Search results for: drug reaction with eosinophilia and systemic symptoms
6198 Monitoring Systemic Risk in the Hedge Fund Sector
Authors: Frank Hespeler, Giuseppe Loiacono
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We propose measures for systemic risk generated through intra-sectorial interdependencies in the hedge fund sector. These measures are based on variations in the average cross-effects of funds showing significant interdependency between their individual returns and the moments of the sector’s return distribution. The proposed measures display a high ability to identify periods of financial distress, are robust to modifications in the underlying econometric model and are consistent with intuitive interpretation of the results.Keywords: hedge funds, systemic risk, vector autoregressive model, risk monitoring
Procedia PDF Downloads 3256197 Pharmaceutical Science and Development in Drug Research
Authors: Adegoke Yinka Adebayo
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An understanding of the critical product attributes that impact on in vivo performance is key to the production of safe and effective medicines. Thus, a key driver for our research is the development of new basic science and technology underpinning the development of new pharmaceutical products. Research includes the structure and properties of drugs and excipients, biopharmaceutical characterisation, pharmaceutical processing and technology and formulation and analysis.Keywords: drug discovery, drug development, drug delivery
Procedia PDF Downloads 4946196 Polymer Nanocarrier for Rheumatoid Arthritis Therapy
Authors: Vijayakameswara Rao Neralla, Jueun Jeon, Jae Hyung Park
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To develop a potential nanocarrier for diagnosis and treatment of rheumatoid arthritis (RA), we prepared a hyaluronic acid (HA)-5β-cholanic acid (CA) conjugate with an acid-labile ketal linker. This conjugate could self-assemble in aqueous conditions to produce pH-responsive HA-CA nanoparticles as potential carriers of the anti-inflammatory drug methotrexate (MTX). MTX was rapidly released from nanoparticles under inflamed synovial tissue in RA. In vitro cytotoxicity data showed that pH-responsive HA-CA nanoparticles were non-toxic to RAW 264.7 cells. In vivo biodistribution results confirmed that, after their systemic administration, pH-responsive HA-CA nanoparticles selectively accumulated in the inflamed joints of collagen-induced arthritis mice. These results indicate that pH-responsive HA-CA nanoparticles represent a promising candidate as a drug carrier for RA therapy.Keywords: rheumatoid arthritis, hyaluronic acid, nanocarrier, self-assembly, MTX
Procedia PDF Downloads 2896195 Ergonomics Aspects of Work with Computers
Authors: Leena Korpinen, Rauno Pääkkönen, Fabriziomaria Gobba
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This paper is based on a large questionnaire study. The paper presents how all participants and subgroups (upper- and lower-level white-collar workers) answered the question, “Have you had an ache, pain, or numbness, which you associate with desktop computer use, in the different body parts during the last 12 months?’ 14.6% of participants (19.4% of women and 8.2% of men) reported that they had often or very often physical symptoms in the neck. Even if our results cannot prove a causal relation of symptoms with computer use, show that workers believe that computer use can influence their wellbeing: This is important when devising treatment modalities to decrease these physical symptoms.Keywords: ergonomics, work, computer, symptoms
Procedia PDF Downloads 4026194 Spatial Relationship of Drug Smuggling Based on Geographic Information System Knowledge Discovery Using Decision Tree Algorithm
Authors: S. Niamkaeo, O. Robert, O. Chaowalit
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In this investigation, we focus on discovering spatial relationship of drug smuggling along the northern border of Thailand. Thailand is no longer a drug production site, but Thailand is still one of the major drug trafficking hubs due to its topographic characteristics facilitating drug smuggling from neighboring countries. Our study areas cover three districts (Mae-jan, Mae-fahluang, and Mae-sai) in Chiangrai city and four districts (Chiangdao, Mae-eye, Chaiprakarn, and Wienghang) in Chiangmai city where drug smuggling of methamphetamine crystal and amphetamine occurs mostly. The data on drug smuggling incidents from 2011 to 2017 was collected from several national and local published news. Geo-spatial drug smuggling database was prepared. Decision tree algorithm was applied in order to discover the spatial relationship of factors related to drug smuggling, which was converted into rules using rule-based system. The factors including land use type, smuggling route, season and distance within 500 meters from check points were found that they were related to drug smuggling in terms of rules-based relationship. It was illustrated that drug smuggling was occurred mostly in forest area in winter. Drug smuggling exhibited was discovered mainly along topographic road where check points were not reachable. This spatial relationship of drug smuggling could support the Thai Office of Narcotics Control Board in surveillance drug smuggling.Keywords: decision tree, drug smuggling, Geographic Information System, GIS knowledge discovery, rule-based system
Procedia PDF Downloads 1696193 Functionalized DOX Nanocapsules by Iron Oxide Nanoparticles for Targeted Drug Delivery
Authors: Afsaneh Ghorbanzadeh, Afshin Farahbakhsh, Zakieh Bayat
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The drug capsulation was used for release and targeted delivery in determined time, place and temperature or pH. The DOX nanocapsules were used to reduce and to minimize the unwanted side effects of drug. In this paper, the encapsulation methods of doxorubicin (DOX) and the labeling it by the magnetic core of iron (Fe3O4) has been studied. The Fe3O4 was conjugated with DOX via hydrazine bond. The solution was capsuled by the sensitive polymer of heat or pH such as chitosan-g-poly (N-isopropylacrylamide-co-N,N-dimethylacrylamide), dextran-g-poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) and mPEG-G2.5 PAMAM by hydrazine bond. The drug release was very slow at temperatures lower than 380°C. There was a rapid and controlled drug release at temperatures higher than 380°C. According to experiments, the use mPEG-G2.5PAMAM is the best method of DOX nanocapsules synthesis, because in this method, the drug delivery time to certain place is lower than other methods and the percentage of released drug is higher. The synthesized magnetic carrier system has potential applications in magnetic drug-targeting delivery and magnetic resonance imaging.Keywords: drug carrier, drug release, doxorubicin, iron oxide NPs
Procedia PDF Downloads 4176192 Difficulties and Mistakes in Diagnosis During Brucellosis in Children
Authors: Taghi-Zada T. G., Hajiyeva U. K.
