Search results for: stimuli-responsive drug delivery
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3478

Search results for: stimuli-responsive drug delivery

2428 Understanding the Mechanisms of Salmonella Typhimurium Resistance to Cannabidiol (CDB)

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

Abstract:

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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2427 Getting It Right Before Implementation: Using Simulation to Optimize Recommendations and Interventions After Adverse Event Review

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

Abstract:

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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2426 Magnetohemodynamic of Blood Flow Having Impact of Radiative Flux Due to Infrared Magnetic Hyperthermia: Spectral Relaxation Approach

Authors: Ebenezer O. Ige, Funmilayo H. Oyelami, Joshua Olutayo-Irheren, Joseph T. Okunlola

Abstract:

Hyperthermia therapy is an adjuvant procedure during which perfused body tissues is subjected to elevated range of temperature in bid to achieve improved drug potency and efficacy of cancer treatment. While a selected class of hyperthermia techniques is shouldered on the thermal radiations derived from single-sourced electro-radiation measures, there are deliberations on conjugating dual radiation field sources in an attempt to improve the delivery of therapy procedure. This paper numerically explores the thermal effectiveness of combined infrared hyperemia having nanoparticle recirculation in the vicinity of imposed magnetic field on subcutaneous strata of a model lesion as ablation scheme. An elaborate Spectral relaxation method (SRM) was formulated to handle equation of coupled momentum and thermal equilibrium in the blood-perfused tissue domain of a spongy fibrous tissue. Thermal diffusion regimes in the presence of external magnetic field imposition were described leveraging on the renowned Roseland diffusion approximation to delineate the impact of radiative flux within the computational domain. The contribution of tissue sponginess was examined using mechanics of pore-scale porosity over a selected of clinical informed scenarios. Our observations showed for a substantial depth of spongy lesion, magnetic field architecture constitute the control regimes of hemodynamics in the blood-tissue interface while facilitating thermal transport across the depth of the model lesion. This parameter-indicator could be utilized to control the dispensing of hyperthermia treatment in intravenous perfused tissue.

Keywords: spectra relaxation scheme, thermal equilibrium, Roseland diffusion approximation, hyperthermia therapy

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2425 How the Current Opioid Crisis Differs from the Heroin Epidemic of the 1960s-1970s: An Analysis of Drugs and Demographics

Authors: Donna L. Roberts

Abstract:

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

Procedia PDF Downloads 146
2424 Consumer Welfare in the Platform Economy

Authors: Prama Mukhopadhyay

Abstract:

Starting from transport to food, today’s world platform economy and digital markets have taken over almost every sphere of consumers’ lives. Sellers and buyers are getting connected through platforms, which is acting as an intermediary. It has made consumer’s life easier in terms of time, price, choice and other factors. Having said that, there are several concerns regarding platforms. There are competition law concerns like unfair pricing, deep discounting by the platforms which affect the consumer welfare. Apart from that, the biggest problem is lack of transparency with respect to the business models, how it operates, price calculation, etc. In most of the cases, consumers are unaware of how their personal data are being used. In most of the cases, they are unaware of how algorithm uses their personal data to determine the price of the product or even to show the relevant products using their previous searches. Using personal or non-personal data without consumer’s consent is a huge legal concern. In addition to this, another major issue lies with the question of liability. If a dispute arises, who will be responsible? The seller or the platform? For example, if someone ordered food through a food delivery app and the food was bad, in this situation who will be liable: the restaurant or the food delivery platform? In this paper, the researcher tries to examine the legal concern related to platform economy from the consumer protection and consumer welfare perspectives. The paper analyses the cases from different jurisdictions and approach taken by the judiciaries. The author compares the existing legislation of EU, US and other Asian Countries and tries to highlight the best practices.

