providers regarding the services they received. No consent was taken from 3% of the mothers- neither in the labor process nor in postpartum care. This current practice doesn’t comply with the Respectful Maternity Care (RMC) Charter 2011. The issue is not even clarified in the current Standard Clinical Management Protocols of the country. So, improvement of the existing protocol and increased awareness are essential to address this right of child-bearing women and to practice it during normal vaginal delivery and postpartum care.Keywords: informed consent, normal vaginal delivery, respectful maternity care, tertiary level hospital
Procedia PDF Downloads 1584938 Screening for Non-hallucinogenic Neuroplastogens as Drug Candidates for the Treatment of Anxiety, Depression, and Posttraumatic Stress Disorder
Authors: Jillian M. Hagel, Joseph E. Tucker, Peter J. Facchini
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With the aim of establishing a holistic approach for the treatment of central nervous system (CNS) disorders, we are pursuing a drug development program rapidly progressing through discovery and characterization phases. The drug candidates identified in this program are referred to as neuroplastogens owing to their ability to mediate neuroplasticity, which can be beneficial to patients suffering from anxiety, depression, or posttraumatic stress disorder. These and other related neuropsychiatric conditions are associated with the onset of neuronal atrophy, which is defined as a reduction in the number and/or productivity of neurons. The stimulation of neuroplasticity results in an increase in the connectivity between neurons and promotes the restoration of healthy brain function. We have synthesized a substantial catalogue of proprietary indolethylamine derivatives based on the general structures of serotonin (5-hydroxytryptamine) and psychedelic molecules such as N,N-dimethyltryptamine (DMT) and psilocin (4-hydroxy-DMT) that function as neuroplastogens. A primary objective in our screening protocol is the identification of derivatives associated with a significant reduction in hallucination, which will allow administration of the drug at a dose that induces neuroplasticity and triggers other efficacious outcomes in the treatment of targeted CNS disorders but which does not cause a psychedelic response in the patient. Both neuroplasticity and hallucination are associated with engagement of the 5HT2A receptor, requiring drug candidates differentially coupled to these two outcomes at a molecular level. We use novel and proprietary artificial intelligence algorithms to predict the mode of binding to the 5HT2A receptor, which has been shown to correlate with the hallucinogenic response. Hallucination is tested using the mouse head-twitch response model, whereas mouse marble-burying and sucrose preference assays are used to evaluate anxiolytic and anti-depressive potential. Neuroplasticity is assays using dendritic outgrowth assays and cell-based ELISA analysis. Pharmacokinetics and additional receptor-binding analyses also contribute the selection of lead candidates. A summary of the program is presented.Keywords: neuroplastogen, non-hallucinogenic, drug development, anxiety, depression, PTSD, indolethylamine derivatives, psychedelic-inspired, 5-HT2A receptor, computational chemistry, head-twitch response behavioural model, neurite outgrowth assay
Procedia PDF Downloads 1384937 pH and Thermo-Sensitive Nanogels for Anti-Cancer Therapy
Authors: V. Naga Sravan Kumar Varma, H. G. Shivakumar
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The aim of the study was to develop dual sensitive poly (N-isopropylacrylamide-co-acrylic acid) (PNA) nanogels(NGs) and studying its applications for Anti-Cancer therapy. NGs were fabricated by free radical polymerization using different amount of N-isopropylacrylamide and acrylic acid. A study for polymer composition over the effect on LCST in different pH was evaluated by measuring the absorbance at 500nm using UV spectrophotometer. Further selected NG’s were evaluated for change in hydrodynamic diameters in response to pH and temperature. NGs which could sharply respond to low pH value of cancer cells at body temperature were loaded with Fluorouracil (5-FU) using equilibrium swelling method and studied for drug release behaviour in different pH. A significant influence of NGs polymer composition over pH dependent LCST was observed. NGs which were spherical with an average particle size of 268nm at room temperature, shrinked forming an irregular shape when heated above to their respective LCST. 5FU loaded NGs did not intervene any difference in pH depended LCST behaviour of NGs. The in vitro drug release of NGs exhibited a pH and thermo-dependent control release. The cytoxicity study of blank carrier to MCF7 cell line showed no cytotoxicity. The results indicated that PNA NGs could be used as a potential drug carrier for anti-cancer therapy.Keywords: pH and thermo-sensitive, nanogels, P(NIPAM-co-AAc), anti-cancer, 5-FU
Procedia PDF Downloads 3504936 Effectual Role of Local Level Partnership Schemes in Affordable Housing Delivery
Authors: Hala S. Mekawy