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Recent years, due to the development of tourism, migration and globalization, brucellosis has spread to non-endemic regions of the country in Azerbaijan and this disease has become one of the main priority areas of medicine. In our daily practice, we face patients with specific symptoms of brucellosis and also infected with this disease but misdiagnosed. It should also be noted that the symptoms and signs of brucellosis are very diverse, and since none of these signs are specific enough to confirm the diagnosis, it creates difficulties in its timely detection and diagnosis. The main purpose of the work. Therefore, the main goal of the work is to investigate the cases of delay in making the correct diagnosis in children with brucellosis and the mistakes in this matter. Material and method. 50 children with brucellosis between the ages of 6 months and 17 years were examined. The medical history and anamnesis of these children were collected, clinical-instrumental examination, and serological tests for brucellosis were performed. Patients were divided into 2 groups, taking into account the specificity of symptoms and the timely diagnosis Results. Group I included 15 (40%) children aged 3-17 years. The main specific symptoms of brucellosis in these patients; persistent or long-term fever, night sweats, arthralgia were observed. In addition to specific symptoms, anamnesis and a specific serological test confirmed the diagnosis of brucellosis. 30 (60%) patients included in group II were misdiagnosed. 3 patients (up to 1 year) were diagnosed with sepsis, 6 with acute rheumatic fever, 10 with systemic diseases, 2 with tuberculosis, 5 with Covid 19, and 4 with unspecified fever. However, we included serological tests. detailed examination revealed the presence of brucellosis in them. As can be seen, compared to group I (40%) children included in group II (60%) In modern times, brucellosis manifests itself with its own characteristics, that is, imitating a number of other diseases, which has led to wrong diagnosis. Conclusion. Thus, the lack of specificity of clinical symptoms during brucellosis in children makes diagnosis difficult, causes mistakes and non-recognition of the disease. With this in mind, physicians in predominantly endemic and even sub-endemic areas should remain vigilant about this disease and consider brucellosis in the differential diagnosis of almost every unexplained medical problem until proven otherwise.Keywords: brucellosis, pediatrics, diagnostics, serological tests
Procedia PDF Downloads 126191 Circadian-Clock Controlled Drug Transport Across Blood-Cerebrospinal Fluid Barrier
Authors: André Furtado, Rafael Mineiro, Isabel Gonçalves, Cecília Santos, Telma Quintela
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The development of therapies for central nervous system (CNS) disorders is one of the biggest challenges of current pharmacology, given the unique features of brain barriers, which limit drug delivery. Efflux transporters (ABC transporters) expressed at the blood-cerebrospinal fluid barrier (BCSFB), are the main obstacles for the delivery of therapeutic compounds into the CNS, compromising the effective treatment of brain cancer, brain metastasis from peripheral cancers, or even neurodegenerative disorders. It is thus extremely important to understand the regulation of these transporters for reducing their expression while treating a brain disorder or choosing the most appropriate conditions for drug administration. Based on the fact that the BCSFB have fine-tuned biological rhythms, studying the circadian variation of drug transport processes is critical for choosing the most appropriate time of the day for drug administration. In our study, using an in vitro model of the BCSFB, we characterized the circadian transport profile of methotrexate (MTX) and donepezil (DNPZ), two drugs involved in the treatment of cancer and Alzheimer’s Disease symptoms, respectively. We found that MTX is transported across the basal and apical membranes of the BCSFB in a circadian way. The circadian pattern of an ABC transporter, Abcc4, might be partially responsible for MTX circadian transport. Furthermore, regarding the DNPZ transport study, we observed that the regulation of Abcg2 expression by the circadian rhythm will impact the circadian-dependent transport of DNPZ across the BCSFB. Overall, our results will contribute to the current knowledge on brain pharmacoresistance at the BCSFB by disclosing how circadian rhythms control drug delivery to the brain, setting the grounds for a potential application of chronotherapy to brain diseases to enhance the efficacy of medications and minimize their side effects.Keywords: blood-cerebrospinal fluid barrier, ABC transporters, drug transport, chronotherapy
Procedia PDF Downloads 136190 Prevalence of Drug Injection among Male Prisoners in the West of Iran
Authors: Farzad Jalilian, Mehdi Mirzaei Alavijeh
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Background: Substance addiction is one of the major worldwide problems that destroys economy, familial relationships, and the abuser’s career and has several side effects; in the meantime drug injection due to the possibility of shared use of syringes among drug users could have multiple complications to be followed. The purpose of this study was to determine the prevalence of drug injection among male prisoners in Kermanshah city, the west of Iran. Methods: In this cross-sectional study 615 male prisoners were randomly selected to participate voluntarily in the study. Participants filled out a writing self-report questionnaire. Data were analyzed by the SPSS software (ver. 21.0) at 95% significant level. Results: The mean age of respondents was 31.13 years [SD: 7.76]. Mean initiation age for drug use was 14.36 years (range, 9-34 years). Almost, 39.4 % reported a history of drug use before prison. Opium (33.2%) and crystal (27.1%) was the most used drug among prisoners. Furthermore, 9.3 % had a history of injection addiction. There was a significant correlation between age, crime type, marital status, economic status, unprotected sex and drug injection (P < 0.05). Conclusion: The low age of drug abuse and the prevalence of drug injection among offenders can be as a warning for responsible; in this regard, implementation of prevention programs to risky behavior and harm reduction among high-risk groups can follow useful results.Keywords: substance abuse, drug injection, prison, Iran
Procedia PDF Downloads 4856189 Analysis of Patient No-Shows According to Health Conditions
Authors: Sangbok Lee
