Search results for: drug retail outlets

Authors: Yulistiani, Muhammad Amin, Fasich

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A surface charge of the nanoparticle is a very important consideration in pulmonal drug delivery system. The zeta potential (ZP) is related to the surface charge which can predict stability of nanoparticles as nebules of liposomal amikacin. Anionic lipid such as 1,2-dipalmitoyl-sn-glycero-3-phosphatidylglycerol (DPPG) is expected to contribute to the physical stability of liposomal amikacin and the optimal ZP value. Suitable ZP can improve drug release profiles at specific sites in alveoli as well as their stability in dosage form. This study aimed to analyze the effect of DPPG on ZP values and physical stability of liposomal amikacin. Liposomes were prepared by using the reserved phase evaporation method. Liposomes consisting of DPPG, 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), cholesterol and amikacin were formulated in five different compositions 0/150/5/100, 10//150/5/100, 20/150/5/100, 30/150/5/100 and 40/150/5/100 (w/v) respectively. A chloroform/methanol mixture in the ratio of 1 : 1 (v/v) was used as solvent to dissolve lipids. These systems were adjusted in the phosphate buffer at pH 7.4. Nebules of liposomal amikacin were produced by using the vibrating nebulizer and then characterized by the X-ray diffraction, differential scanning calorimetry, particle size and zeta potential analyzer, and scanning electron microscope. Amikacin concentration from liposome leakage was determined by the immunoassay method. The study revealed that presence of DPPG could increase the ZP value. The addition of 10 mg DPPG in the composition resulted in increasing of ZP value to 3.70 mV (negatively charged). The optimum ZP value was reached at -28.780 ± 0.70 mV and particle size of nebules 461.70 ± 21.79 nm. Nebulizing process altered parameters such as particle size, conformation of lipid components and the amount of surface charges of nanoparticles which could influence the ZP value. These parameters might have profound effects on the application of nebules in the alveoli; however, negatively charge nanoparticles were unexpected to have a high ZP value in this system due to increased macrophage uptake and pulmonal clearance. Therefore, the ratio of liposome 20/150/5/100 (w/v) resulted in the most stable colloidal system and might be applicable to pulmonal drug delivery system.

Keywords: anionic lipid, dipalmitoylphosphatidylglycerol, liposomal amikacin, stability, zeta potential

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Authors: Sarah Gounden, Mukesh Dheda, Boikhutso Tlou, Elizabeth Ojewole, Frasia Oosthuizen

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Background: Antiretroviral therapy (ART) has been effective in the reduction of mortality and resulted in an improvement in the prognosis of HIV-infected patients. However, treatment with antiretrovirals (ARVs) has led to the development of many adverse drug reactions (ADRs). It is, therefore, necessary to determine the safety profile of these medicines in a South African population in order to ensure safe and optimal medicine use. Objectives: The aim of this study was to quantify ADRs experienced with the different ARVs currently used in South Africa, to determine the safety profile of ARV medicine in South Africa based on reported ADRs, and to determine the ARVs with the lowest risk profile based on specific patient populations. Methodology: This was a quantitative study. Individual case safety reports for the period January 2010 – December 2013 were obtained from the National Pharmacovigilance Center; these reports contained information on ADRs, ARV medicine, and patient demographics. Data was analysed to find associations that may exist between ADRs experienced, ARV medicines used and patient demographics. Results: A total of 1916 patient reports were received of which 1534 met the inclusion criteria for the study. The ARV with the lowest risk of ADRs were found to be lamivudine (0.51%, n=12), followed by lopinavir/ritonavir combination (0.8%, n=19) and abacavir (0.64%, n=15). A higher incidence of ADRs was observed in females compared to males. The age group 31–50 years and the weight group 61–80 kg had the highest incidence of ADRs reported. Conclusion: This study found that the safest ARVs to be used in a South African population are lamivudine, abacavir, and the lopinavir/ritonavir combination. Gender differences play a significant role in the occurrence of ADRs and both anatomical and physiological differences account for this. An increased BMI (body mass index) in both men and women showed an increase in the incidence of ADRs associated with ARV therapy.

Keywords: adverse drug reaction, antiretrovirals, HIV/AIDS, pharmacovigilance, South Africa

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Authors: T. Hojageldiyev, Y. Bolmammedov, S. Gurbanaliyev

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It is known that drugs used in the treatment of tuberculosis show toxic effect to organism especially to liver besides its therapeutic effect. Because of ineffectiveness of drugs used in the treatment regimen of tuberculosis against multidrug resistance (MDR) and extensively drug-resistance (XDR) tuberculosis requires the development of new treatment methods and new, novel drugs. Considering the usage of Artemisia absinthium in traditional medicine in treatment of wounds which suggests its antibacterial activity it seems that, also it may have significant antimycobacterial activity. The objective of present study was to evaluate antibacterial activity of ethanolic extract of A. absinthium against M. tuberculosis. In this study, the effect of ethanolic extract of A. absinthium was tested against tuberculosis and pharmaco-toxicological properties evaluated on laboratory animals. The 20%, 40%, 70% and 96% ethanolic extracts of A. absinthium prepared then its bacteriostatic and bactericidal activities were evaluated by validated methods. Data were analyzed by GraphPad Prism 7.0 at the level P < 0.05. Results showed that ethanolic extracts of A. absinthium show no toxicological properties with having high LD50. All concentrations of extract show high bacteriostatic activity on M. tuberculosis. 96% ethanolic extract has highest bactericidal effect among other concentrations. By conducting further studies, as a result of our study, antimycobacterial drug can be prepared from A. absinthium.