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Affordable housing delivery for low and lower middle income families is a prominent problem in many developing countries; governments alone are unable to address this challenge due to diverse financial and regulatory constraints, and the private sector's contribution is rare and assists only middle-income households even when institutional and legal reforms are conducted to persuade it to go down market. Also, the market-enabling policy measures advocated by the World Bank since the early nineties have been strongly criticized and proven to be inappropriate to developing country contexts, where it is highly unlikely that the formal private sector can reach low income population. In addition to governments and private developers, affordable housing delivery systems involve an intricate network of relationships between diverse ranges of actors. Collaboration between them was proven to be vital, and hence, an approach towards partnership schemes for affordable housing delivery has emerged. The basic premise of this paper is that addressing housing affordability challenges in Egypt demands direct public support, as markets and market actors alone would never succeed in delivering decent affordable housing to low and lower middle income groups. It argues that this support would ideally be through local level partnership schemes, with a leading decentralized local government role, and partners being identified according to specific local conditions. It attempts to identify major attributes that would ensure the fulfilment of the goals of such schemes in the Egyptian context. This is based upon evidence from diversified worldwide experiences, in addition to the main outcomes of a questionnaire that was conducted to specialists and chief actors in the field.Keywords: affordable housing, partnership schemes, housing, urban environments
Procedia PDF Downloads 2284935 Need of Medicines Information OPD in Tertiary Health Care Settings: A Cross Sectional Study
Authors: Swanand Pathak, Kiran R. Giri, Reena R. Giri, Kamlesh Palandurkar, Sangita Totade, Rajesh Jha, S. S. Patel
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Background: Population burden, illiteracy, availability of few doctors for larger group of population leads to many unanswered questions left in a patient’s mind. Incomplete information results into noncompliance, therapeutic failure, and adverse drug reactions (ADR). It is very important to establish a system which will provide noncommercial, independent, unbiased source of medicine information. Medicines Info OPD is a concept and step towards safe and appropriate use of medicines. Objective: (1) to assess the present status of knowledge about the medicines in the patients and its correlation with education; (2) to assess the medicine information dispensing modalities, their use and sufficiency from the patients view point; (3) to assess the overall need for Medicines Information OPD in present scenario. Materials and Methods: A pre-validated questionnaire based study was conducted amongst 500 patients of tertiary health care hospital. The questionnaire consisted of specific questions regarding understanding of prescription, knowledge about adverse drug reaction, view about self-medication and opinion regarding the need of Medicines Info OPD. Results: Significantly large proportion of patients opined that doctors do not have sufficient time in current Indian healthcare to explain the prescription and they are not aware of adverse drug reactions, expiry date or use the package inserts etc. Conclusion: Clinically relevant, up to date, user specific, independent, objective and unbiased Medicines Info OPD is essential for appropriate drug use and can help in a big way to common public to address many problems faced by them.Keywords: information, prescription, unbiased, clinically relevant
Procedia PDF Downloads 4424934 An Automated Magnetic Dispersive Solid-Phase Extraction Method for Detection of Cocaine in Human Urine
Authors: Feiyu Yang, Chunfang Ni, Rong Wang, Yun Zou, Wenbin Liu, Chenggong Zhang, Fenjin Sun, Chun Wang
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Cocaine is the most frequently used illegal drug globally, with the global annual prevalence of cocaine used ranging from 0.3% to 0.4 % of the adult population aged 15–64 years. Growing consumption trend of abused cocaine and drug crimes are a great concern, therefore urine sample testing has become an important noninvasive sampling whereas cocaine and its metabolites (COCs) are usually present in high concentrations and relatively long detection windows. However, direct analysis of urine samples is not feasible because urine complex medium often causes low sensitivity and selectivity of the determination. On the other hand, presence of low doses of analytes in urine makes an extraction and pretreatment step important before determination. Especially, in gathered taking drug cases, the pretreatment step becomes more tedious and time-consuming. So developing a sensitive, rapid and high-throughput method for detection of COCs in human body is indispensable for law enforcement officers, treatment specialists and health officials. In this work, a new automated magnetic dispersive solid-phase extraction (MDSPE) sampling method followed by high performance liquid chromatography-mass spectrometry (HPLC-MS) was developed for quantitative enrichment of COCs from human urine, using prepared magnetic nanoparticles as absorbants. The nanoparticles were prepared by silanizing magnetic Fe3O4 nanoparticles and modifying them with divinyl benzene and vinyl pyrrolidone, which possesses the ability for specific adsorption of COCs. And this kind of magnetic particle facilitated the pretreatment steps by electromagnetically controlled extraction to achieve full automation. The proposed device significantly improved the sampling preparation efficiency with 32 samples in one batch within 40mins. Optimization of the preparation procedure for the magnetic nanoparticles was explored and the performances of magnetic nanoparticles were characterized by scanning electron microscopy, vibrating sample magnetometer and infrared spectra measurements. Several analytical experimental parameters were studied, including amount of particles, adsorption time, elution solvent, extraction and desorption kinetics, and the verification of the proposed method was accomplished. The limits of detection for the cocaine and cocaine metabolites were 0.09-1.1 ng·mL-1 with recoveries ranging from 75.1 to 105.7%. Compared to traditional sampling method, this method is time-saving and environmentally friendly. It was confirmed that the proposed automated method was a kind of highly effective way for the trace cocaine and cocaine metabolites analyses in human urine.Keywords: automatic magnetic dispersive solid-phase extraction, cocaine detection, magnetic nanoparticles, urine sample testing