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There has been much effort on process improvement for outpatient clinics to provide quality and acute care to patients. One of the efforts is no-show analysis or prediction. This work analyzes patient no-shows along with patient health conditions. The health conditions refer to clinical symptoms that each patient has, out of the followings; hyperlipidemia, diabetes, metastatic solid tumor, dementia, chronic obstructive pulmonary disease, hypertension, coronary artery disease, myocardial infraction, congestive heart failure, atrial fibrillation, stroke, drug dependence abuse, schizophrenia, major depression, and pain. A dataset from a regional hospital is used to find the relationship between the number of the symptoms and no-show probabilities. Additional analysis reveals how each symptom or combination of symptoms affects no-shows. In the above analyses, cross-classification of patients by age and gender is carried out. The findings from the analysis will be used to take extra care to patients with particular health conditions. They will be forced to visit clinics by being informed about their health conditions and possible consequences more clearly. Moreover, this work will be used in the preparation of making institutional guidelines for patient reminder systems.Keywords: healthcare system, no show analysis, process improvment, statistical data analysis
Procedia PDF Downloads 2336188 Double-Spear 1-H2-1 Oncolytic-Immunotherapy for Refractory and Relapsing High-Risk Human Neuroblastoma and Glioma
Authors: Lian Zeng
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Double-Spear 1-H2-1 (DS1-H2-1) is an oncolytic virus and an innovative biological drug candidate. The chemical composition of the drug product is a live attenuated West Nile virus (WNV) containing the human T cell costimulator (CD86) gene. After intratumoral injection, the virus can rapidly self-replicate in the injected site and lyse/kill the tumor by repeated infection among tumor cells. We also established xenograft tumor models in mice to evaluate the drug candidate's efficacy on those tumors. The results from preclinical studies on transplanted tumors in immunodeficient mice showed that DS1-H2-1 had significant oncolytic effects on human-origin cancers: it completely (100%) shrieked human glioma; limited human neuroblastoma growth reached as high as 95% growth inhibition rate (%TGITW). The safety data of preclinical animal experiments confirmed that DS1-H2-1 is safe as a biological drug for clinical use. In the preclinical drug efficacy experiment, virus-drug administration with different doses did not show abnormal signs and disease symptoms in more than 300 tested mice, and no side effects or death occurred through various administration routes. Intravenous administration did not cause acute infectious disease or other side effects. However, the replication capacity of the virus in tumor tissue via intravenous administration is only 1% of that of direct intratumoral administration. The direct intratumoral administration of DS1-H2-1 had a higher rate of viral replication. Therefore, choosing direct intratumoral injection can ensure both efficacy and safety.Keywords: oncolytic virus, WNV-CD86, immunotherapy drugs, glioma, neuroblastoma
Procedia PDF Downloads 1306187 Knowledge and Perceptions of Final-year Students towards Pharmacovigilance and Adverse Drug Reaction Reporting at the Faculty of Medical Sciences, Al-Razi University - Sana`a - Yemen
Authors: Nabil A. Albaser
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Background: There is a serious problem with adverse drug reactions (ADRs) everywhere, including Yemen. Since it helps with the detection, assessment, reporting and prevention of ADRs, pharmacovigilance (PV) is an essential part of the healthcare system. The unbiased reporting of ADRs remains the foundation of PV. Students majoring in healthcare should acquire the knowledge and skills necessary to conduct PV in a range of clinical settings. The primary objective of this study was to evaluate the understanding and attitudes of final-year Pharmacy, Nursing, and Midwifery students at Al-Razi University in Sana'a, Yemen, regarding PV and ADRs reporting. Methods: The study followed descriptive cross-sectional approach. A validated, self-administered questionnaire with three parts—demographic information, knowledge, and perceptions of Pharmacovigilance was online distributed to final-year Pharmacy, Nursing, and Midwifery students. The questionnaire was given to 175 students; 122 of them responded with a percentage (69.7%). Results: The majority of respondents were male (79.5%). More than the tow-third of the students, 68.9%, were beyond the age of 23. Although the majority of students, 80%, heard about the terms of ADRs and PV, but only 50% and 57.4% of the respondents, respectively, could define the both terms correctly. However, only 11.48 % of them, nevertheless, took a PV course. More than a half of them (56.6%) had a positive perceptions towards pharmacovigilance and ADR reporting and had a moderate degree of knowledge (68.9%). Conclusion: The study demonstrated that the participants lacked sufficient knowledge of pharmacovigilance and ADR reporting. They showed a moderate level of understanding of reporting ADRs as well as a favorable opinion of dealing with and reporting ADRs. Yemen's health care curriculum should include lessons on pharmacovigilance.Keywords: adverse drug reaction reporting, pharmacovigilance, yemen, knowlegde
Procedia PDF Downloads 1186186 Modeling Optimal Lipophilicity and Drug Performance in Ligand-Receptor Interactions: A Machine Learning Approach to Drug Discovery
Authors: Jay Ananth
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The drug discovery process currently requires numerous years of clinical testing as well as money just for a single drug to earn FDA approval. For drugs that even make it this far in the process, there is a very slim chance of receiving FDA approval, resulting in detrimental hurdles to drug accessibility. To minimize these inefficiencies, numerous studies have implemented computational methods, although few computational investigations have focused on a crucial feature of drugs: lipophilicity. Lipophilicity is a physical attribute of a compound that measures its solubility in lipids and is a determinant of drug efficacy. This project leverages Artificial Intelligence to predict the impact of a drug’s lipophilicity on its performance by accounting for factors such as binding affinity and toxicity. The model predicted lipophilicity and binding affinity in the validation set with very high R² scores of 0.921 and 0.788, respectively, while also being applicable to a variety of target receptors. The results expressed a strong positive correlation between lipophilicity and both binding affinity and toxicity. The model helps in both drug development and discovery, providing every pharmaceutical company with recommended lipophilicity levels for drug candidates as well as a rapid assessment of early-stage drugs prior to any testing, eliminating significant amounts of time and resources currently restricting drug accessibility.Keywords: drug discovery, lipophilicity, ligand-receptor interactions, machine learning, drug development
Procedia PDF Downloads 1116185 Acute Asthma in Emergency Department, Prevalence of Respiratory and Non-Respiratory Symptoms