Keywords: Artemisia absinthium, antimycobacterial, ethanolic extract, Mycobacteria tuberculosis

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Authors: Elena G. Salina, Vadim A. Makarov

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With the emergence of primary resistance to the current drugs and wide distribution of latent tuberculosis infection, a need for new compounds with a novel mode of action is growing steadily. Copper-mediated innate immunity and antibacterial toxicity propose novel strategies in TB drug discovery and development. Transcriptome of M. tuberculosis was obtained by RNA-seq, intracellular copper content was measured by ISP MS and complexes of 1-hydroxy-2-thiopyridines with copper were detected by HPLC.1-hydroxy-2-thiopyridine derivatives were found to be highly active in vitro against both actively growing and dormant non-culturable M. tuberculosis. Transcriptome response to 1-hydroxy-2-thiopyridines revealed signs of copper toxicity in M. tuberculosis bacilli. Indeed, Cu was found to accumulate inside cells treated with 1-hydroxy-2-thiopyridines. These compounds were found to form stable charged lipophylic complexes with Cu²⁺ ions which transport into mycobacterial cell. Subsequent metabolic destruction of the complex led to transformation of 1-hydroxy-2-thiopyridines into 2-methylmercapto-2-ethoxycarbonylpyridines, which did not possess antitubercular activity and releasing of free Cu²⁺ in the cytoplasm. 1-hydroxy-2-thiopyridines are a potent class of Cu-dependent inhibitors of M. tuberculosis which may control M. tuberculosis infection by impairment of copper homeostasis. Acknowledgment: This work was financially supported by the Ministry of Education and Science of the RussianFederation (Agreement No 14.616.21.0065; unique identifier RFMEFI61616X0065).

Keywords: copper toxicity, drug discovery, M. tuberculosis inhibitors, 2-thiopyridines

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Authors: Rachel Fanelwa Ajayi, Anovuyo Jonnas, Emmanuel I. Iwuoha

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Tuberculosis (TB) is an infectious disease caused by the bacterium (Mycobacterium tuberculosis) which has a predilection for lung tissue due to its rich oxygen supply. The mycobacterial cell has a unique innate characteristic which allows it to resist human immune systems and drug treatments; hence, it is one of the most difficult of all bacterial infections to treat, let alone to cure. At the same time, multi-drug resistance TB (MDR-TB) caused by poorly managed TB treatment, is a growing problem and requires the administration of expensive and less effective second line drugs which take much longer treatment duration than fist line drugs. Therefore, to acknowledge the issues of patients falling ill as a result of inappropriate dosing of treatment and inadequate treatment administration, a device with a fast response time coupled with enhanced performance and increased sensitivity is essential. This study involved the synthesis of electroactive platforms for application in the development of nano-biosensors suitable for the appropriate dosing of clinically diagnosed patients by promptly quantifying the levels of the TB drug; Isonaizid. These nano-biosensors systems were developed on gold surfaces using the enzyme N-acetyletransferase 2 coupled to the cysteamine modified poly(8-anilino-1-napthalene sulphonic acid)/zinc oxide nanocomposites. The morphology of ZnO nanoparticles, PANSA/ZnO nano-composite and nano-biosensors platforms were characterized using High-Resolution Transmission Electron Microscopy (HRTEM) and High-Resolution Scanning Electron Microscopy (HRSEM). On the other hand, the elemental composition of the developed nanocomposites and nano-biosensors were studied using Fourier Transform Infra-Red Spectroscopy (FTIR) and Energy Dispersive X-Ray (EDX). The electrochemical studies showed an increase in electron conductivity for the PANSA/ZnO nanocomposite which was an indication that it was suitable as a platform towards biosensor development.

Keywords: N-acetyletransferase 2, isonaizid, tuberculosis, zinc oxide

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Authors: Iddrisu Ibrahim, Joseph Atia Ayariga, Junhuan Xu, Daniel A. Abugri, Robertson K. Boakai, Olufemi S. Ajayi

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The recalcitrance of pathogenic bacteria indicates that millions of people who are at risk of infection arising from chronic diseases, surgery, organ transplant, diabetes, and several other debilitating diseases present an aura of potentially untreatable illness due to resistance development. Antimicrobial resistance has successfully become a global health menace, and resistances are often acquired by bacteria through health-care-related incidence (HRI) orchestrated by multi-drug resistant (MDR) and extended drug-resistant pathogens (EDRP). To understand the mechanisms S. Typhimurium uses to resist CDB, we study the abundance of LPS modification, Ergosterols, Mysristic palmitic resistance, Oleic acid resistance of susceptible and resistant S. Typhimurium. Using qPCR, we also analyzed the expression of selected genes known for enabling resistance in S. Typhimurium. We found high abundance of LPS, Ergosterols, Mysristic palmitic resistance, Oleic acid resistance of and high expression of resistant genes in S. Typhimurium compared to the susceptible strain. LPS modification, Ergosterols, Mysristic palmitic resistance, Oleic acid and genes such as Fims, integrons, blaTEM are important indicators of resistance development of S. typhimurium.

Keywords: antimicrobials, resistance, Cannabidiol, Salmonella, blaTEM, fimA, Lipopolysaccharide, Ergosterols

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Authors: Melissa Langevin, Natalie Ward, Colleen Fitzgibbons, Christa Ramsey, Melanie Hogue, Anna Theresa Lobos

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Description: Root Cause Analysis (RCA) is used by health care teams to examine adverse events (AEs) to identify causes which then leads to recommendations for prevention Despite widespread use, RCA has limitations. Best practices have not been established for implementing recommendations or tracking the impact of interventions after AEs. During phase 1 of this study, we used simulation to analyze two fictionalized AEs that occurred in hospitalized paediatric patients to identify and understand how the errors occurred and generated recommendations to mitigate and prevent recurrences. Scenario A involved an error of commission (inpatient drug error), and Scenario B involved detecting an error that already occurred (critical care drug infusion error). Recommendations generated were: improved drug labeling, specialized drug kids, alert signs and clinical checklists. Aim: Use simulation to optimize interventions recommended post critical event analysis prior to implementation in the clinical environment. Methods: Suggested interventions from Phase 1 were designed and tested through scenario simulation in the clinical environment (medicine ward or pediatric intensive care unit). Each scenario was simulated 8 times. Recommendations were tested using different, voluntary teams and each scenario was debriefed to understand why the error was repeated despite interventions and how interventions could be improved. Interventions were modified with subsequent simulations until recommendations were felt to have an optimal effect and data saturation was achieved. Along with concrete suggestions for design and process change, qualitative data pertaining to employee communication and hospital standard work was collected and analyzed. Results: Each scenario had a total of three interventions to test. In, scenario 1, the error was reproduced in the initial two iterations and mitigated following key intervention changes. In scenario 2, the error was identified immediately in all cases where the intervention checklist was utilized properly. Independently of intervention changes and improvements, the simulation was beneficial to identify which of these should be prioritized for implementation and highlighted that even the potential solutions most frequently suggested by participants did not always translate into error prevention in the clinical environment. Conclusion: We conclude that interventions that help to change process (epinephrine kit or mandatory checklist) were more successful at preventing errors than passive interventions (signage, change in memory aids). Given that even the most successful interventions needed modifications and subsequent re-testing, simulation is key to optimizing suggested changes. Simulation is a safe, practice changing modality for institutions to use prior to implementing recommendations from RCA following AE reviews.

