Search results for: drug safety
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5275

Search results for: drug safety

4375 Regulation, Co-Regulation and Self-Regulation of Civil Unmanned Aircrafts in Europe

Authors: M. de Miguel Molina, V. Santamarina Campos, M. V. Segarra Oña, B. de Miguel Molina

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Safety and security concerns play a key role during the design of civil UAs (aircraft controlled by a pilot who is not onboard it) by the producers and the offer of different services by the operators. At present, European countries have fragmented regulations about the manufacture and use of civil drones, therefore the European institutions are trying to approach all these regulations into a common one. In this sense, not only law but also ethics can give guidelines to the industry in order to obtain better reports from their clients. With our results, we would like to give advice to the European industry, as well as give new insights to the academia and policymakers.

Keywords: ethics, regulation, safety, security

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4374 Assessment of Nuclear Medicine Radiation Protection Practices Among Radiographers and Nurses at a Small Nuclear Medicine Department in a Tertiary Hospital

Authors: Nyathi Mpumelelo; Moeng Thabiso Maria

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BACKGROUND AND OBJECTIVES: Radiopharmaceuticals are used for diagnosis, treatment, staging and follow up of various diseases. However, there is concern that the ionizing radiation (gamma rays, α and ß particles) emitted by radiopharmaceuticals may result in exposure of radiographers and nurses with limited knowledge of the principles of radiation protection and safety, raising the risk of cancer induction. This study aimed at investigation radiation safety awareness levels among radiographers and nurses at a small tertiary hospital in South Africa. METHODS: An analytical cross-sectional study. A validated two-part questionnaire was implemented to consenting radiographers and nurses working in a Nuclear Medicine Department. Part 1 gathered demographic information (age, gender, work experience, attendance to/or passing ionizing radiation protection courses). Part 2 covered questions related to knowledge and awareness of radiation protection principles. RESULTS: Six radiographers and five nurses participated (27% males and 73% females). The mean age was 45 years (age range 20-60 years). The study revealed that neither professional development courses nor radiation protection courses are offered at the Nuclear Medicine Department understudy. However, 6/6 (100%) radiographers exhibited a high level of awareness of radiation safety principles on handling and working with radiopharmaceuticals which correlated to their years of experience. As for nurses, 4/5 (80%) showed limited knowledge and awareness of radiation protection principles irrespective of the number of years in the profession. CONCLUSION: Despite their major role of caring for patients undergoing diagnostic and therapeutic treatments, the nurses showed limited knowledge of ionizing radiation and associated side effects. This was not surprising since they never received any formal basic radiation safety course. These findings were not unique to this Centre. A study conducted in a Kuwaiti Radiology Department also established that the vast majority of nurses did not understand the risks of working with ionizing radiation. Similarly, nurses in an Australian hospital exhibited knowledge limitations. However, nursing managers did provide the necessary radiation safety training when requested. In Guatemala and Saudi Arabia, where there was shortage of professional radiographers, nurses underwent radiography training, a course that equipped them with basic radiation safety principles. The radiographers in the Centre understudy unlike others in various parts of the world demonstrated substantial knowledge and awareness on radiation protection. Radiations safety courses attended when an opportunity arose played a critical role in their awareness. The knowledge and awareness levels of these radiographers were comparable to their counterparts in Sudan. However, it was much more above that of their counterparts in Jordan, Nigeria, Nepal and Iran who were found to have limited awareness and inadequate knowledge on radiation dose. Formal radiation safety and awareness courses and workshops can play a crucial role in raising the awareness of nurses and radiographers on radiation safety for their personal benefit and that of their patients.

Keywords: radiation safety, radiation awareness, training, nuclear medicine

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4373 Identification, Isolation and Characterization of Unknown Degradation Products of Cefprozil Monohydrate by HPTLC

Authors: Vandana T. Gawande, Kailash G. Bothara, Chandani O. Satija

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The present research work was aimed to determine stability of cefprozil monohydrate (CEFZ) as per various stress degradation conditions recommended by International Conference on Harmonization (ICH) guideline Q1A (R2). Forced degradation studies were carried out for hydrolytic, oxidative, photolytic and thermal stress conditions. The drug was found susceptible for degradation under all stress conditions. Separation was carried out by using High Performance Thin Layer Chromatographic System (HPTLC). Aluminum plates pre-coated with silica gel 60F254 were used as the stationary phase. The mobile phase consisted of ethyl acetate: acetone: methanol: water: glacial acetic acid (7.5:2.5:2.5:1.5:0.5v/v). Densitometric analysis was carried out at 280 nm. The system was found to give compact spot for cefprozil monohydrate (0.45 Rf). The linear regression analysis data showed good linear relationship in the concentration range 200-5.000 ng/band for cefprozil monohydrate. Percent recovery for the drug was found to be in the range of 98.78-101.24. Method was found to be reproducible with % relative standard deviation (%RSD) for intra- and inter-day precision to be < 1.5% over the said concentration range. The method was validated for precision, accuracy, specificity and robustness. The method has been successfully applied in the analysis of drug in tablet dosage form. Three unknown degradation products formed under various stress conditions were isolated by preparative HPTLC and characterized by mass spectroscopic studies.

Keywords: cefprozil monohydrate, degradation products, HPTLC, stress study, stability indicating method

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4372 Design, Spectroscopic, Structural Characterization, and Biological Studies for New Complexes via Charge Transfer Interaction of Ciprofloxacin Drug With π Acceptors

Authors: Khaled Alshammari

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Ciprofloxacin (CIP) is a common antibiotic drug used as a strudy electron donor that interacts with dynamic π -acceptors such as 2,3-dinitrosalsylic acid (HDNS) and Tetracyanoethylene (TCNE) for synthesizing a new model of charge transfer (CT) complexes. The synthesized complexes were identified using diverse analytical methods such as UV–vis spectra, photometric titration measurements, FT-IR, HNMR Spectroscopy, and thermogravimetric analysis techniques (TGA/DTA). The stoichiometries for all the formed complexes were found to be a 1:1 M ratio between the reactants. The characteristic spectroscopic properties such as transition dipole moment (µ), oscillator strength (f), formation constant (KCT), ionization potential (ID), standard free energy (∆G), and energy of interaction (ECT) for the CT-complexes were collected. The developed CT complexes were tested for their toxicity on main organs, antimicrobial activity, antioxidant activity, and biofilm formation.