Authors: Sherif Refaat, Hassan Aref
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Background: Although asthma is a well-identified presentation to the emergency department, little is known about the frequency and percentage of respiratory and non-respiratory symptoms in patients with acute asthma in the emergency department (ED). Objective: The aim of this study is to identify the relationship between acute asthma exacerbation and different respiratory and non-respiratory symptoms including chest pain encountered by patients visiting the emergency department. Subjects and methods: Prospective study included 169 (97 females and 72 males) asthmatic patients who were admitted to emergency department of two tertiary care facility hospitals for asthma exacerbation from the period of September 2010 to August 2013, an anonyms questionnaire was used to collect symptoms and analysis of symptoms. Results: Females were 97 (57%) of the patients, mean age was 35.6 years; dyspnea on exertion was the commonest symptom accounting for 161 (95.2%) of patients, followed by dyspnea at rest 155 (91.7%), wheezing in 152 (89.9%), chest pain was present in 82 patients (48.5%), the pain was burning in 36 (43.9%) of the total patients with chest pain. Non-respiratory symptoms were seen frequently in acute asthma in ED. Conclusions: Dyspnea was the commonest chest symptoms encountered in patients with acute asthma followed by wheezing. Chest pain in acute asthma is a common symptom and should be fully studied to exclude misdiagnosis as of cardiac origin; there is a need for a better dissemination of knowledge about this disease association with chest pain. It was also noted that other non-respiratory symptoms are frequently encountered with acute asthma in emergency department.Keywords: asthma, emergency department, respiratory symptoms, non respiratory system
Procedia PDF Downloads 4256184 Pediatric Drug Resistance Tuberculosis Pattern, Side Effect Profile and Treatment Outcome: North India Experience
Authors: Sarika Gupta, Harshika Khanna, Ajay K Verma, Surya Kant
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Background: Drug-resistant tuberculosis (DR-TB) is a growing health challenge to global TB control efforts. Pediatric DR-TB is one of the neglected infectious diseases. In our previously published report, we have notified an increased prevalence of DR-TB in the pediatric population at a tertiary health care centre in North India which was estimated as 17.4%, 15.1%, 18.4%, and 20.3% in (%) in the year 2018, 2019, 2020, and 2021. Limited evidence exists about a pattern of drug resistance, side effect profile and programmatic outcomes of Paediatric DR-TB treatment. Therefore, this study was done to find out the pattern of resistance, side effect profile and treatment outcome. Methodology: This was a prospective cohort study conducted at the nodal drug-resistant tuberculosis centre of a tertiary care hospital in North India from January 2021 to December 2022. Subjects included children aged between 0-18 years of age with a diagnosis of DR-TB, on the basis of GeneXpert (rifampicin [RIF] resistance detected), line probe assay and drug sensitivity testing (DST) of M. tuberculosis (MTB) grown on a culture of body fluids. Children were classified as monoresistant TB, polyresistant TB (resistance to more than 1 first-line anti-TB drug, other than both INH and RIF), MDR-TB, pre-XDR-TB and XDR-TB, as per the WHO classification. All the patients were prescribed DR TB treatment as per the standard guidelines, either shorter oral DR-TB regimen or a longer all-oral MDR/XDR-TB regimen (age below five years needed modification). All the patients were followed up for side effects of treatment once per month. The patient outcomes were categorized as good outcomes if they had completed treatment and cured or were improving during the course of treatment, while bad outcomes included death or not improving during the course of treatment. Results: Of the 50 pediatric patients included in the study, 34 were females (66.7%) and 16 were male (31.4%). Around 33 patients (64.7%) were suffering from pulmonary TB, while 17 (33.3%) were suffering from extrapulmonary TB. The proportions of monoresistant TB, polyresistant TB, MDR-TB, pre-XDR-TB and XDR-TB were 2.0%, 0%, 50.0%, 30.0% and 18.0%, respectively. Good outcome was reported in 40 patients (80.0%). The 10 bad outcomes were 7 deaths (14%) and 3 (6.0%) children who were not improving. Adverse events (single or multiple) were reported in all the patients, most of which were mild in nature. The most common adverse events were metallic taste 16(31.4%), rash and allergic reaction 15(29.4%), nausea and vomiting 13(26.0%), arthralgia 11 (21.6%) and alopecia 11 (21.6%). Serious adverse event of QTc prolongation was reported in 4 cases (7.8%), but neither arrhythmias nor symptomatic cardiac side effects occurred. Vestibular toxicity was reported in 2(3.9%), and psychotic symptoms in 4(7.8%). Hepatotoxicity, hypothyroidism, peripheral neuropathy, gynaecomastia, and amenorrhea were reported in 2 (4.0%), 4 (7.8%), 2 (3.9%), 1(2.0%), and 2 (3.9%) respectively. None of the drugs needed to be withdrawn due to uncontrolled adverse events. Conclusion: Paediatric DR TB treatment achieved favorable outcomes in a large proportion of children. DR TB treatment regimen drugs were overall well tolerated in this cohort.Keywords: pediatric, drug-resistant, tuberculosis, adverse events, treatment
Procedia PDF Downloads 666183 Imidocloprid as a Systemic-Acquired Resistant (SAR) Inducer in Nicotiana tabacum Var. Samsun NN Infected with Tobacco Mild Green Mosaic Virus
Authors: Mohammad Reza Hossein Zadeh
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Plants have different layers of defense responses against biotic and abiotic stresses. One of the well-defined defense mechanism in plants is systemic acquired resistance (SAR) against a broad-range of pathogens. Salicylic acid (SA) plays a crucial role in regulation of the SAR pathway. It has been proved that Chemically SA-like compounds can mimic the SA signaling role. Imidocloprid is an insecticide being used to control whiteflies on crop plants. In order to study the possible role of Imidocloprid as an elicitor of SAR in plants, experiments were conducted in a completely randomized design frame with three treatments and duplicates on the detached leaves and whole Nicotiana tabacum var. Samsun NN. plants inoculated with Tobacco mild green mosaic virus (TMGMV). Compared with the effect of other SAR-inducers such as SA, Imidoclorid conferred a robust SAR induction in the infected plants. The results suggested that Imidocloprid even more powerful than SA can be considered as strong SAR inducer in the infected plants with viruses, which develop the local lesion symptoms.Keywords: imidocloprid, Nicotiana tabacum var. Samsun NN, SAR, tobacco mild green, mosaic virus
Procedia PDF Downloads 5876182 Multidrug Therapies For HIV: Hybrid On-Off, Hysteresis On-Off Control and Simple STI