Keywords: adverse events, patient safety, pediatrics, root cause analysis, simulation

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Authors: Faisal O. Al-Otaibi, Arthur T. Tucker, Richard M. Langford, Stuart Ratcliffe, Atholl Johnston, Terry D. Lee, Kenneth B. Kirby, Chandan A. Alam

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The Transdermal Delivery System (TDS®) is a proprietary liquid formulation that can be applied to intact skin via a metered pump spray to facilitate drug delivery to the circulation. The aim of this study was to assess the ability of the TDS preparation to deliver diazepam systemically, and to characterize the pharmacokinetic profile of the drug in healthy adult subjects. We conducted a randomized, single-dose, two-period, crossover phase I (pharmacokinetic) comparative study in twelve healthy volunteers. All volunteers received both 10 mg TDS-diazepam topically to the upper chest and 10 mg of the rectal diazepam preparation (Diastat®, 10 mg diazepam gel), with a minimum washout of 14 days between dosing episodes. Both formulations were well tolerated in all volunteers. Following topical application of TDS-diazepam, the mean AUC0-72h was 1241 ng/mL.h and the Cmax 34 ng/mL. The values for rectal Diastat were 4109 ng/mL.h and 300 ng/mL respectively. This proof of concept study demonstrates that the TDS preparation successfully delivered diazepam systemically to adults. As expected, the concentration of diazepam following the TDS application was lower and not bioequivalent to rectal gel. Future development of this unique system is required.

Keywords: transdermal delivery system, diazepam, seizure, bioequivalence, pharmacokinetic

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Authors: Jasmin H. Kwon , Thomas M. Brinthaupt

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There is a general lack of consumer behavior research on seasonal shopping events. Studying these kinds of events is interesting and important for several reasons. First, global shopping opportunities have implications for cross-cultural shopping events and effects on seasonal events in other countries. Second, seasonal shopping events are subject to economic conditions and may wane in popularity, especially with e-commerce options. Third, retailers can expand the success of their seasonal shopping events by taking advantage of cross-cultural opportunities. Fourth, it is interesting to consider how consumers from other countries might take advantage of different countries’ seasonal shopping events. Many countries have seasonal shopping events such as Black Friday. Research on these kinds of events can lead to the identification of cross-cultural similarities and differences in consumer behavior. We compared shopping motivations of college students who did (n=36) and did not (n=81) shop on Cyber Monday. The results showed that the groups did not differ significantly on any of the shopping motivation subscales. The Cyber Monday shoppers reported being significantly more likely to agree than disagree that their online shopping experience was enjoyable and exciting. They were more likely to disagree than agree that their experience was overwhelming. In addition, they agreed that they shopped only for deals, purchased the exact items they wanted, and thought that their efforts were worth it. Finally, they intended to shop again at next year’s Cyber Monday. It appears that there are many positive aspects to online seasonal shopping, independent of one’s typical shopping motivations. Different countries have seasonal events similar to the Black Friday and Cyber Monday shopping holiday (e.g., Boxing Day, Fukubukuro, China’s Singles Day). In Korea, there is increasing interest in taking advantage of U.S. Black Friday and Cyber Monday opportunities. Government officials are interested in adapting the U.S. holiday to Korean retailers, essentially recreating the Black Friday/Cyber Monday holiday there. Similarly, the Japanese Fukubukuro ('Lucky Bag') holiday is being adapted by other countries such as Korea and the U.S. International shipping support companies are also emerging that help customers to identify and receive products from other countries. U.S. department stores also provide free shipping on international orders for certain items. As these structural changes are occurring and new options for global shopping emerge, the need to understand the role of shoppers’ motivations becomes even more important. For example, the Cyber Monday results are particularly relevant to the new landscape with e-commerce and cross-cultural opportunities, since many of these events involve e-commerce. Within today’s global market, physical location of a retail store is no longer a limitation to growing one’s market share. From a consumer perspective, it is important to investigate how shopping motivations are related to e-commerce seasonal events. From a retail perspective, understanding the shopping motivations of international customers would help retailers to expand and better tailor their seasonal shopping events beyond the boundaries of their own countries. From a collaborative perspective, research on this topic can include interdisciplinary researchers, including those from fashion merchandising, marketing, retailing, and psychology.

Keywords: Black Friday, cross-cultural research, Cyber Monday, seasonal shopping behavior

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Authors: Donna L. Roberts

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Heroin has appeared on the drug scene before. Yet the current opioid crisis differs in significant ways. In order to address the grave challenges, this epidemic poses, the unique precipitating and sustaining conditions must be thoroughly examined. This research explored the various aspects of the political, economic, and social conditions that created a 'perfect storm' for the evolution and maintenance of the current opioid crisis. Specifically, the epidemiology, demographics, and progression of addiction inherent in the current crisis were compared to the patterns of past opioid use. Additionally, the role of pharmaceutical companies and prescribing physicians, the nature and pharmaceutical properties of the available substances and the changing socioeconomic climate were considered. Results indicated that the current crisis differs significantly with respect to its evolution, magnitude, prevalence, and widespread societal effects. Precipitated by a proliferation of prescription medication and sustained by the availability of cheaper, more potent street drugs, including new versions of synthetic opioids, the current crisis presents unprecedented challenges affecting a wider and more diverse segment of society. The unique aspects of this epidemic demand unique approaches to addressing the problem. Understanding these differences is a key step in working toward a practical and enduring solution.