Procedia PDF Downloads 2044933 Therapeutic Drug Monitoring by Dried Blood Spot and LC-MS/MS: Novel Application to Carbamazepine and Its Metabolite in Paediatric Population
Authors: Giancarlo La Marca, Engy Shokry, Fabio Villanelli
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Epilepsy is one of the most common neurological disorders, with an estimated prevalence of 50 million people worldwide. Twenty five percent of the epilepsy population is represented in children under the age of 15 years. For antiepileptic drugs (AED), there is a poor correlation between plasma concentration and dose especially in children. This was attributed to greater pharmacokinetic variability than adults. Hence, therapeutic drug monitoring (TDM) is recommended in controlling toxicity while drug exposure is maintained. Carbamazepine (CBZ) is a first-line AED and the drug of first choice in trigeminal neuralgia. CBZ is metabolised in the liver into carbamazepine-10,11-epoxide (CBZE), its major metabolite which is equipotent. This develops the need for an assay able to monitor the levels of both CBZ and CBZE. The aim of the present study was to develop and validate a LC-MS/MS method for simultaneous quantification of CBZ and CBZE in dried blood spots (DBS). DBS technique overcomes many logistical problems, ethical issues and technical challenges faced by classical plasma sampling. LC-MS/MS has been regarded as superior technique over immunoassays and HPLC/UV methods owing to its better specificity and sensitivity, lack of interference or matrix effects. Our method combines advantages of DBS technique and LC-MS/MS in clinical practice. The extraction process was done using methanol-water-formic acid (80:20:0.1, v/v/v). The chromatographic elution was achieved by using a linear gradient with a mobile phase consisting of acetonitrile-water-0.1% formic acid at a flow rate of 0.50 mL/min. The method was linear over the range 1-40 mg/L and 0.25-20 mg/L for CBZ and CBZE respectively. The limit of quantification was 1.00 mg/L and 0.25 mg/L for CBZ and CBZE, respectively. Intra-day and inter-day assay precisions were found to be less than 6.5% and 11.8%. An evaluation of DBS technique was performed, including effect of extraction solvent, spot homogeneity and stability in DBS. Results from a comparison with the plasma assay are also presented. The novelty of the present work lies in being the first to quantify CBZ and its metabolite from only one 3.2 mm DBS disc finger-prick sample (3.3-3.4 µl blood) by LC-MS/MS in a 10 min. chromatographic run.Keywords: carbamazepine, carbamazepine-10, 11-epoxide, dried blood spots, LC-MS/MS, therapeutic drug monitoring
Procedia PDF Downloads 4174932 The Underestimation of Cultural Risk in the Execution of Megaprojects
Authors: Alan Walsh, Peter Walker, Michael Ellis
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There is a real danger that both practitioners and researchers considering risks associated with megaprojects ignore or underestimate the impacts of cultural risk. The paper investigates the potential impacts of a failure to achieve cultural unity between the principal actors executing a megaproject. The principle relationships include the relationships between the principle Contractors and the project stakeholders or the project stakeholders and their principle advisors, Western Consultants. This study confirms that cultural dissonance between these parties can delay or disrupt the megaproject execution and examines why cultural issues should be prioritized as a significant risk factor in megaproject delivery. This paper addresses the practical impacts and potential mitigation measures, which may reduce cultural dissonance for a megaproject's delivery. This information is retrieved from on-going case studies in live infrastructure megaprojects in Europe and the Middle East's GCC states, from Western Consultants' perspective. The collaborating researchers each have at least 30 years of construction experience and are engaged in architecture, project management and contracts management, dealing with megaprojects in Europe or the GCC. After examining the cultural interfaces they have observed during the execution of megaprojects, they conclude that globally, culture significantly influences their efficient delivery. The study finds that cultural risk is ever-present, where different nationalities co-manage megaprojects and that cultural conflict poses a real threat to the timely delivery of megaprojects. The study indicates that the higher the cultural distance between the principal actors, the more pronounced the risk, with the risk of cultural dissonance more prominent in GCC megaprojects. The findings support a more culturally aware and cohesive team approach and recommend cross-cultural training to mitigate the effects of cultural disparity.Keywords: cultural risk underestimation, cultural distance, megaproject characteristics, megaproject execution
Procedia PDF Downloads 1054931 Advancements in Autonomous Drones for Enhanced Healthcare Logistics
Authors: Bhaargav Gupta P., Vignesh N., Nithish Kumar R., Rahul J., Nivetha Ruvah D.