Authors: Magno Enrique Mendoza Meza
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This paper deals with the comparison of three control techniques: the hysteresis on-off control (HyOOC), the hybrid on-off control (HOOC) and the simple Structured Treatment Interruptions (sSTI). These techniques are applied to the mathematical model developed by Kirschner and Webb. To compare these techniques we use a cost functional that minimize the wild-type virus population and the mutant virus population, but the main objective is to minimize the systemic cost of treatment and maximize levels of healthy CD4+ T cells. HyOOC, HOOC, and sSTI are applied to the drug therapies using a reverse transcriptase and protease inhibitors; simulations show that these controls maintain the uninfected cells in a small, bounded neighborhood of a pre-specified level. The controller HyOOC and HOOC are designed by appropriate choice of virtual equilibrium points.Keywords: virus dynamics, on-off control, hysteresis, multi-drug therapies
Procedia PDF Downloads 3946181 Proposing an Architecture for Drug Response Prediction by Integrating Multiomics Data and Utilizing Graph Transformers
Authors: Nishank Raisinghani
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Efficiently predicting drug response remains a challenge in the realm of drug discovery. To address this issue, we propose four model architectures that combine graphical representation with varying positions of multiheaded self-attention mechanisms. By leveraging two types of multi-omics data, transcriptomics and genomics, we create a comprehensive representation of target cells and enable drug response prediction in precision medicine. A majority of our architectures utilize multiple transformer models, one with a graph attention mechanism and the other with a multiheaded self-attention mechanism, to generate latent representations of both drug and omics data, respectively. Our model architectures apply an attention mechanism to both drug and multiomics data, with the goal of procuring more comprehensive latent representations. The latent representations are then concatenated and input into a fully connected network to predict the IC-50 score, a measure of cell drug response. We experiment with all four of these architectures and extract results from all of them. Our study greatly contributes to the future of drug discovery and precision medicine by looking to optimize the time and accuracy of drug response prediction.Keywords: drug discovery, transformers, graph neural networks, multiomics
Procedia PDF Downloads 1536180 Detection of Important Biological Elements in Drug-Drug Interaction Occurrence
Authors: Reza Ferdousi, Reza Safdari, Yadollah Omidi
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Drug-drug interactions (DDIs) are main cause of the adverse drug reactions and nature of the functional and molecular complexity of drugs behavior in human body make them hard to prevent and treat. With the aid of new technologies derived from mathematical and computational science the DDIs problems can be addressed with minimum cost and efforts. Market basket analysis is known as powerful method to identify co-occurrence of thing to discover patterns and frequency of the elements. In this research, we used market basket analysis to identify important bio-elements in DDIs occurrence. For this, we collected all known DDIs from DrugBank. The obtained data were analyzed by market basket analysis method. We investigated all drug-enzyme, drug-carrier, drug-transporter and drug-target associations. To determine the importance of the extracted bio-elements, extracted rules were evaluated in terms of confidence and support. Market basket analysis of the over 45,000 known DDIs reveals more than 300 important rules that can be used to identify DDIs, CYP 450 family were the most frequent shared bio-elements. We applied extracted rules over 2,000,000 unknown drug pairs that lead to discovery of more than 200,000 potential DDIs. Analysis of the underlying reason behind the DDI phenomena can help to predict and prevent DDI occurrence. Ranking of the extracted rules based on strangeness of them can be a supportive tool to predict the outcome of an unknown DDI.Keywords: drug-drug interaction, market basket analysis, rule discovery, important bio-elements
Procedia PDF Downloads 3096179 Effect of Alginate and Surfactant on Physical Properties of Oil Entrapped Alginate Bead Formulation of Curcumin
Authors: Arpa Petchsomrit, Namfa Sermkaew, Ruedeekorn Wiwattanapatapee
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Oil entrapped floating alginate beads of curcumin were developed and characterized. Cremophor EL, Cremophor RH and Tween 80 were utilized to improve the solubility of the drug. The oil-loaded floating gel beads prepared by emulsion gelation method contained sodium alginate, mineral oil and surfactant. The drug content and % encapsulation declined as the ratio of surfactant was increased. The release of curcumin from 1% alginate beads was significantly more than for the 2% alginate beads. The drug released from the beads containing 25% of tween 80 was about 70% while a higher drug release was observed with the beads containing Cremophor EL or Cremohor RH (approximately 90%). The developed floating beads of curcumin powder with surfactant provided a superior drug release than those without surfactant. Floating beads based on oil entrapment containing the drug solubilized in surfactants is a new delivery system to enhance the dissolution of poorly soluble drugs.Keywords: alginate, curcumin, floating drug delivery, oil entrapped bead
Procedia PDF Downloads 3856178 The Role of the Basel Accords in Mitigating Systemic Risk
Authors: Wassamon Kun-Amornpong
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When a financial crisis occurs, there will be a law and regulatory reform in order to manage the turmoil and prevent a future crisis. One of the most important regulatory efforts to help cope with systemic risk and a financial crisis is the third version of the Basel Accord. Basel III has introduced some measures and tools (e.g., systemic risk buffer, countercyclical buffer, capital conservation buffer and liquidity risk) in order to mitigate systemic risk. Nevertheless, the effectiveness of these measures in Basel III in adequately addressing the problem of contagious runs that can quickly spread throughout the financial system is questionable. This paper seeks to contribute to the knowledge regarding the role of the Basel Accords in mitigating systemic risk. The research question is to what extent the Basel Accords can help control systemic risk in the financial markets? The paper tackles this question by analysing the concept of systemic risk. It will then examine the weaknesses of the Basel Accords before and after the Global financial crisis in 2008. Finally, it will suggest some possible solutions in order to improve the Basel Accord. The rationale of the study