Keywords: biological, biofilm, toxicity, thermal analysis, charge transfer, spectroscopy

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4371 An Immersive Serious Game for Firefighting and Evacuation Training in Healthcare Facilities

Authors: Anass Rahouti, Guillaume Salze, Ruggiero Lovreglio, Sélim Datoussaïd

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In healthcare facilities, training the staff for firefighting and evacuation in real buildings is very challenging due to the presence of a vulnerable population in such an environment. In a standard environment, traditional approaches, such as fire drills, are often used to train the occupants and provide them with information about fire safety procedures. However, those traditional approaches may be inappropriate for a vulnerable population and can be inefficient from an educational viewpoint as it is impossible to expose the occupants to scenarios similar to a real emergency. Immersive serious games could be used as an alternative to traditional approaches to overcome their limitations. Serious games are already being used in different safety domains such as fires, earthquakes and terror attacks for several building types (e.g., office buildings, train stations, tunnels, etc.). In this study, we developed an immersive serious game to improve the fire safety skills of staff in healthcare facilities. An accurate representation of the healthcare environment was built in Unity3D by including visual and audio stimuli inspired from those employed in commercial action games. The serious game is organised in three levels. In each of them, the trainee is presented with a specific fire emergency and s/he can perform protective actions (e.g., firefighting, helping non-ambulant occupants, etc.) or s/he can ignore the opportunity for action and continue the evacuation. In this paper, we describe all the steps required to develop such a prototype, as well as the key questions that need to be answered, to develop a serious game for firefighting and evacuation in healthcare facilities.

Keywords: fire safety, healthcare, serious game, training

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4370 Reduction of the Number of Traffic Accidents by Function of Driver's Anger Detection

Authors: Masahiro Miyaji

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When a driver happens to be involved in some traffic congestion or after traffic incidents, the driver may fall in a state of anger. State of anger may encounter decisive risk resulting in severer traffic accidents. Preventive safety function using driver’s psychosomatic state with regard to anger may be one of solutions which would avoid that kind of risks. Identifying driver’s anger state is important to create countermeasures to prevent the risk of traffic accidents. As a first step, this research figured out root cause of traffic incidents by means of using Internet survey. From statistical analysis of the survey, dominant psychosomatic states immediately before traffic incidents were haste, distraction, drowsiness and anger. Then, we replicated anger state of a driver while driving, and then, replicated it by means of using driving simulator on bench test basis. Six types of facial expressions including anger were introduced as alternative characteristics. Kohonen neural network was adopted to classify anger state. Then, we created a methodology to detect anger state of a driver in high accuracy. We presented a driving support safety function. The function adapts driver’s anger state in cooperation with an autonomous driving unit to reduce the number of traffic accidents. Consequently, e evaluated reduction rate of driver’s anger in the traffic accident. To validate the estimation results, we referred the reduction rate of Advanced Safety Vehicle (ASV) as well as Intelligent Transportation Systems (ITS).

Keywords: Kohonen neural network, driver’s anger state, reduction of traffic accidents, driver’s state adaptive driving support safety

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4369 A Computational Approach to Screen Antagonist’s Molecule against Mycobacterium tuberculosis Lipoprotein LprG (Rv1411c)

Authors: Syed Asif Hassan, Tabrej Khan

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Tuberculosis (TB) caused by bacillus Mycobacterium tuberculosis (Mtb) continues to take a disturbing toll on human life and healthcare facility worldwide. The global burden of TB remains enormous. The alarming rise of multi-drug resistant strains of Mycobacterium tuberculosis calls for an increase in research efforts towards the development of new target specific therapeutics against diverse strains of M. tuberculosis. Therefore, the discovery of new molecular scaffolds targeting new drug sites should be a priority for a workable plan for fighting resistance in Mycobacterium tuberculosis (Mtb). Mtb non-acylated lipoprotein LprG (Rv1411c) has a Toll-like receptor 2 (TLR2) agonist actions that depend on its association with triacylated glycolipids binding specifically with the hydrophobic pocket of Mtb LprG lipoprotein. The detection of a glycolipid carrier function has important implications for the role of LprG in Mycobacterial physiology and virulence. Therefore, considering the pivotal role of glycolipids in mycobacterial physiology and host-pathogen interactions, designing competitive antagonist (chemotherapeutics) ligands that competitively bind to glycolipid binding domain in LprG lipoprotein, will lead to inhibition of tuberculosis infection in humans. In this study, a unified approach involving ligand-based virtual screening protocol USRCAT (Ultra Shape Recognition) software and molecular docking studies using Auto Dock Vina 1.1.2 using the X-ray crystal structure of Mtb LprG protein was implemented. 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 the higher hypothetical affinity, also has greater negative value. Based on the USRCAT, Lipinski’s values and molecular docking results, [(2R)-2,3-di(hexadecanoyl oxy)propyl][(2S,3S,5S,6R)-3,4,5-trihydroxy-2,6-bis[[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6 (hydroxymethyl)tetrahydropyran-2-yl]oxy]cyclohexyl] phosphate (XPX) was confirmed as a promising drug-like lead compound (antagonist) binding specifically to the hydrophobic domain of LprG protein with affinity greater than that of PIM2 (agonist of LprG protein) with a free binding energy of -9.98e+006 Kcal/mol and binding affinity of -132 Kcal/mol, respectively. A further, in vitro assay of this compound is required to establish its potency in inhibiting molecular evasion mechanism of MTB within the infected host macrophages. These results will certainly be helpful in future anti-TB drug discovery efforts against Multidrug-Resistance Tuberculosis (MDR-TB).

Keywords: antagonist, agonist, binding affinity, chemotherapeutics, drug-like, multi drug resistance tuberculosis (MDR-TB), RV1411c protein, toll-like receptor (TLR2)

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4368 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

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4367 Surface Modified Core–Shell Type Lipid–Polymer Hybrid Nanoparticles of Trans-Resveratrol, an Anticancer Agent, for Long Circulation and Improved Efficacy against MCF-7 Cells

Authors: M. R. Vijayakumar, K. Priyanka, Ramoji Kosuru, Lakshmi, Sanjay Singh

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Trans resveratrol (RES) is a non-flavonoid poly-phenolic compound proved for its therapeutic and preventive effect against various types of cancer. However, the practical application of RES in cancer treatment is limited because of its higher dose (up to 7.5 g/day in humans), low biological half life, rapid metabolism and faster elimination in mammals. PEGylated core-shell type lipid polymer hybrid nanoparticles are the novel drug delivery systems for long circulation and improved anti cancer effect of its therapeutic payloads. Therefore, the main objective of this study is to extend the biological half life (long circulation) and improve the therapeutic efficacy of RES through core shell type of nanoparticles. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS), a novel surfactant is applied for the preparation of PEGylated lipid polymer hybrid nanoparticles. The prepared nanoparticles were evaluated by various state of the art techniques such as dynamic light scattering (DLS) technique for particle size and zeta potential, TEM for shape, differential scanning calorimetry (DSC) for interaction analysis and XRD for crystalline changes of drug. Entrapment efficiency and invitro drug release were determined by ultracentrifugation method and dialysis bag method, respectively. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies after i.v administration were performed in sprague dawley rats. The prepared NPs were found to be spherical in shape with smooth surfaces. Particle size and zeta potential of prepared NPs were found to be in the range of 179.2±7.45 to 266.8±9.61 nm and -0.63 to -48.35 mV, respectively. DSC revealed absence of potential interaction. XRD study revealed presence of amorphous form in nanoparticles. Entrapment efficiency was found to be 83.7 % and drug release was found to be in controlled manner. MTT assay showed low MEC and pharmacokinetic studies showed higher AUC of nanoformulaition than its pristine drug. All these studies revealed that the RES loaded PEG modified core-shell type lipid polymer hybrid nanoparticles can be an alternative tool for chemopreventive and therapeutic application of RES in cancer.