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Delivering essential medical supplies to rural and underserved areas is challenging due to infrastructure limitations and logistical barriers, often resulting in inefficiencies and delays. Traditional delivery methods are hindered by poor road networks, long distances, and difficult terrains, compromising timely access to vital resources, especially in emergencies. This paper introduces an autonomous drone system engineered to optimize last-mile delivery. By utilizing advanced navigation and object-detection algorithms, such as region-based convolutional neural networks (R-CNN), our drones efficiently avoid obstacles, identify safe landing zones, and adapt dynamically to varying environments. Equipped with high-precision GPS and autonomous capabilities, the drones effectively navigate complex, remote areas with minimal dependence on established infrastructure. The system includes a dedicated mobile application for secure order placement and real-time tracking, and a secure payload box with OTP verification ensures tamper-resistant delivery to authorized recipients. This project demonstrates the potential of automated drone technology in healthcare logistics, offering a scalable and eco-friendly approach to enhance accessibility and service delivery in underserved regions. By addressing logistical gaps through advanced automation, this system represents a significant advancement toward sustainable, accessible healthcare in remote areas.Keywords: region-based convolutional neural network, one time password, global positioning system, autonomous drones, healthcare logistics
Procedia PDF Downloads 74930 A Controlled Natural Language Assisted Approach for the Design and Automated Processing of Service Level Agreements
Authors: Christopher Schwarz, Katrin Riegler, Erwin Zinser
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The management of outsourcing relationships between IT service providers and their customers proofs to be a critical issue that has to be stipulated by means of Service Level Agreements (SLAs). Since service requirements differ from customer to customer, SLA content and language structures vary largely, standardized SLA templates may not be used and an automated processing of SLA content is not possible. Hence, SLA management is usually a time-consuming and inefficient manual process. For overcoming these challenges, this paper presents an innovative and ITIL V3-conform approach for automated SLA design and management using controlled natural language in enterprise collaboration portals. The proposed novel concept is based on a self-developed controlled natural language that follows a subject-predicate-object approach to specify well-defined SLA content structures that act as templates for customized contracts and support automated SLA processing. The derived results eventually enable IT service providers to automate several SLA request, approval and negotiation processes by means of workflows and business rules within an enterprise collaboration portal. The illustrated prototypical realization gives evidence of the practical relevance in service-oriented scenarios as well as the high flexibility and adaptability of the presented model. Thus, the prototype enables the automated creation of well defined, customized SLA documents, providing a knowledge representation that is both human understandable and machine processable.Keywords: automated processing, controlled natural language, knowledge representation, information technology outsourcing, service level management
Procedia PDF Downloads 4324929 Non-Medical Prescription and Other Drug Use in Relation to Mental Health and World Beliefs: A Study of College Students
Authors: Sarah P. Wuebbolt, Ashlee N. Sawyer-Mays
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Non-medical prescription and other drug (NMPOD) use has been a significant public health issue for the last few decades, with problematic use increasing among university students more recently. The current study focused on associations between NMPOD use and mental health, well-being, and world beliefs among young adults. Young adults (N=513) completed online questionnaires assessing stress, demographic characteristics, self-esteem, NMPOD use, coping mechanisms, and anxiety. A substantial portion of participants reported using cannabis (48.5%, n=249), while smaller portions of participants reported using stimulants (26.7%, n = 137), sedatives (17.2%, n=88), opioids (10.8%, n=55), and hallucinogens (14.4%, n=74). Five hierarchical logistic regressions were performed to determine the independent relationships between mental health, well-being, and world belief factors and NMPOD use for the five classes of substances. After controlling for demographic factors (age, gender, race/ethnicity, sexual orientation, and religious affiliation), depression was associated with increased non-medical stimulant, opioid, and cannabis use; coping self-efficacy was associated with increased hallucinogen use, and attendance of worship services was associated with decreased non-medical cannabis and hallucinogen use. Results suggest that depression was strongly associated with non-medical stimulant, opioid, and cannabis use, and attendance of worship services was protective against cannabis and hallucinogen use. To the best of our knowledge, this is one of the first studies to investigate the relationships between mental health, well-being, world beliefs, and NMPOD use among young adults. The present study illuminates future targets for intervention, such as increased access to mental health diagnosis and treatment and the exploration of the roles of religion and shared community in the prevention of drug use among young adults.Keywords: cannabis, mental health, non-medical prescription and other drug use, world beliefs
Procedia PDF Downloads 644928 Bioresorbable Medicament-Eluting Grommet Tube for Otitis Media with Effusion
Authors: Chee Wee Gan, Anthony Herr Cheun Ng, Yee Shan Wong, Subbu Venkatraman, Lynne Hsueh Yee Lim