is the fact that academic works on systemic risk and financial crises are largely studied from economic or financial perspective. There is comparatively little research from the legal and regulatory perspective. The finding of the paper is that there are some problems in all of the three pillars of the Basel Accords. With regards to Pillar I, the risk model is excessively complex while the benefits of its complexity are doubtful. Concerning Pillar II, the effectiveness of the risk-based supervision in preventing systemic risk still depends largely upon its design and implementation. Factors such as organizational culture of the regulator and the political context within which the risk-based supervision operates might be a barrier against the success of Pillar II. Meanwhile, Pillar III could not provide adequate market discipline as market participants do not always act in a rational way. In addition, the too-big-to-fail perception reduced the incentives of the market participants to monitor risks. There has been some development in resolution measure (e.g. TLAC and MREL) which might potentially help strengthen the incentive of the market participants to monitor risks. However, those measures have some weaknesses. The paper argues that if the weaknesses in the three pillars are resolved, it can be expected that the Basel Accord could contribute to the mitigation of systemic risk in a more significant way in the future.Keywords: Basel accords, financial regulation, risk-based supervision, systemic risk
Procedia PDF Downloads 1286177 An In-silico Pharmacophore-Based Anti-Viral Drug Development for Hepatitis C Virus
Authors: Romasa Qasim, G. M. Sayedur Rahman, Nahid Hasan, M. Shazzad Hosain
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Millions of people worldwide suffer from Hepatitis C, one of the fatal diseases. Interferon (IFN) and ribavirin are the available treatments for patients with Hepatitis C, but these treatments have their own side-effects. Our research focused on the development of an orally taken small molecule drug targeting the proteins in Hepatitis C Virus (HCV), which has lesser side effects. Our current study aims to the Pharmacophore based drug development of a specific small molecule anti-viral drug for Hepatitis C Virus (HCV). Drug designing using lab experimentation is not only costly but also it takes a lot of time to conduct such experimentation. Instead in this in silico study, we have used computer-aided techniques to propose a Pharmacophore-based anti-viral drug specific for the protein domains of the polyprotein present in the Hepatitis C Virus. This study has used homology modeling and ab initio modeling for protein 3D structure generation followed by pocket identification in the proteins. Drug-able ligands for the pockets were designed using de novo drug design method. For ligand design, pocket geometry is taken into account. Out of several generated ligands, a new Pharmacophore is proposed, specific for each of the protein domains of HCV.Keywords: pharmacophore-based drug design, anti-viral drug, in-silico drug design, Hepatitis C virus (HCV)
Procedia PDF Downloads 2716176 Reaction Rate Behavior of a Methane-Air Mixture over a Platinum Catalyst in a Single Channel Catalytic Reactor
Authors: Doo Ki Lee, Kumaresh Selvakumar, Man Young Kim
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Catalytic combustion is an environmentally friendly technique to combust fuels in gas turbines. In this paper, the behavior of surface reaction rate on catalytic combustion is studied with respect to the heterogeneous oxidation of methane-air mixture in a catalytic reactor. Plug flow reactor (PFR), the simplified single catalytic channel assists in investigating the catalytic combustion phenomenon over the Pt catalyst by promoting the desired chemical reactions. The numerical simulation with multi-step elementary surface reactions is governed by the availability of free surface sites onto the catalytic surface and thereby, the catalytic combustion characteristics are demonstrated by examining the rate of the reaction for lean fuel mixture. Further, two different surface reaction mechanisms are adopted and compared for surface reaction rates to indicate the controlling heterogeneous reaction for better fuel conversion. The performance of platinum catalyst under heterogeneous reaction is analyzed under the same temperature condition, where the catalyst with the higher kinetic rate of reaction would have a maximum catalytic activity for enhanced methane catalytic combustion.Keywords: catalytic combustion, heterogeneous reaction, plug flow reactor, surface reaction rate
Procedia PDF Downloads 2736175 Hypersensitivity Reactions Following Intravenous Administration of Contrast Medium
Authors: Joanna Cydejko, Paulina Mika
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Hypersensitivity reactions are side effects of medications that resemble an allergic reaction. Anaphylaxis is a generalized, severe allergic reaction of the body caused by exposure to a specific agent at a dose tolerated by a healthy body. The most common causes of anaphylaxis are food (about 70%), Hymenoptera venoms (22%), and medications (7%), despite detailed diagnostics in 1% of people, the cause of the anaphylactic reaction was not indicated. Contrast media are anaphylactic agents of unknown mechanism. Hypersensitivity reactions can occur with both immunological and non-immunological mechanisms. Symptoms of anaphylaxis occur within a few seconds to several minutes after exposure to the allergen. Contrast agents are chemical compounds that make it possible to visualize or improve the visibility of anatomical structures. In the diagnosis of computed tomography, the preparations currently used are derivatives of the triiodide benzene ring. Pharmacokinetic and pharmacodynamic properties, i.e., their osmolality, viscosity, low chemotoxicity and high hydrophilicity, have an impact on better tolerance of the substance by the patient's body. In MRI diagnostics, macrocyclic gadolinium contrast agents are administered during examinations. The aim of this study is to present the results of the number and severity of anaphylactic reactions that occurred in patients in all age groups undergoing diagnostic imaging with intravenous administration of contrast agents. In non-ionic iodine CT and in macrocyclic gadolinium MRI. A retrospective assessment of the number of adverse reactions after contrast administration was carried out on the basis of data from the Department of Radiology of the University Clinical Center in Gdańsk, and it was assessed whether their different physicochemical properties had an impact on the incidence of acute complications. Adverse reactions are divided according to the severity of the patient's condition and the diagnostic method used in a given patient. Complications following the administration of a contrast medium in the form of acute anaphylaxis accounted for less than 0.5% of all diagnostic procedures performed with the