Keywords: trans resveratrol, cancer nanotechnology, long circulating nanoparticles, bioavailability enhancement, core shell nanoparticles, lipid polymer hybrid nanoparticles

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4366 The Relationship between Working Models and Psychological Safety

Authors: Rosyellen Rabelo Szvarça, Pedro Fialho, Auristela Duarte de Lima Moser

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Background: New ways of working, such as teleworking or hybrid working, have changed and have impacted both employees and organizations. To understand the individuals' perceptions among different working models, this study aimed to investigate levels of psychological safety among employees working in person, hybrid, and remote environments and the correlation of demographic or professional characteristics. Methods: A cross-sectional survey was distributed electronically. A self-administered questionnaire was composed of sociodemographic data, academic status, professional contexts, working models, and the seven-item instrument of psychological safety. The psychological safety instrument was computed to determine its reliability, showing a Cronbach’s 0.75, considering a good scale when compared to the original, analyzed with 51 teams from a North American company, with a Cronbach's alpha coefficient of 0.82. Results: The survey was completed by 328 individuals, 60% of whom were in-person, 29.3% hybrid, and 10.7% remote. The Chi-Square test with the Bonferroni post-test for qualitative variables associated with the working models indicates a significant association (p 0.001) for academic qualifications. In-person models present 29.4% of individuals with secondary education and 38.1% undergraduate; hybrid present 51% postgraduate and 35.4% undergraduate. This was similar to remote workers, with 48.6% postgraduate and 34.3% undergraduate. There were no significant differences in gender composition between work models (p = 0.738), with most respondents being female in all three work groups. Remote workers predominated in areas such as commerce, marketing, and services; education and the public sector were common in the in-person group, while technology and the financial sector were predominant among hybrid workers (p < 0.001). As for leadership roles, there was no significant association with working models (p = 0.126). The decision on the working model was predominantly made by the organization for in-person and hybrid workers (p < 0.001). Preference for the working model was in line with the workers' scenario at that time (p < 0.001). Kruskal-Wallis test with Bonferroni's post hoc test compared the psychological safety scores between working groups, reveling statistically higher scores in hybrid group x̃ = 5.64 compared to in-person group x̃ = 5, with remote workers showing scores similar to other groups x̃ = 5.43 (p = 0.004). Age demonstrated no significant difference between the working groups (p = 0.052). On the other hand, organization tenure and job tenure were higher in in-person groups compared to the hybrid and remote groups (p < 0.001). The hybrid model illustrates a balance between in-person and remote models. The results highlight that higher levels of psychological safety can be correlated with the flexibility of hybrid work, as well as physical interaction, spontaneity, and informal relationships, which are considered determinants of high levels of psychological safety. Conclusions: Psychological safety at the group level using the seven-item scale is widely employed in comparison to other commonly employed measures. Despite psychological safety having been around for decades, primarily studied in in-person work contexts, the current findings contribute to expanding research with hybrid or remote settings. Ultimately, this investigation has demonstrated the significance of work models in assessing psychological safety levels.

Keywords: hybrid work, new ways of working, psychological safety, workplace, working models

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4365 Health and Safety Risk Assesment with Electromagnetic Field Exposure for Call Center Workers

Authors: Dilsad Akal

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Aim: Companies communicate with each other and with their costumers via call centers. Call centers are defined as stressful because of their uncertain working hours, inadequate relief time, performance based system and heavy workload. In literature, this sector is defined as risky as mining sector by means of health and safety. The aim of this research is to enlight the relatively dark area. Subject and Methods: The collection of data for this study completed during April-May 2015 for the two selected call centers in different parts of Turkey. The applied question mostly investigated the health conditions of call center workers. Electromagnetic field measurements were completed at the same time with applying the question poll. The ratio of employee accessibility noted as 73% for the first call center and 87% for the second. Results: The results of electromagnetic field measurements were as between 371 V/m-32 V/m for the first location and between 370 V/m-61 V/m for the second. The general complaints of the employees for both workplaces can be counted as; inadequate relief time, inadequate air conditioning, disturbance, poor thermal conditions, inadequate or extreme lighting. Furthermore, musculoskeletal discomfort, stress, ear and eye discomfort are main health problems of employees. Conclusion: The measured values and the responses to the question poll were found parallel with the other similar research results in literature. At the end of this survey, a risk map of workplace was prepared in terms of safety and health at work in general and some suggestions for resolution were provided.

Keywords: call center, health and safety, electromagnetic field, risk map

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4364 A Lower Dose of Topiramate with Enough Antiseizure Effect: A Realistic Therapeutic Range of Topiramate

Authors: Seolah Lee, Yoohyk Jang, Soyoung Lee, Kon Chu, Sang Kun Lee

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Objective: The International League Against Epilepsy (ILAE) currently suggests a topiramate serum level range of 5-20 mg/L. However, numerous institutions have observed substantial drug response at lower levels. This study aims to investigate the correlation between topiramate serum levels, drug responsiveness, and adverse events to establish a more accurate and tailored therapeutic range. Methods: We retrospectively analyzed topiramate serum samples collected between January 2017 and January 2022 at Seoul National University Hospital. Clinical data, including serum levels, antiseizure regimens, seizure frequency, and adverse events, were collected. Patient responses were categorized as "insufficient" (reduction in seizure frequency <50%) or "sufficient" (reduction ≥ 50%). Within the "sufficient" group, further subdivisions included seizure-free and tolerable seizure subgroups. A population pharmacokinetic model estimated serum levels from spot measurements. ROC curve analysis determined the optimal serum level cut-off. Results: A total of 389 epilepsy patients, with 555 samples, were reviewed, having a mean dose of 178.4±117.9 mg/day and a serum level of 3.9±2.8 mg/L. Out of the samples, only 5.6% (n=31) exhibited insufficient response, with a mean serum level of 3.6±2.5 mg/L. In contrast, 94.4% (n=524) of samples demonstrated sufficient response, with a mean serum level of 4.0±2.8 mg/L. This difference was not statistically significant (p = 0.45). Among the 78 reported adverse events, logistic regression analysis identified a significant association between ataxia and serum concentration (p = 0.04), with an optimal cut-off value of 6.5 mg/L. In the subgroup of patients receiving monotherapy, those in the tolerable seizure group exhibited a significantly higher serum level compared to the seizure-free group (4.8±2.0 mg/L vs 3.4±2.3 mg/L, p < 0.01). Notably, patients in the tolerable seizure group displayed a higher likelihood of progressing into drug-resistant epilepsy during follow-up visits compared to the seizure-free group. Significance: This study proposed an optimal therapeutic concentration for topiramate based on the patient's responsiveness to the drug and the incidence of adverse effects. We employed a population pharmacokinetic model and analyzed topiramate serum levels to recommend a serum level below 6.5 mg/L to mitigate the risk of ataxia-related side effects. Our findings also indicated that topiramate dose elevation is unnecessary for suboptimal responders, as the drug's effectiveness plateaus at minimal doses.