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Otitis media with effusion (OME) is the leading cause of hearing loss in children worldwide. Surgery to insert grommet tube into the eardrum is usually indicated for OME unresponsive to antimicrobial therapy. It is the most common surgery for children. However, current commercially available grommet tubes are non-bioresorbable, not drug-treated, with unpredictable duration of retention on the eardrum to ventilate middle ear. Their functionality is impaired when clogged or chronically infected, requiring additional surgery to remove/reinsert grommet tubes. We envisaged that a novel fully bioresorbable grommet tube with sustained antibiotic release technology could address these drawbacks. In this study, drug-loaded bioresorbable poly(L-lactide-co-ε-caprolactone)(PLC) copolymer grommet tubes were fabricated by microinjection moulding technique. In vitro drug release and degradation model of PLC tubes were studied. Antibacterial property was evaluated by incubating PLC tubes with P. aeruginosa broth. Surface morphology was analyzed using scanning electron microscopy. A preliminary animal study was conducted using guinea pigs as an in vivo model to evaluate PLC tubes with and without drug, with commercial Mini Shah grommet tube as comparison. Our in vitro data showed sustained drug release over 3 months. All PLC tubes revealed exponential degradation profiles over time. Modeling predicted loss of tube functionality in water to be approximately 14 weeks and 17 weeks for PLC with and without drug, respectively. Generally, PLC tubes had less bacteria adherence, which were attributed to the much smoother tube surfaces compared to Mini Shah. Antibiotic from PLC tube further made bacteria adherence on surface negligible. They showed neither inflammation nor otorrhea after 18 weeks post-insertion in the eardrums of guinea pigs, but had demonstrated severe degree of bioresorption. Histology confirmed the new PLC tubes were biocompatible. Analyses on the PLC tubes in the eardrums showed bioresorption profiles close to our in vitro degradation models. The bioresorbable antibiotic-loaded grommet tubes showed good predictability in functionality. The smooth surface and sustained release technology reduced the risk of tube infection. Tube functional duration of 18 weeks allowed sufficient ventilation period to treat OME. Our ongoing studies include modifying the surface properties with protein coating, optimizing the drug dosage in the tubes to enhance their performances, evaluating their functional outcome on hearing after full resoption of grommet tube and healing of eardrums, and developing animal model with OME to further validate our in vitro models.Keywords: bioresorbable polymer, drug release, grommet tube, guinea pigs, otitis media with effusion
Procedia PDF Downloads 4504927 Optimal Control of DC Motor Using Linear Quadratic Regulator
Authors: Meetty Tomy, Arxhana G Thosar
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This paper provides the implementation of optimal control for an armature-controlled DC motor. The selection of error weighted Matrix and control weighted matrix in order to implement optimal control theory for improving the dynamic behavior of DC motor is presented. The closed loop performance of Armature controlled DC motor with derived linear optimal controller is then evaluated for the transient operating condition (starting). The result obtained from MATLAB is compared with that of PID controller and simple closed loop response of the motor.Keywords: optimal control, DC motor, performance index, MATLAB
Procedia PDF Downloads 4104926 Opioid Administration on Patients Hospitalized in the Emergency Department
Authors: Mani Mofidi, Neda Valizadeh, Ali Hashemaghaee, Mona Hashemaghaee, Soudabeh Shafiee Ardestani
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Background: Acute pain and its management remained the most complaint of emergency service admission. Diagnostic and therapeutic procedures add to patients’ pain. Diminishing the pain increases the quality of patient’s feeling and improves the patient-physician relationship. Aim: The aim of this study was to evaluate the outcomes and side effects of opioid administration in emergency patients. Material and Methods: patients admitted to ward II emergency service of Imam Khomeini hospital, who received one of the opioids: morphine, pethidine, methadone or fentanyl as an analgesic were evaluated. Their vital signs and general condition were examined before and after drug injection. Also, patient’s pain experience were recorded as numerical rating score (NRS) before and after analgesic administration. Results: 268 patients were studied. 34 patients were addicted to opioid drugs. Morphine had the highest rate of prescription (86.2%), followed by pethidine (8.5%), methadone (3.3%) and fentanyl (1.68). While initial NRS did not show significant difference between addicted patients and non-addicted ones, NRS decline and its score after drug injection were significantly lower in addicted patients. All patients had slight but statistically significant lower respiratory rate, heart rate, blood pressure and O2 saturation. There was no significant difference between different kind of opioid prescription and its outcomes or side effects. Conclusion: Pain management should be always in physicians’ mind during emergency admissions. It should not be assumed that an addicted patient complaining of pain is malingering to receive drug. Titration of drug and close monitoring must be in the curriculum to prevent any hazardous side effects.Keywords: numerical rating score, opioid, pain, emergency department
Procedia PDF Downloads 4264925 Ebola Virus Glycoprotein Inhibitors from Natural Compounds: Computer-Aided Drug Design
Authors: Driss Cherqaoui, Nouhaila Ait Lahcen, Ismail Hdoufane, Mehdi Oubahmane, Wissal Liman, Christelle Delaite, Mohammed M. Alanazi