use of a contrast agent. In the analysis period from January to December 2022, 34,053 CT scans and 15,279 MRI examinations with the use of contrast medium were performed. The total number of acute complications was 21, of which 17 were complications of iodine-based contrast agents and 5 of gadolinium preparations. The introduction of state-of-the-art contrast formulations was an important step toward improving the safety and tolerability of contrast agents used in imaging. Currently, contrast agents administered to patients are considered to be one of the best-tolerated preparations used in medicine. However, like any drug, they can be responsible for the occurrence of adverse reactions resulting from their toxic effects. The increase in the number of imaging tests performed with the use of contrast agents has a direct impact on the number of adverse events associated with their administration. However, despite the low risk of anaphylaxis, this risk should not be marginalized. The growing threat associated with the mass performance of radiological procedures with the use of contrast agents forces the knowledge of the rules of conduct in the event of symptoms of hypersensitivity to these preparations.Keywords: anaphylactic, contrast medium, diagnostic, medical imagine
Procedia PDF Downloads 626174 Dermatomyositis: It is Not Always an Allergic Reaction
Authors: Irfan Abdulrahman Sheth, Sohil Pothiawala
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Dermatomyositis is an idiopathic inflammatory myopathy, traditionally characterized by a progressive, symmetrical proximal muscle weakness and pathognomonic or characteristic cutaneous manifestations. We report a case of a 60-year old Chinese female who was referred from polyclinic for allergic rash over the body after applying hair dye 3 weeks ago. It was associated with puffiness of face, shortness of breath and hoarse voice since last 2 weeks with decrease effort tolerance. She also complained of dysphagia/ myalgia with progressive weakness of proximal muscles and palpitations. She denied chest pain, loss of appetite, weight loss, orthopnea or fever. She had stable vital signs and appeared cushingoid. She was noted to have rash over the scalp/ face and ecchymosis over the right arm with puffiness of face and periorbital oedema. There was symmetrical muscle weakness and other neurological examination was normal. Initial impression was of allergic reaction and underlying nephrotic syndrome and Cushing’s syndrome from TCM use. Diagnostic tests showed high Creatinine kinase (CK) of 1463 u/l, CK–MB of 18.7 ug/l and Troponin –T of 0.09 ug/l. The Full blood count and renal panel was normal. EMG showed inflammatory myositis. Patient was managed by rheumatologist and discharged on oral prednisolone with methotrexate/ ergocalciferol capsule and calcium carb, vitamin D tablets and outpatient follow up. In some patients, cutaneous disease exists in the absence of objective evidence of muscle inflammation. Management of dermatomyositis begins with careful investigation for the presence of muscle disease or of additional systemic involvement, particularly of the pulmonary, cardiac or gastrointestinal systems, and for the possibility of an accompanying malignancy. Muscle disease and systemic involvement can be refractory and may require multiple sequential therapeutic interventions or, at times, combinations of therapies. Thus, we want to highlight to the physicians that the cutaneous disease of dermatomyositis should not be confused with allergic reaction. It can be particularly challenging to diagnose. Early recognition aids appropriate management of this group of patients.Keywords: dermatomyositis, myopathy, allergy, cutaneous disease
Procedia PDF Downloads 3356173 Development of pH Responsive Nanoparticles for Colon Targeted Drug Delivery System
Authors: V. Balamuralidhara
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The aim of the present work was to develop Paclitaxel loaded polyacrylamide grafted guar gum nanoparticles as pH responsive nanoparticle systems for targeting colon. The pH sensitive nanoparticles were prepared by modified ionotropic gelation technique. The prepared nanoparticles showed mean diameters in the range of 264±0.676 nm to 726±0.671nm, and a negative net charge 10.8 mV to 35.4mV. Fourier Transformed Infrared Spectroscopy (FT-IR) and Differential Scanning Calorimetry (DSC) studies suggested that there was no chemical interaction between drug and polymers. The encapsulation efficiency of the drug was found to be 40.92% to 48.14%. The suitability of the polyacrylamide grafted guar gum ERN’s for the release of Paclitaxel was studied by in vitro release at pH 1.2 and 7.4. It was observed that, there was no significant amount of drug release at gastric pH and 97.63% of drug release at pH 7.4 was obtained for optimized formulation F3 at the end of 12 hrs. In vivo drug targeting performance for the prepared optimized formulation (F3) and pure drug Paclitaxel was evaluated by HPLC. It was observed that the polyacrylamide grafted guar gum can be used to prepare nanoparticles for targeting the drug to the colon. The release performance was greatly affected by the materials used in ERN’s preparation, which allows maximum release at colon’s pH. It may be concluded that polyacrylamide grafted guar gum nanoparticles loaded with paclitaxel have desirable release responsive to specific pH. Hence it is a unique approach for colonic delivery of drug having appropriate site specificity and feasibility and controlled release of drug.Keywords: colon targeting, polyacrylamide grafted guar gum nanoparticles, paclitaxel, nanoparticles
Procedia PDF Downloads 3546172 An Analysis of the Relation between Need for Psychological Help and Psychological Symptoms
Authors: İsmail Ay
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In this study, it was aimed to determine the relations between need for psychological help and psychological symptoms. The sample of the study consists of 530 university students getting educated in University of Atatürk in 2015-2016 academic years. Need for Psychological Help Scale and Brief Symptom Inventory were used to collect data in the study. In data analysis, correlation analysis and structural equation model with latent variables were used. Normality and homogeneity analyses were used to analyze the basic conditions of parametric tests. The findings obtained from the study show that as the psychological symptoms increase, need for psychological help also increases. The findings obtained through the study were approached according to the literature.Keywords: psychological symptoms, need for psychological help, structural equation model, correlation
Procedia PDF Downloads 3686171 The Moderating Effects of Attachment Style on the Relationship between the Psychological Symptoms and Well-Being of Mental Health Practitioners in Rehabilitation Centers: A Preliminary Study
Authors: Amaba, Marinela C., Espino, Gianne Ericka S. J. Valencia, Zeia Beatriz C.