Keywords: competition, consumer, data, platform

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2423 Impact of the Hayne Royal Commission on the Operating Model of Australian Financial Advice Firms

Authors: Mohammad Abu-Taleb

Abstract:

The final report of the Royal Commission into Australian financial services misconduct, released in February 2019, has had a significant impact on the financial advice industry. The recommendations released in the Commissioner’s final report include changes to ongoing fee arrangements, a new disciplinary system for financial advisers, and mandatory reporting of compliance concerns. This thesis aims to explore the impact of the Royal Commission’s recommendations on the operating model of financial advice firms in terms of advice products, processes, delivery models, and customer segments. Also, this research seeks to investigate whether the Royal Commission’s outcome has accelerated the use of enhanced technology solutions within the operating model of financial advice firms. And to identify the key challenges confronting financial advice firms whilst implementing the Commissioner’s recommendations across their operating models. In order to achieve the objectives of this thesis, a qualitative research design has been adopted through semi-structured in-depth interviews with 24 financial advisers and managers who are engaged in the operation of financial advice services. The study used the thematic analysis approach to interpret the qualitative data collected from the interviews. The findings of this thesis reveal that customer-centric operating models will become more prominent across the financial advice industry in response to the Commissioner’s final report. And the Royal Commission’s outcome has accelerated the use of advice technology solutions within the operating model of financial advice firms. In addition, financial advice firms have started more than before using simpler and more automated web-based advice services, which enable financial advisers to provide simple advice in a greater scale, and also to accelerate the use of robo-advice models and digital delivery to mass customers in the long term. Furthermore, the study identifies process and technology changes as, long with technical and interpersonal skills development, as the key challenges encountered financial advice firms whilst implementing the Commissioner’s recommendations across their operating models.

Keywords: hayne royal commission, financial planning advice, operating model, advice products, advice processes, delivery models, customer segments, digital advice solutions

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2422 Effect on Tolerability and Adverse Events in Participants Receiving Naltrexone/Bupropion and Antidepressant Medication, Including SSRIs, in a Large Randomized Double-Blind Study

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

Abstract:

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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2421 Tranexamic Acid in Prevention of Postpartum Haemorrhage in Elective Cesarean Section

Authors: Ajay Agrawal, Pravin Shah, Shailaja Chhetri, Pappu Rijal

Abstract:

Background and Objectives: Postpartum hemorrhage (PPH) is a common and occasionally life-threatening complication of labour. Cesarean section (CS) is associated with more blood loss than vaginal delivery. There is a trend for increasing CS rates in both developed and developing countries. This could increase the risk of morbidity and mortality, especially among anemic women. The objective of this study was to evaluate the effect of preoperative administration of Intravenous Tranexamic Acid (TA) on blood loss during and after elective CS delivery. Materials and Methods: It is a prospective, randomized controlled study. 160 eligible pregnant women of 37 or more POG planned for CS were randomized into two groups either to receive 10ml(1gm) of tranexamic acid intravenously or 10ml of normal saline. Blood loss was measured during and for 24 hours after operation. Results: The mean estimated blood loss was significantly lower in women treated with TA compared with women in the placebo group (392.13 ml ± 10.06 versus 498.69 ml ± 15.87, respectively; p < 0.001). The mean difference in pre-operative and post-operative hemoglobin levels was statistically significant in the tranexamic acid group than in the control group (0.31 ± 0.18 versus 0.79 ± 0.23, respectively; p < 0.001). Conclusion: Pre-operative use of tranexamic acid is associated with reduced blood loss during and after elective cesarean section. In a developing country like ours where PPH is a major threat to the life of the mothers, it seems to be a promising option.

Keywords: blood loss, cesarean section, postpartum hemorrhage, tranexamic acid

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2420 Metal-Organic Frameworks for Innovative Functional Textiles

Authors: Hossam E. Emam

Abstract:

Metal–organic frameworks (MOFs) are new hybrid materials investigated from 15 years ago; they synthesized from metals as inorganic center joined with multidentate organic linkers to form a 1D, 2D or 3D network structure. MOFs have unique properties such as pore crystalline structure, large surface area, chemical tenability and luminescent characters. These significant properties enable MOFs to be applied in many fields such like gas storage, adsorption/separation, drug delivery/biomedicine, catalysis, polymerization, magnetism and luminescence applications. Recently, many of published reports interested in superiority of MOFs for functionalization of textiles to exploit the unique properties of MOFs. Incorporation of MOFs is found to acquire the textiles some additional formidable functions to be used in considerable fields such like water treatment and fuel purification. Modification of textiles with MOFs could be easily performed by two main techniques; Ex-situ (preparation of MOFs then applied onto textiles) and in-situ (ingrowth of MOFs within textiles networks). Uniqueness of MOFs could be assimilated in acquirement of decorative color, antimicrobial character, anti-mosquitos character, ultraviolet radiation protective, self-clean, photo-luminescent and sensor character. Additionally, textiles treatment with MOFs make it applicable as filter in the adsorption of toxic gases, hazardous materials (such as pesticides, dyes and aromatics molecules) and fuel purification (such as removal of oxygenated, nitrogenated and sulfur compounds). Also, the porous structure of MOFs make it mostly utilized in control release of insecticides from the surface of the textile. Moreover, MOF@textiles as recyclable materials lead it applicable as photo-catalyst composites for photo-degradation of different dyes in the day light. Therefore, MOFs is extensively considered for imparting textiles with formidable properties as ingeniousness way for textile functionalization.

Keywords: MOF, functional textiles, water treatment, fuel purification, environmental applications

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2419 An Empirical Analysis of the Determinants for Adopting Vocera Wireless Communication Systems

Authors: Patrick David Chirilele

Abstract:

There are growing interests in improving service delivery in the healthcare sector through the adoption of emerging digital technologies, including the Vocera B3000n communication system badge. As a result, understanding the factors that impact the adoption of such digital technologies is becoming important. This study investigates the determinants of task-technology fit through the adoption of Vocera B3000n communication system badge in healthcare sector in South Africa. Statistical analyses are performed on the data collected from 143 healthcare workers including registered nurses and personal care workers at three hospitals in South Africa through survey to test the relationship between task characteristics, technology characteristics and user characteristics for better understanding the task-technology fit and the adoption of Vocera communication systems in South African hospitals. The result reveals that all three factors have a significant impact on task-technology fit through the adoption of Vocera B3000n communication system badge. Such findings are useful for healthcare sector in their adoption of digital technologies for improving service delivery through effective communication in their workplace.

Keywords: adoption, communication systems, task-technology fit, user characteristics, Vocera

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2418 Evaluation of Critical Success Factors in Public-Private Partnership Projects Based on Structural Equation Model

Authors: Medya Fathi

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Today, success in the construction industry is not merely about project completion in a timely manner within an established budget and meeting required quality considerations. Management practices and partnerships need to be emphasized as well. In this regard, critical success factors (CSFs) cover necessary considerations for a successful project beyond the traditional success definition, which vary depending on project outcomes, delivery methods, project types, and partnering processes. Despite the extensive research on CSFs, there is a paucity of studies that examine CSFs for public-private partnership (PPP); the delivery method, which has gained increasing attention from researchers and practitioners over the last decade with a slow but growing adoption in the transportation infrastructure, particularly, highway industry. To fill this knowledge gap, data are collected through questionnaire surveys among private and public parties involved in PPP transportation projects in the United States. Then, the collected data are analyzed to explore the causality relationships between CSFs and PPP project success using structural equation model and provide a list of factors with the greatest influence. This study advocates adopting a critical success factor approach to enhance PPP success in the U.S. transportation industry and identify elements essential for public and private organizations to achieve this success.

Keywords: project success, critical success factors, public-private partnership, transportation

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2417 Effect of Surfactant Level of Microemulsions and Nanoemulsions on Cell Viability