Keywords: addiction, drug abuse, opioids, opioid crisis

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Authors: Kye Gilder, Kevin Shan, Amy Halseth, Steve Smith

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This study assessed the effect of prolonged-release naltrexone 32 mg/bupropion 360 mg (NB) on cardiovascular (CV) events in overweight/obese participants at elevated CV risk. Participants must lose ≥2% body weight at 16 wks, without a sustained increase in blood pressure, to continue drug. Only serious adverse events (SAE) and adverse events leading to discontinuation of study drug (AELDSD) were collected. The study was terminated early after second interim analysis with 50% of all CV events. Data on CV endpoints has been published. Current analyses focused on AEs in participants on antidepressants at baseline, as these individuals were excluded from Phase 3 trials. Intent-to-treat (ITT) population (placebo [PBO] N=4450, NB N=4455) was 54.5% female, 83.5% white, mean age of 61 yrs, mean BMI 37.3 kg/m2, 22.8% with a history of depression, 23.1% on antidepressants, including 15.4% on an SSRI. SAEs in participants receiving antidepressants was similar between NB (10.7%) and PBO (9.9%) and also similar to overall population (9.5% NB, 8.1% PBO). SAEs in those on SSRIs were similar, 10.1% NB and PBO 9.4%. For those on SSRIs or other antidepressants, AELDSDs were similar to overall population and were primarily GI disorders. Obesity increases the risk of developing depression. For participants taking NB and antidepressants, including SSRIs, there is a similar AE profile as the overall population and data revealed no evidence of an additional health risk with combined use.

Keywords: antidepressant, Contrave, Mysimba, obesity, pharmacotherapy

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Authors: Indu Lata Kanwar, Preeti K. Suresh

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The aim of this study is to fabricate hydroxyapatite based nanocomposites for local drug delivery in periodontal pockets. Hydroxyapatite is chemically similar to the mineral component of bones and hard tissues in mammals. Synthetic biocompatibility and bioactivity with human teeth and bone, making it very attractive for biomedical applications. Nanocomposite is a multiphase solid material where one of the phases has one, two or three dimensions of less than 100 nanometres (nm), or structures having nano­scale repeat distances between the different phases that make up the material. Nanostructured calcium phosphate materials play an important role in the formation of hard tissues in nature. It is reported that calcium phosphates materials in nano-size can mimic the dimensions of constituent components of calcified tissues. Nano-sized materials offer improved performances compared with conventional materials due to their large surface-to-volume ratios. The specific biological properties of the nanocomposites, as well as their interaction with cells, include the use of bioactive molecules. The approach of periodontal tissue engineering is considered promising to restore bone defect through the use of engineered materials with the aim that they will prohibit the invasion of fibrous connective tissue and help repair the function during bone regeneration.

Keywords: bioactive, hydroxyapatite, nanocomposities, periondontal

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Authors: Hafsah Javed

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Environment protection is a major issue grabbing widespread attention of policymakers, both, locally and globally. Pakistan is among the countries most affected by global climate changes; media, besides governments, have a prime responsibility to create awareness among people about its hazards, and managing strategies. Advances in Information Communication Technologies have eased people's access to information and created an interactive space to discuss environment related issues and influence the policy decisions on the issue. This study, therefore, aims to examine, from the perspective of the audience, the contribution of Pakistani traditional and social media in creating awareness about Environment Protection and its implications. The objectives are achieved through quantitative survey method. Young university students are selected as ‘audience’ for the study. The findings show lack of awareness among people regarding environment protection. Neither traditional media outlets like radio, TV and newspapers prioritize the issue on their agenda, nor audience pull information about the issue from social media. A stark indifference and non-serious attitude is being exercised towards the issue from two quarters. People do not know much about local and international laws on environment; media are used more than a source of entertainment than awareness. The study implicates that there is an exigency to launch a nationwide awareness campaign on the issue, and for that media need to be on the driving seat.

Keywords: awareness, climate change, environment protection, new media, role of media, youngsters

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Authors: Robert O'Mochain

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Over seven years have passed since the #MeToo movement first became prominent in Japan. Opinions vary on the degree of success of the movement along with its offshoot campaigns. This chapter suggests that a range of historical factors help to account for the relative lack of success of #MeToo in Japan, but that the gains achieved should also be highlighted. Our interviews with a range of activists provide insights into the nature of #MeToo in Japan and how it should be contextualized in the contemporary landscape of feminist movements here. In spite of the gains that have been made, it remains clear that levels of abuse and of non-reporting remain worryingly high and calls for well-resourced campaigns for ‘Awareness, Prevention, and Response’ are as timely as ever. Surprisingly, a case of sexual abuse involving boys and young men who were the victims of the sexual predator and entertainment mogul, Johnny Kitagawa, may be the clearest sign of change in Japanese society regarding victims of sexual abuse. In the post-#MeToo era, it was possible for these victims to come forward and attain some measure of justice. It was also possible for members of the public to strongly condemn the failures of the mass media journalists who ignored the evidence of sexual abuse for many years. Nevertheless, the case itself does not constitute reliable evidence that conditions have changed significantly for all victims of abuse or that media outlets will live up to their promises about reporting abuse.