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This study aims to determine the moderating role of attachment style on the relationship between psychological symptoms and well-being of mental health practitioners in rehabilitation centers that are accredited of the Department of Health in Pampanga. Using the data gathered from 46 mental health practitioners, multiple regression models were conducted to test the main and moderating effects of attachment styles. The findings show that all three psychological symptoms namely depression, anxiety, and stress have main effects on their general well-being on a negative direction. However, attachment style did not moderate the relationship between the psychological symptoms and general well-being. On one hand, results about the relationship of psychological symptoms and well-being are consistent to previous findings of other studies while on the other hand, results in moderation were contradicting.Keywords: attachment style, psychological symptoms, well-being, mental health practitioners, rehabilitation centers
Procedia PDF Downloads 5536170 Assessment of Drug Delivery Systems from Molecular Dynamic Perspective
Authors: M. Rahimnejad, B. Vahidi, B. Ebrahimi Hoseinzadeh, F. Yazdian, P. Motamed Fath, R. Jamjah
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In this study, we developed and simulated nano-drug delivery systems efficacy in compare to free drug prescription. Computational models can be utilized to accelerate experimental steps and control the experiments high cost. Molecular dynamics simulation (MDS), in particular NAMD was utilized to better understand the anti-cancer drug interaction with cell membrane model. Paclitaxel (PTX) and dipalmitoylphosphatidylcholine (DPPC) were selected for the drug molecule and as a natural phospholipid nanocarrier, respectively. This work focused on two important interaction parameters between molecules in terms of center of mass (COM) and van der Waals interaction energy. Furthermore, we compared the simulation results of the PTX interaction with the cell membrane and the interaction of DPPC as a nanocarrier loaded by the drug with the cell membrane. The molecular dynamic analysis resulted in low energy between the nanocarrier and the cell membrane as well as significant decrease of COM amount in the nanocarrier and the cell membrane system during the interaction. Thus, the drug vehicle showed notably better interaction with the cell membrane in compared to free drug interaction with the cell membrane.Keywords: anti-cancer drug, center of mass, interaction energy, molecular dynamics simulation, nanocarrier
Procedia PDF Downloads 3416169 Structural and Functional Correlates of Reaction Time Variability in a Large Sample of Healthy Adolescents and Adolescents with ADHD Symptoms
Authors: Laura O’Halloran, Zhipeng Cao, Clare M. Kelly, Hugh Garavan, Robert Whelan
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Reaction time (RT) variability on cognitive tasks provides the index of the efficiency of executive control processes (e.g. attention and inhibitory control) and is considered to be a hallmark of clinical disorders, such as attention-deficit disorder (ADHD). Increased RT variability is associated with structural and functional brain differences in children and adults with various clinical disorders, as well as poorer task performance accuracy. Furthermore, the strength of functional connectivity across various brain networks, such as the negative relationship between the task-negative default mode network and task-positive attentional networks, has been found to reflect differences in RT variability. Although RT variability may provide an index of attentional efficiency, as well as being a useful indicator of neurological impairment, the brain substrates associated with RT variability remain relatively poorly defined, particularly in a healthy sample. Method: Firstly, we used the intra-individual coefficient of variation (ICV) as an index of RT variability from “Go” responses on the Stop Signal Task. We then examined the functional and structural neural correlates of ICV in a large sample of 14-year old healthy adolescents (n=1719). Of these, a subset had elevated symptoms of ADHD (n=80) and was compared to a matched non-symptomatic control group (n=80). The relationship between brain activity during successful and unsuccessful inhibitions and gray matter volume were compared with the ICV. A mediation analysis was conducted to examine if specific brain regions mediated the relationship between ADHD symptoms and ICV. Lastly, we looked at functional connectivity across various brain networks and quantified both positive and negative correlations during “Go” responses on the Stop Signal Task. Results: The brain data revealed that higher ICV was associated with increased structural and functional brain activation in the precentral gyrus in the whole sample and in adolescents with ADHD symptoms. Lower ICV was associated with lower activation in the anterior cingulate cortex (ACC) and medial frontal gyrus in the whole sample and in the control group. Furthermore, our results indicated that activation in the precentral gyrus (Broadman Area 4) mediated the relationship between ADHD symptoms and behavioural ICV. Conclusion: This is the first study first to investigate the functional and structural correlates of ICV collectively in a large adolescent sample. Our findings demonstrate a concurrent increase in brain structure and function within task-active prefrontal networks as a function of increased RT variability. Furthermore, structural and functional brain activation patterns in the ACC, and medial frontal gyrus plays a role-optimizing top-down control in order to maintain task performance. Our results also evidenced clear differences in brain morphometry between adolescents with symptoms of ADHD but without clinical diagnosis and typically developing controls. Our findings shed light on specific functional and structural brain regions that are implicated in ICV and yield insights into effective cognitive control in healthy individuals and in clinical groups.Keywords: ADHD, fMRI, reaction-time variability, default mode, functional connectivity
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