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The Ebola virus is a highly contagious and deadly pathogen that causes Ebola virus disease. The Ebola virus glycoprotein (EBOV-GP) is a key factor in viral entry into host cells, making it a critical target for therapeutic intervention. Using a combination of computational approaches, this study focuses on the identification of natural compounds that could serve as potent inhibitors of EBOV-GP. The 3D structure of EBOV-GP was selected, with missing residues modeled, and this structure was minimized and equilibrated. Two large natural compound databases, COCONUT and NPASS, were chosen and filtered based on toxicity risks and Lipinski’s Rule of Five to ensure drug-likeness. Following this, a pharmacophore model, built from 22 reported active inhibitors, was employed to refine the selection of compounds with a focus on structural relevance to known Ebola inhibitors. The filtered compounds were subjected to virtual screening via molecular docking, which identified ten promising candidates (five from each database) with strong binding affinities to EBOV-GP. These compounds were then validated through molecular dynamics simulations to evaluate their binding stability and interactions with the target. The top three compounds from each database were further analyzed using ADMET profiling, confirming their favorable pharmacokinetic properties, stability, and safety. These results suggest that the selected compounds have the potential to inhibit EBOV-GP, offering new avenues for antiviral drug development against the Ebola virus.Keywords: EBOV-GP, Ebola virus glycoprotein, high-throughput drug screening, molecular docking, molecular dynamics, natural compounds, pharmacophore modeling, virtual screening
Procedia PDF Downloads 214924 Promoted Thermoelectric Properties of Polymers through Controlled Tie-Chain Incorporation
Authors: Wenjin Zhu, Ian E. Jacobs, Henning Sirringhaus
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We have demonstrated a model system for the controlled incorporation of tie-chains into semicrystalline conjugated polymers using blends of different molecular weights that leads to a significant increase in electrical conductivity. Through careful assessment of the microstructural evolution upon tie chain incorporation we have demonstrated that no major changes in phase morphology or structural order in the crystalline domains occur and that the observed enhancement in electrical conductivity can only be explained consistently by tie chains facilitating the transport across grain boundaries between the crystalline domains. Here we studied the thermoelectric properties of aligned, ion exchange-doped ribbon phase PBTTT with blends of different molecular weight components. We demonstrate that in blended films higher electrical conductivities (up to 4810.1 S/cm), Seebeck coefficients and thermoelectric power factors of up to 172.6 μW m-1 K-2 can be achieved than in films with single component molecular weights. We investigate the underpinning thermoelectric transport physics, including structural and spectroscopic characterization, to better understand how controlled tie chain incorporation can be used to enhance the thermoelectric performance of aligned conjugated polymers.Keywords: organic electronics, thermoelectrics, conjugated polymers, tie chain
Procedia PDF Downloads 634923 Efficacy and Safety of Sublingual Sufentanil for the Management of Acute Pain
Authors: Neil Singla, Derek Muse, Karen DiDonato, Pamela Palmer
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Introduction: Pain is the most common reason people visit emergency rooms. Studies indicate however, that Emergency Department (ED) physicians often do not provide adequate analgesia to their patients as a result of gender and age bias, opiophobia and insufficient knowledge of and formal training in acute pain management. Novel classes of analgesics have recently been introduced, but many patients suffer from acute pain in settings where the availability of intravenous (IV) access may be limited, so there remains a clinical need for rapid-acting, potent analgesics that do not require an invasive route of delivery. A sublingual sufentanil tablet (SST), dispensed using a single-dose applicator, is in development for treatment of moderate-to-severe acute pain in a medically-supervised setting. Objective: The primary objective of this study was to demonstrate the repeat-dose efficacy, safety and tolerability of sufentanil 20 mcg and 30 mcg sublingual tablets compared to placebo for the management of acute pain as determined by the time-weighted sum of pain intensity differences (SPID) to baseline over the 12-hour study period (SPID12). Key secondary efficacy variables included SPID over the first hour (SPID1), Total pain relief over the 12-hour study period (TOTPAR12), time to perceived pain relief (PR) and time to meaningful PR. Safety variables consisted of adverse events (AE), vital signs, oxygen saturation and early termination. Methods: In this Phase 2, double-blind, dose-finding study, an equal number of male and female patients were randomly assigned in a 2:2:1 ratio to SST 20 mcg, SS 30 mcg or placebo, respectively, following bunionectomy. Study drug was dosed as needed, but not more frequently than hourly. Rescue medication was available as needed. The primary endpoint was the Summed Pain Intensity Difference to baseline over 12h (SPIDI2). Safety was assessed by continuous oxygen saturation monitoring and adverse event reporting. Results: 101 patients (51 Male/50 Female) were randomized, 100 received study treatment (intent-to-treat [ITT] population), and 91 completed the study. Reasons for early discontinuation were lack of efficacy (6), adverse events (2) and drug-dosing error (1). Mean age was 42.5 years. For the ITT population, SST 30 mcg was superior to placebo (p=0.003) for the SPID12. SPID12 scores in the active groups were superior for both male (ANOVA overall p-value =0.038) and female (ANOVA overall p-value=0.005) patients. Statistically significant differences in favour of sublingual sufentanil were also observed between the SST 30mcg and placebo group for SPID1(p<0.001), TOTPAR12(p=0.002), time to perceived PR (p=0.023) and time to meaningful PR (p=0.010). Nausea, vomiting and somnolence were more frequent in the sufentanil groups but there were no significant differences between treatment arms for the proportion of patients who prematurely terminated due to AE or inadequate analgesia. Conclusions: Sufentanil tablets dispensed sublingually using a single-dose applicator is in development for treatment of patients with moderate-to-severe acute pain in a medically-supervised setting where immediate IV access is limited. When administered sublingually, sufentanil’s pharmacokinetic profile and non-invasive delivery makes it a useful alternative to IM or IV dosing.Keywords: acute pain, pain management, sublingual, sufentanil
Procedia PDF Downloads 3564922 Combined Orthodontic and Restorative Management of Complex Cases: Concepts and Case Reports
Authors: Awais Ali, Hesham Ali