Keywords: #MeToo, significance, Japan, prevention, response

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Authors: Anupam Purwar

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In conventional consumer product industry, stockouts are taken care by carrying buffer stock to check underserving caused by changes in customer demand, incorrect forecast or variability in lead times. But, for food outlets, the alternate of carrying buffer stock is unviable because of indispensable need to serve freshly cooked meals. Besides, the food outlet being the sole provider has no incentives to reduce stockouts, as they have no fear of losing revenue, gross profit, customers and market share. Hence, innovative, easy to implement and practical ways of addressing the twin problem of long queues and poor customer experience needs to be investigated. Current work analyses the demand pattern of 11 different food items across a routine day. Based on this optimum resource allocation for all food items has been carried out by solving a linear programming problem with cost minimization as the objective. Concurrently, recommendations have been devised to address this demand and supply side problem keeping in mind their practicability. Currently, the recommendations are being discussed and implemented at ISB (Indian School of Business) Hyderabad campus.

Keywords: F&B industry, resource allocation, demand management, linear programming, LP, queuing analysis

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Authors: Ivana Lolic, Petar Soric, Mirjana Cizmesija

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Based on Business and Consumer Survey (BCS) data, the European Commission (EC) regularly publishes the monthly Economic Sentiment Indicator (ESI) for each EU member state. ESI is conceptualized as a leading indicator, aimed ad tracking the overall economic activity. In calculating ESI, the EC employs arbitrarily chosen weights on 15 BCS response balances. This paper raises the predictive quality of ESI by applying nonlinear programming to find such weights that maximize the correlation coefficient of ESI and year-on-year GDP growth. The obtained results show that the highest weights are assigned to the response balances of industrial sector questions, followed by questions from the retail trade sector. This comes as no surprise since the existing literature shows that the industrial production is a plausible proxy for the overall Croatian economic activity and since Croatian GDP is largely influenced by the aggregate personal consumption.

Keywords: business and consumer survey, economic sentiment indicator, leading indicator, nonlinear optimization with constraints

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Authors: Yingjeng James Li, Chiao-Chih Hu

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Membrane electrode assemblies (MEAs) for proton exchange membrane fuel cell (PEMFC) applications were prepared by using 10 and 15 um PEMs. Except for different membrane thicknesses, these MEAs were prepared by the same conditions. They were prepared by using catalyst coated membrane (CCM) process. The catalyst employed is 40% Pt/C, and the Pt loading is 0.5mg/cm² for the sum of anode and cathode. Active area of the MEAs employed in this study is 5cm*5cm=25cm². In polarization measurements, the flow rates were always set at 1.2 stoic for anode and 3.0 stoic for cathode. The outlets were in open-end mode. The flow filed is tri-serpentine design. The cell temperatures and the humidification conditions were varied for the purpose of MEA performance observations. It was found that the performance of these two types of MEAs is about the same at fully or partially humidified operation conditions; however, 10um MEA exhibits higher current density in dry or low humidified conditions. For example, at 70C cell, 100% RH, and 0.6V condition, both MEAs have similar current density which is 1320 and 1342mA/cm² for 15um and 10um product, respectively. However, when in operation without external humidification, 10um MEA can produce 1085mA/cm²; whereas 15um MEA produces only 720mA/cm².

Keywords: fuel cell, membrane electrode assembly, PEFC, PEMFC, proton exchange membrane

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Authors: S. J. Sirima, C. Thirawan, R.Puntharikorn, K. Ungsumalin, J. Kaemwich

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Acinetobacter spp. is a gram negative bacterium causing the high incidence of multi-drug resistance in patients admitted to an intensive care unit. A hundred isolates of Imipenem-resistant Acinetobacter spp. isolated from patients admitted at tertiary health care center, Northeastern region, Ubon Ratchathani, Thailand, were subjected to modified Hodge test and combined disc test in order to evaluate the production of carbapenemases. The results revealed that about 35% of isolates were found to be carbapenemases producers. In addition, multiplex polymerase chain reactions were performed to detect blaOXA-like genes. It showed that 92% of isolates possess blaOXA-51-like and blaOXA-23-like genes. However, blaOXA-58-like gene was detected in only 8 isolates. No detection of blaOXA-24-like gene was observed in all isolates. In conclusion, an ability to produce carbepenemases would be an important mechanism of multi-drug resistance among clinical isolates of Acinetobacter spp. at tertiary health care center, Northeastern region, Ubon Ratchathani, Thailand. Furthermore, it was likely that the class D carbapenemases genes, blaOXA-51-like and blaOXA-23-like, might contribute to imipenem-resistance exhibiting among isolates.

Keywords: Acinetobacter spp., blaOXA-like genes, carbapenemases, tertiary health care center

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Authors: T. Mahesh, M. K. Samanta

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Antibody dug conjugate (ADC’s) concept is a less explored and more trustable for the treatment of Type 1 diabetes (T1D). T1D is thought to arise from selective immunologically mediated destruction of the insulin- producing β-cells in the pancreatic islets of Langerhans with consequent insulin deficiency. It is evident that type 1 diabetes can be conquered, by 1) to stop immune destruction of βcells, 2) to replace or regenerate β-cells, and 3) to preserve β-cell function and mass. Many studies found that the regulatory T cells (Tregs) are crucial for the maintenance of immunological tolerance. Immune tolerance is liable for the activation of the Th1 response. The important role of Th1 response in pathology of T1D entails the depletion of CD4+ T cells, which initiated the use of anti-CD4 monoclonal antibodies (mAbs) against CD4+ T cells to interfere with induction of T1D.Insulin is regulated by Glucagon-Like Peptide-1 hormone (GLP-1) which also stimulates β-cells proliferation as the half-life of GLP-1 harmone is less due to rapid degradation by DPP-IV enzyme an alternative DPP-IV-inhibitors can increase the half-life of GLP-1 through which it conquers the replacement and reserve β-cells mass. Thus in the present study Anti-CD4 mAb was conjugated with Sitagliptin which is a DPP-IV inhibitor Drug loaded in Nanoparticles through Sulfo-MBS cross-linkers. The above study can be an effective approach for treatment to overcome the Passive subcutaneous insulin therapy.