Authors: Sonal Gupta, Rakhi Bansal, Javed Ali, Reema Gabrani, Shweta Dang

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Nanoemulsions (NEs) and microemulsions (MEs) have been an attractive tool for encapsulation of both hydrophilic and lipophillic actives. Both these systems are composed of oil phase, surfactant, co-surfactant and aqueous phase. Depending upon the application and intended use, both oil-in-water and water-in-oil emulsions can be designed. NEs are fabricated using high energy methods employing less percentage of surfactant as compared to MEs which are self assembled drug delivery systems. Owing to the nanometric size of the droplets these systems have been widely used to enhance solubility and bioavailability of natural as well as synthetic molecules. The aim of the present study is to assess the effect of % age of surfactants on cell viability of Vero cells (African Green Monkeys’ Kidney epithelial cells) via MTT assay. Green tea catechin (Polyphenon 60) loaded ME employing low energy vortexing and NE employing high energy ultrasonication were prepared using same excipients (labrasol as oil, cremophor EL as surfactant and glycerol as co-surfactant) however, the % age of oil and surfactant needed to prepare the ME was higher as compared to NE. These formulations along with their excipients (oilME=13.3%, SmixME=26.67%; oilNE=10%, SmixNE=13.52%) were added to Vero cells for 24 hrs. The tetrazolium dye, 3-(4,5-dimethylthia/ol-2-yl)-2,5-diphi-iiyltclrazolium bromide (MTT), is reduced by live cells and this reaction is used as the end point to evaluate the cytoxicity level of a test formulation. Results of MTT assay indicated that oil at different percentages exhibited almost equal cell viability (oilME ≅ oilNE) while surfactant mixture had a significant difference in the cell viability values (SmixME < SmixNE). Polyphenon 60 loaded ME and its PlaceboME showed higher toxicity as compared to Polyphenon 60 loaded NE and its PlaceboNE that can be attributed to the higher concentration of surfactants present in MEs. Another probable reason for high % cell viability of Polyphenon 60 loaded NE might be due to the effective release of Polyphenon 60 from NE formulation that helps in the sustenance of Vero cells.

Keywords: cell viability, microemulsion, MTT, nanoemulsion, surfactants, ultrasonication

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2416 Drugstore Control System Design and Realization Based on Programmable Logic Controller (PLC)

Authors: Muhammad Faheem Khakhi, Jian Yu Wang, Salman Muhammad, Muhammad Faisal Shabir

Abstract:

Population growth and Chinese two-child policy will boost pharmaceutical market, and it will continue to maintain the growth for a period of time in the future, the traditional pharmacy dispensary has been unable to meet the growing medical needs of the peoples. Under the strong support of the national policy, the automatic transformation of traditional pharmacies is the inclination of the Times, the new type of intelligent pharmacy system will continue to promote the development of the pharmaceutical industry. Under this background, based on PLC control, the paper proposed an intelligent storage and automatic drug delivery system; complete design of the lower computer's control system and the host computer's software system has been present. The system can be applied to dispensing work for Chinese herbal medicinal and Western medicines. Firstly, the essential of intelligent control system for pharmacy is discussed. After the analysis of the requirements, the overall scheme of the system design is presented. Secondly, introduces the software and hardware design of the lower computer's control system, including the selection of PLC and the selection of motion control system, the problem of the human-computer interaction module and the communication between PC and PLC solves, the program design and development of the PLC control system is completed. The design of the upper computer software management system is described in detail. By analyzing of E-R diagram, built the establish data, the communication protocol between systems is customize, C++ Builder is adopted to realize interface module, supply module, main control module, etc. The paper also gives the implementations of the multi-threaded system and communication method. Lastly, each module of the lower computer control system is tested. Then, after building a test environment, the function test of the upper computer software management system is completed. On this basis, the entire control system accepts the overall test.

Keywords: automatic pharmacy, PLC, control system, management system, communication

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2415 Monitoring the Thin Film Formation of Carrageenan and PNIPAm Microgels