Keywords: topiramate, therapeutic range, low dos, antiseizure effect

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4363 The Effect of Nanocomposite on the Release of Imipenem on Bacteria Causing Infections with Implants

Authors: Mohammad Hossein Pazandeh, Monir Doudi, Sona Rostampour Yasouri

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—Results The prudent administration of antibiotics aims to avoid the side effects and the microbes' resistance to antibiotics. An approach developing methods of local administration of antibiotics is especially required for localized infections caused by bacterial colonization of medical devices or implant materials. Among the wide variety of materials used as drug delivery systems, bioactive glasses (BG) have large utilization in regenerative medicine . firstly, the production of bioactive glass/nickel oxide/tin dioxide nanocomposite using sol-gel method, and then, the controlled release of imipenem from the double metal oxide/bioactive glass nanocomposite, and finally, the investigation of the antibacterial property of the nanocomposite. against a number of implant-related infectious agents. In this study, BG/SnO2 and BG/NiO single systema with different metal oxide present and BG/NiO/SnO2 nanocomposites were synthesized by sol-gel as drug carriers for tetracycline and imepinem. These two antibiotics were widely used for osteomyelitis because of its favorable penetration and bactericidal effect on all the probable osteomyelitis pathogens. The antibacterial activity of synthesized samples were evaluated against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa as bacteria model using disk diffusion method. The BG modification using metal oxides results to antibacterial property of samples containing metal oxide with highest efficiency for nancomposite. bioactivity of all samples was assessed by determining the surface morphology, structural and composition changes using scanning electron microscopy (SEM), FTIR and X-ray diffraction (XRD) spectroscopy, respectively, after soaking in simulated body fluid (SBF) for 28 days. The hydroxyapatite formation was clearly observed as a bioactivity measurement. Then, BG nanocomposite sample was loaded using two antibiotics, separately and their release profiles were studied. The BG nancomposite sample was shown the slow and continuous drug releasing for a period of 72 hours which is desirable for a drug delivery system. The loaded antibiotic nanocomposite sample retaining antibacterial property and showing inactivation effect against bacteria under test. The modified bioactive glass forming hydroxyapatite with controlled release drug and effective against bacterial infections can be introduced as scaffolds for bone implants after clinical trials for biomedical applications . Considering the formation of biofilm by infectious bacteria after sticking on the surfaces of implants, medical devices, etc. Also, considering the complications of traditional methods, solving the problems caused by the above-mentioned microorganisms in technical and biomedical industries was one of the necessities of this research.

Keywords: antibacterial, bioglass, drug delivery system, sol- gel

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4362 Anticancer Effect of Doxorubicin Using Injectable Hydrogel

Authors: Prasamsha Panta, Da Yeon Kim, Ja Yong Jang, Min Jae Kim, Jae Ho Kim, Moon Suk Kim

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Introduction: Among the many anticancer drugs used clinically, doxorubicin (Dox), was one of widely used drugs to treat many types of solid tumors such as liver, colon, breast, or lung. Intratumoral injection of chemotherapeutic agents is a potentially more effective alternative to systemic administration because direct delivery of the anticancer drug to the target may improve both the stability and efficacy of anticancer drugs. Injectable in situ-forming gels have attracted considerable attention because they can achieve site specific drug delivery, long term action periods, and improved patient compliance. Objective: Objective of present study is to confirm clinical benefit of intratumoral chemotherapy using injectable in situ-forming poly(ethylene glycol)-b-polycaprolactone diblock copolymer (MP) and Dox with increase in efficacy and reducing the toxicity in patients with cancer diseases. Methods and methodology: We prepared biodegradable MP hydrogel and measured viscosity for the evaluation of thermo-sensitive property. In vivo antitumor activity was performed with normal saline, MP only, single free Dox, repeat free Dox, and Dox-loaded MP gel. The remaining amount of Dox drug was measured using HPLC after the mouse was sacrified. For cytotoxicity studies WST-1 assay was performed. Histological analysis was done with H&E and TUNEL processes respectively. Results: The works in this experiment showed that Dox-loaded MP have biodegradable drug depot property. Dox-loaded MP gels showed remarkable in vitro cytotoxicity activities against cancer cells. Finally, this work indicates that injection of Dox-loaded MP allowed Dox to act effectively in the tumor and induced long-lasting supression of tumor growth. Conclusion: This work has examined the potential clinical utility of intratumorally injected Dox-loaded MP gel, which shows significant effect of higher local Dox retention compared with systemically administered Dox.

Keywords: injectable in-situ forming hydrogel, anticancer, doxorubicin, intratumoral injection

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4361 Formulation of Film Forming Transdermal Spray Containing Fluconazole Using Full Factorial Design

Authors: Paresh M. Patel, Amit A. Patel, R. H. Parikh

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The present investigation was undertaken to fabricate modified transport fluconazole that belongs to BCS class II and have a poor applicability on topical infection. So to improve topical application, transdermal spray could play a vital role by using ethyl cellulose and Eudragit® S100 as film-forming polymers. Concentration of Eudragit® S100, ethyl cellulose and permeation enhancer (camphor and menthol) were selected as independent variables, whereas drying time, viscosity and in-vitro drug release were selected as dependent variables in factorial design. The viscosity, drying time and in-vitro drug release of the optimize batch B15 was 40.1 cps, 47 sec. and 90.79% respectively. The film of optimized batch was flexible and dermal-adhesive.