Keywords: antibody drug conjugates, anti-CD4 Mab, DPP IV inhibitors, GLP-1

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Authors: Shraddha Gopal, Jayam Lazarus

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Aims: To study the referral practice and impact of DAT-scan in the diagnosis or exclusion of Parkinson’s disease. Settings and Designs: A retrospective study Materials and methods: A retrospective study of the results of 60 patients who were referred for a DAT scan over a period of 2 years from the Department of Neurology at Northern Lincolnshire and Goole NHS trust. The reason for DAT scan referral was noted under 5 categories against Parkinson’s disease; drug-induced Parkinson’s, essential tremors, diagnostic dilemma, not responding to Parkinson’s treatment, and others. We assessed the number of patients who were diagnosed with Parkinson’s disease against the number of patients in whom Parkinson’s disease was excluded or an alternative diagnosis was made. Statistical methods: Microsoft Excel was used for data collection and statistical analysis, Results: 30 of the 60 scans were performed to confirm the diagnosis of early Parkinson’s disease, 13 were done to differentiate essential tremors from Parkinsonism, 6 were performed to exclude drug-induced Parkinsonism, 5 were done to look for alternative diagnosis as the patients were not responding to anti-Parkinson medication and 6 indications were outside the recommended guidelines. 55% of cases were confirmed with a diagnosis of Parkinson’s disease. 43.33% had Parkinson’s disease excluded. 33 of the 60 scans showed bilateral abnormalities and confirmed the clinical diagnosis of Parkinson’s disease. Conclusion: DAT scan provides valuable information in confirming Parkinson’s disease in 55% of patients along with excluding the diagnosis in 43.33% of patients aiding an alternative diagnosis.

Keywords: DATSCAN, Parkinson's disease, diagnosis, essential tremors

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Authors: Osman Turkoglu, Alvin Estilo, Ritu Gupta, Liliam Pineda-Salgado, Rajesh Pandey

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Background: Hepatotoxicity can be linked to a variety of clinical symptoms and histopathological signs, posing a great challenge in the surveillance of suspected drug-induced liver injury (DILI) cases in the safety database. Additionally, the majority of such cases are rare, idiosyncratic, highly unpredictable, and tend to demonstrate unique individual susceptibility; these qualities, in turn, lend to a pharmacovigilance monitoring process that is often tedious and time-consuming. Objective: Develop a multifactorial algorithm to assist pharmacovigilance physicians in identifying high-risk hepatotoxicity cases associated with DILI from the sponsor’s safety database (Argus). Methods: Multifactorial selection criteria were established using Structured Query Language (SQL) and the TIBCO Spotfire® visualization tool, via a combination of word fragments, wildcard strings, and mathematical constructs, based on Hy’s law criteria and pattern of injury (R-value). These criteria excluded non-eligible cases from monthly line listings mined from the Argus safety database. The capabilities and limitations of these criteria were verified by comparing a manual review of all monthly cases with system-generated monthly listings over six months. Results: On an average, over a period of six months, the algorithm accurately identified 92% of DILI cases meeting established criteria. The automated process easily compared liver enzyme elevations with baseline values, reducing the screening time to under 15 minutes as opposed to multiple hours exhausted using a cognitively laborious, manual process. Limitations of the algorithm include its inability to identify cases associated with non-standard laboratory tests, naming conventions, and/or incomplete/incorrectly entered laboratory values. Conclusions: The newly developed multifactorial algorithm proved to be extremely useful in detecting potential DILI cases, while heightening the vigilance of the drug safety department. Additionally, the application of this algorithm may be useful in identifying a potential signal for DILI in drugs not yet known to cause liver injury (e.g., drugs in the initial phases of development). This algorithm also carries the potential for universal application, due to its product-agnostic data and keyword mining features. Plans for the tool include improving it into a fully automated application, thereby completely eliminating a manual screening process.

Keywords: automation, drug-induced liver injury, pharmacovigilance, post-marketing

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Authors: Qiang Fu, Abu Saleh

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Research studies are highly fragmented when an innovation management framework is being discussed. With the aim to identify an innovation management framework/assessment tool suitable for small & medium enterprises (SMEs) in the service industry, this researcher critically reviewed existing innovation management frameworks and assessment models/tools and discovered a number of literature gaps. It is established that existing literature lacks generally agreed innovation management dimensions, commonly accepted knowledge creation through empirical studies on innovation management in SMEs, effective innovation management performance measurements, and studies on innovation management in the service industry, in particular in retail SMEs. As such, there is a dire need to develop an appropriate firm-level innovation management framework suitable for SMEs in the service industry for a future research project and further study. In addition, this researcher also discussed the significance of establishing such an innovation management framework.

Keywords: innovation management, innovation management framework, innovation management assessment tools, SMEs, service industry

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Authors: Francesca Lombardi, Francesca Rosaria Augello, Benedetta Cinque, Maria Grazia Cifone, Paola Palumbo

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Glioblastoma multiforme (GBM) is a high-grade primary brain tumor refractory to current forms of treatment. The survival benefits of patients with GBM remain unsatisfactory due to the intrinsic or acquired resistance to temozolomide (TMZ), an alkylating agent, used as the first-line chemotherapeutic drug to treat GBM patients. Its cytotoxic effect is visualized by the induction of O6-methylguanine (O6MeG) within DNA. Cyclooxygenase-2 (COX-2), an inflammation-associated enzyme, has been implicated in tumorigenesis and progression of GBM, its inhibition shows anticancer activities. In the present study, it was verified if the combination of a COX-2 selective inhibitor, NS398, with TMZ could counteract the TMZ resistance. In particular, the effect of NS398 mixed with TMZ was investigated in the GBM TMZ-resistant cell line, T98G. Cells were pretreated with NS398 (100µM, 24 hours) and then exposed to TMZ alone (200µM), NS398 alone, or both for 72 hours, after which cell growth rate and cycle phases, as well as apoptosis level, were evaluated. Coadministration of NS398 and TMZ caused a significant decrease in cell growth and a progressive increase of dead cells detected by trypan blue staining. Moreover, a significant level of apoptotic cell percentage and alteration of cell cycle phases were observed in T98G treated with TMZ-NS398 combination when compared to untreated cells or TMZ-treated cells. TMZ-resistant tumors, as GBM, express elevated levels of DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT). The mixture drastically reduced MGMT expression in the TMZ-resistant cell line T98G, known to express high levels of MGMT basically. Moreover, while TMZ alone did not influence the COX-2 protein expression, the combination successfully reduced it. In conclusion, these results demonstrated that NS398 enhanced the efficacy of TMZ through cell number reduction, apoptosis induction, and decreased MGMT levels, suggesting the ability of drug combination to reduce the chemoresistance. This drug combination deserves attention and could be considered as a promising therapeutic strategy for GBM patients.