Authors: Selim Kara, Ertan Arda, Fahrettin Dolastir, Önder Pekcan

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Biomaterials and thin film coatings play a fundamental role in medical, food and pharmaceutical industries. Carrageenan is a linear sulfated polysaccharide extracted from algae and seaweeds. To date, such biomaterials have been used in many smart drug delivery systems due to their biocompatibility and antimicrobial activity properties. Poly (N-isopropylacrylamide) (PNIPAm) gels and copolymers have also been used in medical applications. PNIPAm shows lower critical solution temperature (LCST) property at about 32-34 °C which is very close to the human body temperature. Below and above the LCST point, PNIPAm gels exhibit distinct phase transitions between swollen and collapsed states. A special class of gels are microgels which can react to environmental changes significantly faster than microgels due to their small sizes. Quartz crystal microbalance (QCM) measurement technique is one of the attractive techniques which has been used for monitoring the thin-film formation process. A sensitive QCM system was designed as to detect 0.1 Hz difference in resonance frequency and 10-7 change in energy dissipation values, which are the measures of the deposited mass and the film rigidity, respectively. PNIPAm microgels with the diameter around few hundred nanometers in water were produced via precipitation polymerization process. 5 MHz quartz crystals with functionalized gold surfaces were used for the deposition of the carrageenan molecules and microgels in the solutions which were slowly pumped through a flow cell. Interactions between charged carrageenan and microgel particles were monitored during the formation of the film layers, and the Sauerbrey masses of the deposited films were calculated. The critical phase transition temperatures around the LCST were detected during the heating and cooling cycles. It was shown that it is possible to monitor the interactions between PNIPAm microgels and biopolymer molecules, and it is also possible to specify the critical phase transition temperatures by using a QCM system.

Keywords: carrageenan, phase transitions, PNIPAm microgels, quartz crystal microbalance (QCM)

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2414 Investigation of Carbapenem-Resistant Genes in Acinetobacter spp. Isolated from Patients at Tertiary Health Care Center, Northeastern Thailand

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

Abstract:

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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2413 Secured Cancer Care and Cloud Services in Internet of Things /Wireless Sensor Network Based Medical Systems

Authors: Adeniyi Onasanya, Maher Elshakankiri

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In recent years, the Internet of Things (IoT) has constituted a driving force of modern technological advancement, and it has become increasingly common as its impacts are seen in a variety of application domains, including healthcare. IoT is characterized by the interconnectivity of smart sensors, objects, devices, data, and applications. With the unprecedented use of IoT in industrial, commercial and domestic, it becomes very imperative to harness the benefits and functionalities associated with the IoT technology in (re)assessing the provision and positioning of healthcare to ensure efficient and improved healthcare delivery. In this research, we are focusing on two important services in healthcare systems, which are cancer care services and business analytics/cloud services. These services incorporate the implementation of an IoT that provides solution and framework for analyzing health data gathered from IoT through various sensor networks and other smart devices in order to improve healthcare delivery and to help health care providers in their decision-making process for enhanced and efficient cancer treatment. In addition, we discuss the wireless sensor network (WSN), WSN routing and data transmission in the healthcare environment. Finally, some operational challenges and security issues with IoT-based healthcare system are discussed.

Keywords: IoT, smart health care system, business analytics, (wireless) sensor network, cancer care services, cloud services

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2412 Impact of Flexibility on Patient Satisfaction and Behavioral Intention: A Critical Reassessment and Model Development

Authors: Pradeep Kumar, Shibashish Chakraborty, Sasadhar Bera

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In the anticipation of demand fluctuations, services cannot be inventoried and hence it creates a difficult problem in marketing of services. The inability to meet customers (patients) requirements in healthcare context has more serious consequences than other service sectors. In order to meet patient requirements in the current uncertain environment, healthcare organizations are seeking ways for improved service delivery. Flexibility provides a mechanism for reducing variability in service encounters and improved performance. Flexibility is defined as the ability of the organization to cope with changing circumstances or instability caused by the environment. Patient satisfaction is an important performance outcome of healthcare organizations. However, the paucity of information exists in healthcare delivery context to examine the impact of flexibility on patient satisfaction and behavioral intention. The present study is an attempt to develop a conceptual foundation for investigating overall impact of flexibility on patient satisfaction and behavioral intention. Several dimensions of flexibility in healthcare context are examined and proposed to have a significant impact on patient satisfaction and intention. Furthermore, the study involves a critical examination of determinants of patient satisfaction and development of a comprehensive view the relationship between flexibility, patient satisfaction and behavioral intention. Finally, theoretical contributions and implications for healthcare professionals are suggested from flexibility perspective.

Keywords: healthcare, flexibility, patient satisfaction, behavioral intention

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2411 Sitagliptin-AntiCD4 Mab Conjugated T Cell Targeting Therapy for the Effective Treatment of Type I Diabetes

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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2410 Role of DatScan in the Diagnosis of Parkinson's Disease

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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2409 The Anti-Bladder Cancer Effects Exerted by Hyaluronan Nanoparticles Encapsulated Heteronemin Isolated from Hippospongia Sp.