Keywords: Eudragit, ethyl cellulose, fluconazole, transdermal spray

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4360 The Influence of Fiber Fillers on the Bonding Safety of Wood-Adhesive Interfaces: A Fracture Energetic Approach

Authors: M. H. Brandtner-Hafner

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Adhesives have established themselves as an innovative joining technology in the wood industry. The strengths of adhesive bonding lie in the realization of lightweight designs, the avoidance of material weakening, and the joining of different types of materials. There is now a number of ways to positively influence the properties of bonded joints. One way is to add fiber fillers. This leads to an improvement in adhesion, structural integrity, and fracture toughness. In this study, the effectiveness of fiber-modified adhesives for bonding wooden joints is reviewed. A series of experimental tests were performed using the fracture analytical GF-principle to study the adhesive bonding safety and performance of the wood-adhesive interface. Two different construction adhesives based on epoxy and PUR were modified with different fiber materials and applied to bond wooden joints. The results show that bonding efficiency by adding fibrous materials to the bonding matrix leads to significant improvements in structural material properties.

Keywords: fiber-modified adhesives, bonding safety, wood-adhesive interfaces, fracture analysis

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4359 Genetically Informed Precision Drug Repurposing for Rheumatoid Arthritis

Authors: Sahar El Shair, Laura Greco, William Reay, Murray Cairns

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Background: Rheumatoid arthritis (RA) is a chronic, systematic, inflammatory, autoimmune disease that involves damages to joints and erosions to the associated bones and cartilage, resulting in reduced physical function and disability. RA is a multifactorial disorder influenced by heterogenous genetic and environmental factors. Whilst different medications have proven successful in reducing inflammation associated with RA, they often come with significant side effects and limited efficacy. To address this, the novel pharmagenic enrichment score (PES) algorithm was tested in self-reported RA patients from the UK Biobank (UKBB), which is a cohort of predominantly European ancestry, and identified individuals with a high genetic risk in clinically actionable biological pathways to identify novel opportunities for precision interventions and drug repurposing to treat RA. Methods and materials: Genetic association data for rheumatoid arthritis was derived from publicly available genome-wide association studies (GWAS) summary statistics (N=97173). The PES framework exploits competitive gene set enrichment to identify pathways that are associated with RA to explore novel treatment opportunities. This data is then integrated into WebGestalt, Drug Interaction database (DGIdb) and DrugBank databases to identify existing compounds with existing use or potential for repurposed use. The PES for each of these candidates was then profiled in individuals with RA in the UKBB (Ncases = 3,719, Ncontrols = 333,160). Results A total of 209 pathways with known drug targets after multiple testing correction were identified. Several pathways, including interferon gamma signaling and TID pathway (which relates to a chaperone that modulates interferon signaling), were significantly associated with self-reported RA in the UKBB when adjusting for age, sex, assessment centre month and location, RA polygenic risk and 10 principal components. These pathways have a major role in RA pathogenesis, including autoimmune attacks against certain citrullinated proteins, synovial inflammation, and bone loss. Encouragingly, many also relate to the mechanism of action of existing RA medications. The analyses also revealed statistically significant association between RA polygenic scores and self-reported RA with individual PES scorings, highlighting the potential utility of the PES algorithm in uncovering additional genetic insights that could aid in the identification of individuals at risk for RA and provide opportunities for more targeted interventions. Conclusions In this study, pharmacologically annotated genetic risk was explored through the PES framework to overcome inter-individual heterogeneity and enable precision drug repurposing in RA. The results showed a statistically significant association between RA polygenic scores and self-reported RA and individual PES scorings for 3,719 RA patients. Interestingly, several enriched PES pathways were targeted by already approved RA drugs. In addition, the analysis revealed genetically supported drug repurposing opportunities for future treatment of RA with a relatively safe profile.

Keywords: rheumatoid arthritis, precision medicine, drug repurposing, system biology, bioinformatics

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4358 Safety Effect of Smart Right-Turn Design at Intersections

Authors: Upal Barua

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The risk of severe crashes at high-speed right-turns at intersections is a major safety concern these days. The application of a smart right-turn at an intersection is increasing day by day to address is an issue. The design, ‘Smart Right-turn’ consists of a narrow-angle of channelization at approximately 70°. This design increases the cone of vision of the right-tuning drivers towards the crossing pedestrians as well as traffic on the cross-road. As part of the Safety Improvement Program in Austin Transportation Department, several smart right-turns were constructed at high crash intersections where high-speed right-turns were found to be a contributing factor. This paper features the state of the art techniques applied in planning, engineering, designing and construction of this smart right-turn, key factors driving the success, and lessons learned in the process. This paper also presents the significant crash reductions achieved from the application of this smart right-turn design using Empirical Bayes method. The result showed that smart right-turns can reduce overall right-turn crashes by 43% and severe right-turn crashes by 70%.

Keywords: smart right-turn, intersection, cone of vision, empirical Bayes method

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4357 Optimization of Gastro-Retentive Matrix Formulation and Its Gamma Scintigraphic Evaluation

Authors: Swapnila V. Shinde, Hemant P. Joshi, Sumit R. Dhas, Dhananjaysingh B. Rajput

Abstract:

The objective of the present study is to develop hydro-dynamically balanced system for atenolol, β-blocker as a single unit floating tablet. Atenolol shows pH dependent solubility resulting into a bioavailability of 36%. Thus, site specific oral controlled release floating drug delivery system was developed. Formulation includes novice use of rate controlling polymer such as locust bean gum (LBG) in combination of HPMC K4M and gas generating agent sodium bicarbonate. Tablet was prepared by direct compression method and evaluated for physico-mechanical properties. The statistical method was utilized to optimize the effect of independent variables, namely amount of HPMC K4M, LBG and three dependent responses such as cumulative drug release, floating lag time, floating time. Graphical and mathematical analysis of the results allowed the identification and quantification of the formulation variables influencing the selected responses. To study the gastrointestinal transit of the optimized gastro-retentive formulation, in vivo gamma scintigraphy was carried out in six healthy rabbits, after radio labeling the formulation with 99mTc. The transit profiles demonstrated that the dosage form was retained in the stomach for more than 5 hrs. The study signifies the potential of the developed system for stomach targeted delivery of atenolol with improved bioavailability.