Keywords: COX-2, COX-2 inhibitor, glioblastoma, NS398, T98G, temozolomide

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Authors: Christina Williams, Mehari Weldemariam, Ann M. Farese, Thomas J. MacVittie, Maureen A. Kane

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Radiation exposure results in dose-dependent and time-dependent multi-organ damage. Drug development of medical countermeasures (MCM) for radiation-induced injury occurs under the FDA Animal Rule because human efficacy studies are not ethical or feasible. The FDA Animal Rule requires the representation of both sexes and describes several uses for biomarkers in MCM drug development studies. Currently, MCMs are limited and there is no FDA-approved biomarker for any radiation injury. Sex as a variable is essential to identifying biomarkers and developing effective MCMs for acute radiation exposure (ARS) and delayed effects of acute radiation exposure (DEARE). These studies aim to address the death of information on sex differences that have not been determined by studies that included only male, single-sex cohorts. Studies have reported differences in radiosensitivity according to sex. As such, biomarker discovery for radiation-induced damage must consider sex as a variable. This study evaluated the plasma proteomic profile of Rhesus macaque non-human primates after different exposures and doses, as well as time points after radiation. Exposures and doses included total body irradiation between 5-7.5 Gy and partial body irradiation with 5% bone marrow sparing at 9, 9.5 and 10 Gy. Timepoints after irradiation included days 1, 3, 60, and 180, which encompassed both acute radiation syndromes and delayed effects of acute radiation exposure. Bottom-up proteomic analyses of plasma included equal numbers of males and females. In the control animals, few proteomic differences are observed between the sexes. In the irradiated animals, there are a few sex differences, with changes mostly consisting of proteins upregulated in the female animals. Multiple canonical pathways were upregulated in irradiated animals relative to the control animals when subjected to pathway analysis, but differential responses between the sexes are limited. These data provide critical baseline differences according to sex and establish sex differences in non-human primate models relevant to drug development of MCM under the FDA Animal Rule.

Keywords: ionizing radiation, sex differences, plasma proteomics, biomarker discovery

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Authors: Ali Kazemi

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The digital evolution of financial services, while offering unprecedented convenience and accessibility, has also escalated the vulnerabilities to fraudulent activities. In this study, we introduce a distinct approach to real-time anomaly detection in financial transactions, aiming to fortify the defenses of banking and financial institutions against such threats. Utilizing unsupervised machine learning algorithms, specifically autoencoders and isolation forests, our research focuses on identifying irregular patterns indicative of fraud within transactional data, thus enabling immediate action to prevent financial loss. The data we used in this study included the monetary value of each transaction. This is a crucial feature as fraudulent transactions may have distributions of different amounts than legitimate ones, such as timestamps indicating when transactions occurred. Analyzing transactions' temporal patterns can reveal anomalies (e.g., unusual activity in the middle of the night). Also, the sector or category of the merchant where the transaction occurred, such as retail, groceries, online services, etc. Specific categories may be more prone to fraud. Moreover, the type of payment used (e.g., credit, debit, online payment systems). Different payment methods have varying risk levels associated with fraud. This dataset, anonymized to ensure privacy, reflects a wide array of transactions typical of a global banking institution, ranging from small-scale retail purchases to large wire transfers, embodying the diverse nature of potentially fraudulent activities. By engineering features that capture the essence of transactions, including normalized amounts and encoded categorical variables, we tailor our data to enhance model sensitivity to anomalies. The autoencoder model leverages its reconstruction error mechanism to flag transactions that deviate significantly from the learned normal pattern, while the isolation forest identifies anomalies based on their susceptibility to isolation from the dataset's majority. Our experimental results, validated through techniques such as k-fold cross-validation, are evaluated using precision, recall, and the F1 score alongside the area under the receiver operating characteristic (ROC) curve. Our models achieved an F1 score of 0.85 and a ROC AUC of 0.93, indicating high accuracy in detecting fraudulent transactions without excessive false positives. This study contributes to the academic discourse on financial fraud detection and provides a practical framework for banking institutions seeking to implement real-time anomaly detection systems. By demonstrating the effectiveness of unsupervised learning techniques in a real-world context, our research offers a pathway to significantly reduce the incidence of financial fraud, thereby enhancing the security and trustworthiness of digital financial services.

Keywords: anomaly detection, financial fraud, machine learning, autoencoders, isolation forest, transactional data analysis

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Authors: Poramet Saeng-On

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This research aims to develop ways of lodging business management of Bang Khonthi community in Samut Songkram province that are appropriate with the cultural context of the Bang Khonthi community. Eight lodging business owners were interviewed. It was found that lodging business that are family business must be done with passion, correct understanding of self, culture, nature, Thai way of life, thorough, professional development, environmentally concerned, building partnerships with various networks both community level, and public sector and business cohorts. Public relations should be done through media both traditional and modern outlets, such as websites and social networks to provide customers convenience, security, happiness, knowledge, love and value when travel to Bang Khonthi. This will also help them achieve sustainability in business, in line with the 10 Home Stay Standard Thailand. Suggestions for operators are as follows: Operators need to improve their public relations work. They need to use technology in public relations such as the internet. Management standards must be improved. Souvenir and local products shops should be arranged in the compound. Product pricing must be set accordingly. They need to join hands to help each other. Quality of the business operation should be raised to meet the standards. Educational measures to reduce the impact caused by tourism on the community such as efforts to reduce energy consumption.