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The absence of teeth through either premature loss or developmental absence is a common condition with potentially severe impact on affected individuals. Management of these cases presents a clinical challenge which may be difficult to resolve given the effects of tooth loss or hypodontia over the course of a patient’s lifetime. Treatment of such cases is often best provided by a multi-disciplinary team, where the patient’s expectations and care delivery can be optimally managed. Orthodontic treatment is often used to prepare the dentition in advance of restorative replacement of missing teeth. Conversely, the placement of implants may precede the delivery of orthodontic treatment and indeed may function as an adjunctive orthodontic procedure. We discuss the use of both approaches here and illustrate their clinical implementation with two case reports. The first case demonstrates the use of fixed appliances to prepare the mouth for an opposing implant-retained complete denture. A second case demonstrates the use of implant-retained crowns to provide orthodontic anchorage in a partially dentate patient. We propose that complex cases such as these should always be planned and treated by a multi-disciplinary team in order to optimise the delivery of care, patient experience, and treatment outcome. The presented cases add to the body of evidence in this area.Keywords: orthodontics, dental implantology, hypodontia, multi-disciplinary
Procedia PDF Downloads 1284921 Comparing Student Performance on Standardized Tests at Test Center versus through Online-Proctored Delivery
Authors: Jin Koo
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The main purpose of this study is to investigate the comparability of student scores obtained from Test Center (TC) vs. Online-Proctored (OP) Delivery in the three subject areas of Verbal, Reading, and Mathematics for each level (Middle and Upper). Also, this study examines whether there is an interaction effect between test deliveries (TC vs. OP) and gender/ethnicity/ability level in each subject area. The test used in this study is a multiple-choice standardized test for students in grades 5-11. For this study, data were collected during the 2022-23 test administration. This research used a one-factor between-subjects ANOVA and Cohen’s d to compare the TC and OP groups’ test means for each level and each subject area. Also, 2-factor between-subjects ANOVAs were conducted to investigate examinee characteristics: gender (male and female), ethnicity (African-American, Asian, Hispanic, Multi-racial, and White), and ability level (low, average, and high-ability groups). The author found that students’ test scores in some subject areas varied between TC and OP test deliveries by gender, ethnicity, and ability level, meaning that gender, ethnicity, and ability level were related to the score difference. These results will be discussed according to the current testing systems.Keywords: ability level, ethnicity, gender, online-proctored delivery, standardized test, test center
Procedia PDF Downloads 554920 Virtual Screening of Potential Inhibitors against Efflux Pumps of Mycobacterium tuberculosis
Authors: Gagan Dhawan
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Mycobacterium tuberculosis was described as ‘captain of death’ with an inherent property of multiple drug resistance majorly caused by the competent mechanism of efflux pumps. In this study, various open source tools combining chemo-informatics with bioinformatics were used for efficient in-silico drug designing. The efflux pump, Rv1218c, belonging to the ABC transporter superfamily, which is predicted to be a tetronasin-transporter in M. tuberculosis was targeted. Recent studies have shown that Rv1218c forms a complex with two more efflux pumps (Rv1219c and Rv1217c) to provide multidrug resistance to the bacterium. The 3D structure of the protein was modeled (as the structure was unavailable in the previously collected databases on this gene). The TMHMM analysis of this protein in TubercuList has shown that this protein is present in the outer membrane of the bacterium. Virtual screening of compounds from various publically available chemical libraries was performed on the M. tuberculosis protein using various open source tools. These ligands were further assessed where various physicochemical properties were evaluated and analyzed. On comparison of different physicochemical properties, toxicity and docking, the ligand 2-(hydroxymethyl)-6-[4, 5, 6-trihydroxy-2-(hydroxymethyl) tetrahydropyran-3-yl] oxy-tetrahydropyran-3, 4, 5-triol was found to be best suited for further studies.Keywords: drug resistance, efflux pump, molecular docking, virtual screening
Procedia PDF Downloads 3694919 Computational Approach to Identify Novel Chemotherapeutic Agents against Multiple Sclerosis
Authors: Syed Asif Hassan, Tabrej Khan
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Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder, of the central nervous system (CNS). In the present scenario, the current therapies either do not halt the progression of the disease or have side effects which limit the usage of current Disease Modifying Therapies (DMTs) for a longer period of time. Therefore, keeping the current treatment failure schema, we are focusing on screening novel analogues of the available DMTs that specifically bind and inhibit the Sphingosine1-phosphate receptor1 (S1PR1) thereby hindering the lymphocyte propagation toward CNS. The novel drug-like analogs molecule will decrease the frequency of relapses (recurrence of the symptoms associated with MS) with higher efficacy and lower toxicity to human system. In this study, an integrated approach involving ligand-based virtual screening protocol (Ultrafast Shape Recognition with CREDO Atom Types (USRCAT)) to identify the non-toxic drug like analogs of the approved DMTs were employed. The potency of the drug-like analog molecules to cross the Blood Brain Barrier (BBB) was estimated. Besides, molecular docking and simulation using Auto Dock Vina 1.1.2 and GOLD 3.01 were performed using the X-ray crystal structure of Mtb LprG protein to calculate the affinity and specificity of the analogs with the given LprG protein. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has a higher hypothetical affinity, also has greater negative value. Further, the non-specific ligands were screened out using the structural filter proposed by Baell and Holloway. Based on the USRCAT, Lipinski’s values, toxicity and BBB analysis, the drug-like analogs of fingolimod and BG-12 showed that RTL and CHEMBL1771640, respectively are non-toxic and permeable to BBB. The successful docking and DSX analysis showed that RTL and CHEMBL1771640 could bind to the binding pocket of S1PR1 receptor protein of human with greater affinity than as compared to their parent compound (Fingolimod). In this study, we also found that all the drug-like analogs of the standard MS drugs passed the Bell and Holloway filter.Keywords: antagonist, binding affinity, chemotherapeutics, drug-like, multiple sclerosis, S1PR1 receptor protein