Keywords: floating tablet, factorial design, gamma scintigraphy, antihypertensive model drug, HPMC, locust bean gum

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4356 The Preventive Effect of Metformin on Paclitaxel-Induced Peripheral Neuropathy

Authors: AliAkbar Hafezi, Jamshid Abedi, Jalal Taherian, Behnam Kadkhodaei, Mahsa Elahi

Abstract:

Background. Peripheral neuropathy is a common side effect of the administration of neurotoxic chemotherapy agents. This adverse effect is a major dose-limiting factor of many commonly used chemotherapy drugs. Currently, there are no Food and Drug Administration (FDA) approved medications for the prevention or treatment of chemotherapy-induced peripheral neuropathy. Therefore, this study was performed to investigate the efficacy and safety of metformin on paclitaxel-induced peripheral neuropathy (PIPN). Methods. In this randomized clinical trial, cancer patients who were candidates for chemotherapy with paclitaxel referred to the radiation oncology departments in Iran from 2022 to 2023 were studied. Patients were randomly divided into two groups; 1- Case group (n = 30) received metformin 500 mg orally twice a day after meals during chemotherapy with paclitaxel, and 2- Control group (30 people) received chemotherapy without metformin or any additional medication. Patients were visited in terms of numbness or other neurological symptoms two weeks before chemotherapy, 1-2 days before and weekly during chemotherapy, and at the end of the study. They were assessed by nerve conduction study (NCS) before intervention and one week after the end of chemotherapy. The primary outcome was the efficacy in reducing PIPN and the secondary outcome was adverse effects. Eventually, the outcomes were compared between the two groups of patients. Results. A total of 60 female cancer patients receiving chemotherapy with paclitaxel were evaluated in two groups. The groups were matched in terms of age, body mass index, fasting blood sugar, smoking, pathologic stage, and creatinine levels. The results showed that 18 patients (60.0 %) in the case group and 23 patients (76.6 %) in the control group had PIPN clinically (P = 0.267), and NCS showed 11 patients (36.6 %) in the case group and 15 patients (50.0 %) in the control group suffered from PIPN which no significant difference was observed between the two groups (P = 0.435). Diarrhea (n = 3; 10.0 %) and nausea (n = 3; 10.0 %) were the most common side effects of metformin in the case group and no serious side effects (lactic acidosis and anemia) were found in these patients. Conclusion. This study indicated that metformin did not significantly prevent PIPN in cancer patients receiving chemotherapy, although the frequency of peripheral neuropathy in the case group was lower than in the control group. The use of metformin in the patients had acceptable safety and no serious side effects were reported.

Keywords: peripheral neuropathy, chemotherapy, paclitaxel, metformin

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4355 A Systematic Review on Orphan Drugs Pricing, and Prices Challenges

Authors: Seyran Naghdi

Abstract:

Background: Orphan drug development is limited by very high costs attributed to the research and development and small size market. How health policymakers address this challenge to consider both supply and demand sides need to be explored for directing the policies and plans in the right way. The price is an important signal for pharmaceutical companies’ profitability and the patients’ accessibility as well. Objective: This study aims to find out the orphan drugs' price-setting patterns and approaches in health systems through a systematic review of the available evidence. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) approach was used. MedLine, Embase, and Web of Sciences were searched via appropriate search strategies. Through Medical Subject Headings (MeSH), the appropriate terms for pricing were 'cost and cost analysis', and it was 'orphan drug production', and 'orphan drug', for orphan drugs. The critical appraisal was performed by the Joanna-Briggs tool. A Cochrane data extraction form was used to obtain the data about the studies' characteristics, results, and conclusions. Results: Totally, 1,197 records were found. It included 640 hits from Embase, 327 from Web of Sciences, and 230 MedLine. After removing the duplicates, 1,056 studies remained. Of them, 924 studies were removed in the primary screening phase. Of them, 26 studies were included for data extraction. The majority of the studies (>75%) are from developed countries, among them, approximately 80% of the studies are from European countries. Approximately 85% of evidence has been produced in the recent decade. Conclusions: There is a huge variation of price-setting among countries, and this is related to the specific pharmacological market structure and the thresholds that governments want to intervene in the process of pricing. On the other hand, there is some evidence on the availability of spaces to reduce the very high costs of orphan drugs development through an early agreement between pharmacological firms and governments. Further studies need to focus on how the governments could incentivize the companies to agree on providing the drugs at lower prices.

Keywords: orphan drugs, orphan drug production, pricing, costs, cost analysis

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4354 Experimental Study of Complete Loss of Coolant Flow (CLOF) Test by System–Integrated Modular Advanced Reactor Integral Test Loop (SMART-ITL) with Passive Residual Heat Removal System (PRHRS)

Authors: Jin Hwa Yang, Hwang Bae, Sung Uk Ryu, Byong Guk Jeon, Sung Jae Yi, Hyun Sik Park

Abstract:

Experimental studies using a large-scale thermal-hydraulic integral test facility, System–integrated Modular Advanced Reactor Integral Test Loop (SMART-ITL), have been carried out to validate the performance of the prototype, SMART. After Fukushima accident, the passive safety systems have been dealt as important designs for retaining of nuclear safety. One of the concerned scenarios for evaluating the passive safety system is a Complete Loss of Coolant Flow (CLOF). The flowrate of coolant in the primary system is maintained by Reactor Coolant Pump (RCP). When the supply of electric power of RCP is shut off, the flowrate of coolant decreases sharply, and the temperature of the coolant increases rapidly. Therefore, the reactor trip signal is activated to prevent the over-heating of the core. In this situation, Passive Residual Heat Removal System (PRHRS) plays a significant role to assure the soundness of the SMART. The PRHRS using a two-phase natural circulation is a passive safety system in the SMART to eliminate the heat of steam generator in the secondary system with heat exchanger submarined in the Emergency Cooling Tank (ECT). As the RCPs continue to coast down, inherent natural circulation in the primary system transfers heat to the secondary system. The transferred heat is removed by PRHRS in the secondary system. In this paper, the progress of the CLOF accident is described with experimental data of transient condition performed by SMART-ITL. Finally, the capability of passive safety system and inherent natural circulation will be evaluated.

Keywords: CLOF, natural circulation, PRHRS, SMART-ITL

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4353 A Study to Connect the Objective Interface Design Characters To Ergonomic Safety

Authors: Gaoguang Yang, Shan Fu

Abstract:

Human-machine interface (HMI) intermediate system information to human operators to facilitate human ability to manage and control the system. Well-designed HMI would enhance human ability. An evaluation must be performed to confirm that the designed HMI would enhance but not degrade human ability. However, the prevalent HMI evaluation techniques have difficulties in more thoroughly and accurately evaluating the suitability and fitness of a given HMI for the wide variety of uncertainty contained in both the existing HMI evaluation techniques and the large number of task scenarios. The first limitation should be attributed to the subjective and qualitative analysis characteristics of these evaluation methods, and the second one should be attributed to the cost balance. This study aims to explore the connection between objective HMI characters and ergonomic safety and step forward toward solving these limitations with objective, characterized HMI parameters. A simulation experiment was performed with the time needed for human operators to recognize the HMI information as characterized HMI parameter, and the result showed a strong correlation between the parameter and ergonomic safety level.