Keywords: homestay, lodging business, management, standard

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Authors: Prakash Singh

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In this exploratory qualitative case study, the voices of female teachers are captured that describe their fear of failure in coping with their daily anxieties, stresses, and tensions in their classrooms. When teachers are usually appointed, the curriculum forms the heart of all their professional obligations. The policy of quality and equality of education for all learners is a must as part of these deliberations, otherwise it would spell the inevitable failure for teachers. Yet, how often have teachers been asked whether they are happy during their professional tenure. Research affirms that this question is not a priority, seeing that the happiness of learners and the educational administrators enjoy precedence. Teachers are often subject to undue pressures and tensions because of environmental factors that extends beyond the curriculum. School violence, bullying, drug abuse, and gangsters are not uncommon to the school milieu, no matter where such schools can be located. In this case study, the voices of female teachers find space concerning their experiences of tobephobia (TBP). The questions that inevitably arise are: Are the educational authorities aware of the effects of TBP in education? What can be done to arrest and eliminate the debilitating effects of TBP? This exploratory study contributes to the growing concerns of TBP in education. It is therefore imperative that the effects of TBP on human resources in education must be accentuated so that meaningful solutions can be found to address challenging educational issues such as school violence, bullying, and drug abuse amongst learners.

Keywords: curriculum, female teachers, school violence, tobephobia

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Authors: Shan-Ying Wu, Sheng-Hui Lan, Xi-Zhang Lin, Ih-Jen Su, Ting-Fen Tsai, Chia-Jui Yen, Tsung-Hsueh Lu, Fu-Wen Liang, Huey-Jen Su, Chun-Li Su, Hsiao-Sheng Liu

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In hepatocelluar carcinoma (HCC), dysregulated expression of cyclin D1 and impaired autophagy has been reported separately. However, the relationship between them has not been explored. In this study, we demonstrated that autophagy was inversely correlated with cyclin D1 expression in 147 paired HCC patient specimens. HCC specimen with highly expression of cyclin D1 shows correlation with poor overall survival rate. Furthermore, induction of autophagy by amiodarone (antiarrhythmic drug) in Hep 3B cells, cyclin D1 was recruited into autophagosomes demonstrated by immune-gold labeling of cyclin D1 after extraction of autophagosomes. We further demonstrated that autophagy suppresses Hep 3B cell proliferation, and further analysis revealed that cell cycle was arrested at G1 phase. The interaction between LC3 (maker of autophagy) and cyclin D1 was increased after autophagy induction. In addition, ubiquitinated-cyclin D1 was also increased after autophagy induction, which is selectively degraded by autophagosome through binding with SQSTM1/p62 (an adaptor protein). In vivo study showed that amiodarone induced autophagy suppresses liver tumor formation in xenograft mouse and orthotopic rat model through decreasing cyclin D1 expression and inhibition of cell proliferation. Altogether, we reveal a novel mechanism that ubiquitinated cyclin D1 degraded by autophagic pathway by p62 and amiodarone is a promising drug for targeting cyclin D1 in liver cancer therapy.

Keywords: autophagy, cyclin D1, hepatocellular carcinoma, amiodarone

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Authors: Si On Na

Abstract:

The development of American radio and print media since World War II has allowed people with disabilities to engage more directly with the public, gradually changing the perception that disabled people constitute a kind of social impairment or burden. People with disabilities have rarely been portrayed as equal to the non-disabled. In the postwar period, a dramatic shift from eugenicist conceptualizations of disability and widespread institutionalization gradually evolved into conditions of greater openness in public discourse. This discourse was marked at mid-century by telethons and news media (both print and television) which sought to commodify people with disabilities for commercial gain through stories that promoted alienating forms of empowerment alternating with paternalistic pity. By comparing studies of the history of American disability advocacy in the twentieth century and the evolution of the image of disability characteristic of mid-century media discourse, this paper will examine the relationship between the passage of the American with Disabilities Act of 1990 (ADA) and the expanded media representation of people with disabilities. This paper will argue that the legal mandate of the ADA ultimately transformed the image of people with disabilities from those who are weak and in need of support to viable consumers, encouraging traditional American print, film, and television media outlets to solicit the agency of people with disabilities in the authentic portrayal of themselves and their disabilities.

Keywords: ADA, disability representation, media portrayal, postwar United States

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Authors: A. Alyami, S. Christmas, K. Neeltje, G. Pollakis, B. Paxton, Z. Al-Bayati

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The Human leukocyte antigen-G (HLA-G) molecule plays an important role in immunomodulation. To date, 16 untranslated regions (UTR) HLA-G haplotypes have been previously defined by sequenced SNPs in the coding region. From these, UTR-1, UTR-2, UTR-3, UTR-4, UTR-5, UTR-6 and UTR-7 are the most frequent 3’UTR haplotypes at the global level. UTR-1 is associated with higher levels of soluble HLA-G and HLA-G expression, whereas UTR-5 and UTR-7 are linked with low levels of soluble HLA-G and HLA-G expression. Human immunodeficiency virus type 1 (HIV-1) infection results in the progressive loss of immune function in infected individuals. The virus escape mechanism typically includes T lymphocytes and NK cell recognition and lyses by classical HLA-A and B down-regulation, which has been associated with non-classical HLA-G molecule up-regulation, respectively. We evaluated the haplotypes of the HLA-G 3′ untranslated region frequencies observed in three HIV-1 groups from the Netherlands and their susceptibility to develop infection. The three groups are made up of mainly men who have sex with men (MSM), injection drug users (IDU) and a high-risk-seronegative (HRSN) group. DNA samples were amplified with published primers prior sequencing. According to our results, the low expresser frequencies show higher in HRSN compared to other groups. This is indicating that 3’UTR polymorphisms may be identified as potential prognostic biomarkers to determine susceptibility to HIV.

Keywords: Human leukocyte antigen-G (HLA-G) , men who have sex with men (MSM), injection drug users (IDU), high-risk-seronegative (HRSN) group, high-untranslated region (UTR)

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