Procedia PDF Downloads 2564918 E-Governance: A Key for Improved Public Service Delivery
Authors: Ayesha Akbar
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Public service delivery has witnessed a significant improvement with the integration of information communication technology (ICT). It not only improves management structure with advanced technology for surveillance of service delivery but also provides evidence for informed decisions and policy. Pakistan’s public sector organizations have not been able to produce some good results to ensure service delivery. Notwithstanding, some of the public sector organizations in Pakistan has diffused modern technology and proved their credence by providing better service delivery standards. These good indicators provide sound basis to integrate technology in public sector organizations and shift of policy towards evidence based policy making. Rescue-1122 is a public sector organization which provides emergency services and proved to be a successful model for the provision of service delivery to save human lives and to ensure human development in Pakistan. The information about the organization has been received by employing qualitative research methodology. The information is broadly based on primary and secondary sources which includes Rescue-1122 website, official reports of organizations; UNDP (United Nation Development Program), WHO (World Health Organization) and by conducting 10 in-depth interviews with the high administrative staff of organizations who work in the Lahore offices. The information received has been incorporated with the study for the better understanding of the organization and their management procedures. Rescue-1122 represents a successful model in delivering the services in an efficient way to deal with the disaster management. The management of Rescue has strategized the policies and procedures in such a way to develop a comprehensive model with the integration of technology. This model provides efficient service delivery as well as maintains the standards of the organization. The service delivery model of rescue-1122 works on two fronts; front-office interface and the back-office interface. Back-office defines the procedures of operations and assures the compliance of the staff whereas, front-office equipped with the latest technology and good infrastructure handles the emergency calls. Both ends are integrated with satellite based vehicle tracking, wireless system, fleet monitoring system and IP camera which monitors every move of the staff to provide better services and to pinpoint the distortions in the services. The standard time of reaching to the emergency spot is 7 minutes, and during entertaining the case; driver‘s behavior, traffic volume and the technical assistance being provided to the emergency case is being monitored by front-office. Then the whole information get uploaded to the main dashboard of Lahore headquarter from the provincial offices. The latest technology is being materialized by Rescue-1122 for delivering the efficient services, investigating the flaws; if found, and to develop data to make informed decision making. The other public sector organizations of Pakistan can also develop such models to integrate technology for improving service delivery and to develop evidence for informed decisions and policy making.Keywords: data, e-governance, evidence, policy
Procedia PDF Downloads 2464917 Management of Third Stage Labour in a Rural Ugandan Hospital
Authors: Brid Dinnee, Jessica Taylor, Joseph Hartland, Michael Natarajan
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Background:The third stage of labour (TSL) can be complicated by Post-Partum Haemorrhage (PPH), which can have a significant impact on maternal mortality and morbidity. In Africa, 33.9% of maternal deaths are attributable to PPH1. In order to minimise this figure, current recommendations for the developing world are that all women have active management of the third stage of labour (AMTSL). The aim of this project was to examine TSL practice in a rural Ugandan Hospital, highlight any deviation from best practice and identify barriers to change in resource limited settings as part of a 4th year medical student External Student Selected Component field trip. Method: Five key elements from the current World Health Organisation (WHO) guidelines on AMTSL were used to develop an audit tool. All daytime vaginal deliveries over a two week period in July 2016 were audited. In addition to this, a retrospective comparison of PPH rates, between 2006 (when ubiquitous use of intramuscular oxytocin for management of TSL was introduced) and 2015 was performed. Results: Eight vaginal deliveries were observed; at all of which intramuscular oxytocin was administered and controlled cord traction used. Against WHO recommendation, all umbilical cords were clamped within one minute, and no infants received early skin-to-skin contact. In only one case was uterine massage performed after placental delivery. A retrospective comparison of data rates identified a 40% reduction in total number of PPHs from November 2006 to November 2015. Maternal deaths per delivery reduced from 2% to 0.5%. Discussion: Maternal mortality and PPH are still major issues in developing countries. Maternal mortality due to PPH can be reduced by good practices regarding TSL, but not all of these are used in low-resource settings. There is a notable difference in outcomes between the developed and developing world. At Kitovu Hospital, there has been a reduction in maternal mortality and number of PPHs following introduction of IM Oxytocin administration. In order to further improve these rates, staff education and further government funding is key.Keywords: post-partum haemorrhage, PPH, third stage labour, Uganda
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