Keywords: Human-Machine Interface (HMI), evaluation, objective, characterization, simulation

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4352 Exploring the Intricate Microbiology of Street Cuisine: Delving into Potential Dangers in Order to Enhance Safety and Quality

Authors: Raana Babadi Fathipour

Abstract:

Street foods hold a significant place in the tapestry of socioeconomic and cultural norms, beloved across the globe. Serving as a convenient and affordable option for city dwellers seeking nourishment, these culinary delights also serve as a vital source of income for vendors, particularly women. Additionally, street food acts as a mirror reflecting traditional local customs and practices, an element that draws tourists to experience the authenticity of a culture firsthand. Despite its many virtues, concerns have emerged regarding the microbiological safety of street food worldwide. Often prepared and sold in subpar conditions without proper oversight or regulation, street food has become synonymous with potential health risks. The presence of elevated levels of fecal indicator bacteria and various pathogens in these unregulated delicacies further perpetuates anxieties surrounding their consumption. This analysis delves into the intricate microbiological intricacies inherent in street food, shedding light on the pertinent safety concerns and prevalent pathogens. Additionally, it elaborates on the worldwide standing of this vital economic endeavor. Moreover, it advocates for the adoption of molecular detection techniques over conventional culture-based methods to gain a more comprehensive grasp of the true microbial risks posed by street cuisine. Acknowledgment marks the initial step towards resolving any given issue.

Keywords: foodborne pathogens, microbiological safety, street food, viruses

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4351 Design and Development of Graphene Oxide Modified by Chitosan Nanosheets Showing pH-Sensitive Surface as a Smart Drug Delivery System for Control Release of Doxorubicin

Authors: Parisa Shirzadeh

Abstract:

Drug delivery systems in which drugs are traditionally used, multi-stage and at specified intervals by patients, do not meet the needs of the world's up-to-date drug delivery. In today's world, we are dealing with a huge number of recombinant peptide and protean drugs and analogues of hormones in the body, most of which are made with genetic engineering techniques. Most of these drugs are used to treat critical diseases such as cancer. Due to the limitations of the traditional method, researchers sought to find ways to solve the problems of the traditional method to a large extent. Following these efforts, controlled drug release systems were introduced, which have many advantages. Using controlled release of the drug in the body, the concentration of the drug is kept at a certain level, and in a short time, it is done at a higher rate. Graphene is a natural material that is biodegradable, non-toxic, and natural compared to carbon nanotubes; its price is lower than carbon nanotubes and is cost-effective for industrialization. On the other hand, the presence of highly effective surfaces and wide surfaces of graphene plates makes it more effective to modify graphene than carbon nanotubes. Graphene oxide is often synthesized using concentrated oxidizers such as sulfuric acid, nitric acid, and potassium permanganate based on Hummer 1 method. In comparison with the initial graphene, the resulting graphene oxide is heavier and has carboxyl, hydroxyl, and epoxy groups. Therefore, graphene oxide is very hydrophilic and easily dissolves in water and creates a stable solution. On the other hand, because the hydroxyl, carboxyl, and epoxy groups created on the surface are highly reactive, they have the ability to work with other functional groups such as amines, esters, polymers, etc. Connect and bring new features to the surface of graphene. In fact, it can be concluded that the creation of hydroxyl groups, Carboxyl, and epoxy and in fact graphene oxidation is the first step and step in creating other functional groups on the surface of graphene. Chitosan is a natural polymer and does not cause toxicity in the body. Due to its chemical structure and having OH and NH groups, it is suitable for binding to graphene oxide and increasing its solubility in aqueous solutions. Graphene oxide (GO) has been modified by chitosan (CS) covalently, developed for control release of doxorubicin (DOX). In this study, GO is produced by the hummer method under acidic conditions. Then, it is chlorinated by oxalyl chloride to increase its reactivity against amine. After that, in the presence of chitosan, the amino reaction was performed to form amide transplantation, and the doxorubicin was connected to the carrier surface by π-π interaction in buffer phosphate. GO, GO-CS, and GO-CS-DOX characterized by FT-IR, RAMAN, TGA, and SEM. The ability to load and release is determined by UV-Visible spectroscopy. The loading result showed a high capacity of DOX absorption (99%) and pH dependence identified as a result of DOX release from GO-CS nanosheet at pH 5.3 and 7.4, which show a fast release rate in acidic conditions.

Keywords: graphene oxide, chitosan, nanosheet, controlled drug release, doxorubicin

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4350 Empowering Leadership and Constructive Voice: A Sequential Mediation Analysis

Authors: Umamaheswara Rao Jada, Susmita Mukhopadhyay

Abstract:

In the present highly complex, dynamic and interdependent organizational environment, employees' ideas, opinions and suggestions which is technically referred to as ‘constructive employee voice’ is increasingly being recognized and valued. Literature has consistently demonstrated the relevance of leadership in employee voicing behavior, however the new form of leadership, ‘empowering leadership’ has not been given much attention. The study, therefore, devotes itself to the effort to explore the impact of this new form of leadership on employee voice behavior and the interplay with leader member exchange (LMX) and psychological safety as mediators in the same. The study utilizes structural equation modeling for analyzing the data collected from 310 Indian service industry employees through the questionnaire developed for the study. The findings of the study demonstrate the significant impact of empowering form of leadership on employees’ constructive voice behavior. Additionally, supporting results were observed for the mediating impact of leader member exchange (LMX) and psychological safety between empowering leadership and employees’ constructive voice behavior. The results of this study provide insights into the intervening mechanisms by linking leaders’ empowering behavior with employees’ constructive voice, while also highlighting the potential importance of LMX relationship in organizations and psychological safety in the context of constructive voice behavior. The study brings forth the relevance of the new form of leadership, ‘empowering leadership’ for fostering the better exchange of ideas, opinions, and suggestions between leaders and followers which tend to benefit the organization, providing empirical evidence of the sequential mediation of LMX and psychological safety. The piece of work is assumed to benefit the leaders in organizations by providing them the basis for adopting empowering form of leadership in light of results displayed.

Keywords: constructive voice, empowering leadership, leader member exchange (LMX), psychological safety, sequential mediation, structural equation modeling

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4349 An Empirical Study on the Impact of Peace in Tourists' Country of Origin on Their Travel Behavior

Authors: Claudia Seabra, Elisabeth Kastenholz, José Luís Abrantes, Manuel Reis

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In a world of increasing mobility and global risks, terrorism has, in a perverse way, capitalized on contemporaneous society’s growing interest in travel to explore a world whose national boundaries and distances have decreased. Terrorists have identified the modern tourist flows originated from the economically more developed countries as new appealing targets so as to: i) call attention to the causes they defend and ii) destroy a country’s foundations of tourism, with the final aim of disrupting the economic and consequently social fabric of the affected countries. The present study analyses sensitivity towards risk and travel behaviors in international travel amongst a sample of 600 international tourists from 49 countries travelling by air. Specifically, the sample was segmented according to the Global Peace Index. This index defines country profiles regarding the levels of peace. The indicators used are established over three broad themes: i) ongoing domestic and international conflict; ii) societal safety and security; and iii) militarisation. Tourists were segmented, according to their country of origin, in different levels of peacefulness. Several facets of travel behavior were evaluated, namely motivations, attitude towards trip planning, quality perception and perceived value of the trip. Also factors related with risk perception were evaluated, specifically terrorism risk perception during the trip, unsafety sensation as well as importance attributed to safety in travel. Results contribute to our understanding of the role of previous exposure to the lack of peace and safety at home in the international tourists behaviors, which is further discussed in terms of tourism management and marketing implications which should particularly interest tourism services and destinations more affected by terrorism, war, political turmoil, crime and other safety risks.

Keywords: terrorism, tourism, safety, risk perception

Procedia PDF Downloads 441
4348 Roundabout Implementation Analyses Based on Traffic Microsimulation Model

Authors: Sanja Šurdonja, Aleksandra Deluka-Tibljaš, Mirna Klobučar, Irena Ištoka Otković

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Roundabouts are a common choice in the case of reconstruction of an intersection, whether it is to improve the capacity of the intersection or traffic safety, especially in urban conditions. The regulation for the design of roundabouts is often related to driving culture, the tradition of using this type of intersection, etc. Individual values in the regulation are usually recommended in a wide range (this is the case in Croatian regulation), and the final design of a roundabout largely depends on the designer's experience and his/her choice of design elements. Therefore, before-after analyses are a good way to monitor the performance of roundabouts and possibly improve the recommendations of the regulation. This paper presents a comprehensive before-after analysis of a roundabout on the country road network near Rijeka, Croatia. The analysis is based on a thorough collection of traffic data (operating speeds and traffic load) and design elements data, both before and after the reconstruction into a roundabout. At the chosen location, the roundabout solution aimed to improve capacity and traffic safety. Therefore, the paper analyzed the collected data to see if the roundabout achieved the expected effect. A traffic microsimulation model (VISSIM) of the roundabout was created based on the real collected data, and the influence of the increase of traffic load and different traffic structures, as well as of the selected design elements on the capacity of the roundabout, were analyzed. Also, through the analysis of operating speeds and potential conflicts by application of the Surrogate Safety Assessment Model (SSAM), the traffic safety effect of the roundabout was analyzed. The results of this research show the practical value of before-after analysis as an indicator of roundabout effectiveness at a specific location. The application of a microsimulation model provides a practical method for analyzing intersection functionality from a capacity and safety perspective in present and changed traffic and design conditions.

Keywords: before-after analysis, operating speed, capacity, design.

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4347 Ph-Triggered Cationic Solid Lipid Nanoparticles Mitigated Colitis in Mice

Authors: Muhammad Naeem, Juho Lee, Jin-Wook Yoo

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In this study, we hypothesized that prolonged gastrointestinal transit at the inflamed colon conferred by a pH-triggered mucoadhesive smart nanoparticulate drug delivery system aids in achieving selective and sustained levels of the drug within the inflamed colon for the treatment of ulcerative colitis. We developed budesonide-loaded pH-sensitive charge-reversal solid lipid nanoparticles (SLNs) using a hot homogenization method. Polyetylenimine (PEI) was used to render SLNs cationic (PEI-SLNs). Eudragit S100 (ES) was coated on PEI-SLNs for pH-trigger charge-reversal SLNs (ES-PEI-SLNs). Therapeutic potential of the prepared SNLs formulation was evaluated in ulcerative colitis in mice. The transmission electron microscopy, zeta size and zeta potential data showed the successful formation of SLNs formulations. SLNs and PEI-SLNs showed burst drug release in acidic pH condition mimicking stomach and early small intestine environment which limiting their application as oral delivery systems. However, ES-PEI-SLNs prevented a burst drug release in acidic pH conditions and showed sustained release at a colonic pH. Most importantly, the surface charge of ES-PEI-SLNs switched from negative to positive in colonic conditions by pH-triggered removal of ES coating and accumulated selectively in inflamed colon. Furthermore, a charge reversal ES-PEI-SLNs showed a superior mitigation of dextran sulfate sodium (DSS)-induced acute colitis in mice as compared to SLNs and PEI-SLNs treated groups. Moreover, histopathological analysis of distal colon sections stained with hematoxylin/eosin and E-cadherin immunostaining revealed attenuated inflammation in an ES-PEI-SLNs-treated group. We also found that ES-PEI-SLNs markedly reduced the myeloperoxidase level and expression of TNF-alpha in colon tissue. Our results suggest that the pH-triggered charge reversal SLNs presented in this study would be a promising approach for ulcerative colitis therapy.

Keywords: solid lipid nanoparticles, stimuli-triggered charge-reversal, ulcerative colitis, methacrylate copolymer, budesonide

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4346 Surface Characterization and Femtosecond-Nanosecond Transient Absorption Dynamics of Bioconjugated Gold Nanoparticles: Insight into the Warfarin Drug-Binding Site of Human Serum Albumin

Authors: Osama K. Abou-Zied, Saba A. Sulaiman

Abstract:

We studied the spectroscopy of 25-nm diameter gold nanoparticles (AuNPs), coated with human serum albumin (HSA) as a model drug carrier. The morphology and coating of the AuNPs were examined using transmission electron microscopy and dynamic light scattering. Resonance energy transfer from the sole tryptophan of HSA (Trp214) to the AuNPs was observed in which the fluorescence quenching of Trp214 is dominated by a static mechanism. Using fluorescein (FL) to probe the warfarin drug-binding site in HSA revealed the unchanged nature of the binding cavity on the surface of the AuNPs, indicating the stability of the protein structure on the metal surface. The transient absorption results of the surface plasmonic resonance (SPR) band of the AuNPs show three ultrafast dynamics that are involved in the relaxation process after excitation at 460 nm. The three decay components were assigned to the electron-electron (~ 400 fs), electron-phonon (~ 2.0 ps) and phonon-phonon (200–250 ps) interactions. These dynamics were not changed upon coating the AuNPs with HSA which indicates the chemical and physical stability of the AuNPs upon bioconjugation. Binding of FL in HSA did not have any measurable effect on the bleach recovery dynamics of the SPR band, although both FL and AuNPs were excited at 460 nm. The current study is important for a better understanding of the physical and dynamical properties of protein-coated metal nanoparticles which are expected to help in optimizing their properties for critical applications in nanomedicine.

Keywords: gold nanoparticles, human serum albumin, fluorescein, femtosecond transient absorption

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