Authors: Kuan Yin Hsiao, Shyh Ming Kuo, Yi Jhen Wu, Chin Wen Chuang, Chuen-Fu Lin, Wei-qing Yang, Han Hsiang Huang

Abstract:

Anti-tumor effects of natural products, like compounds from marine sponges and soft corals, have been investigated for decades. Polymeric nanoparticles prepared from biodegradable and biocompatible molecules, such as Hyaluronan (HA), Chitosan (CHI) and gelatin have been widely studied. Encapsulation of anti-cancer therapies by the biopolymeric nanoparticles in drug delivery system is potentially capable of improving the therapeutic effects and attenuating their toxicity. In the current study, the anti-bladder cancer effects of heteronemin extracted from the sponge Hippospongia sp. with or without HA and CHI nanoparticle encapsulation were assessed and evaluated in vitro. Results showed that IC50 (half maximal inhibitory concentration) of heteronemin toward T24 human bladder cancer cell viability is approximately 0.18 µg/mL. Both plain and HA nanoparticles-encapsulated heteronemin at 0.2 and 0.4 µg/mL significantly reduced T24 cell viability (P<0.001) while HA nanoparticles-encapsulated heteronemin showed weaker viability-inhibitory effects on L929 fibroblasts compared with plain heteronemin at the identical concentrations. HA and CHI nanoparticles-encapsulated heteronemin exhibited significantly stronger inhibitory effects against migration of T24 human bladder cancer cell than those exerted by plain heteronemin at the same concentrations (P<0.001). The flow cytometric results showed that 0.2 µg/mL HA and CHI nanoparticles-encapsulated heteronemin induced higher early apoptosis rate than that induced by plain heteronemin at the same concentration. These results show that HA and CHI nanoparticle encapsulation is able to elevate anti-migratory and apoptosis-inducing effects exerted by heteronemin against bladder cancer cells in vitro. The in vivo anti-bladder cancer effects of the compound with or without HA/CHI nanoparticle encapsulation will be further investigated and examined using murine tumor models. The data obtained from this study will extensively evaluate of the anti-bladder cancer effects of heteronemin as well as HA/CHI-encapsulated heteronemin and pave a way to develop potential bladder cancer treatment.

Keywords: heteronemin, nanoparticles, hyaluronan, chitosan, bladder cancer

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2408 A Multifactorial Algorithm to Automate Screening of Drug-Induced Liver Injury Cases in Clinical and Post-Marketing Settings

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

Abstract:

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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2407 COX-2 Inhibitor NS398 Counteracts Chemoresistance to Temozolomide in T98G Glioblastoma Cell Line

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

Abstract:

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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2406 A Web-Based Real Property Updating System for Efficient and Sustainable Urban Development: A Case Study in Ethiopia

Authors: Eyosiyas Aga

Abstract:

The development of information communication technology has transformed the paper-based mapping and land registration processes to a computerized and networked system. The computerization and networking of real property information system play a vital role in good governance and sustainable development of emerging countries through cost effective, easy and accessible service delivery for the customer. The efficient, transparent and sustainable real property system is becoming the basic infrastructure for the urban development thus improve the data management system and service delivery in the organizations. In Ethiopia, the real property administration is paper based as a result, it confronted problems of data management, illegal transactions, corruptions, and poor service delivery. In order to solve this problem and to facilitate real property market, the implementation of web-based real property updating system is crucial. A web-based real property updating is one of the automation (computerizations) methods to facilitate data sharing, reduce time and cost of the service delivery in real property administration system. In additions, it is useful for the integration of data onto different information systems and organizations. This system is designed by combining open source software which supported by open Geo-spatial consortium. The web-based system is mainly designed by using open source software with the help of open Geo-spatial Consortium. The Open Geo-spatial Consortium standards such as the Web Feature Service and Web Map Services are the most widely used standards to support and improves web-based real property updating. These features allow the integration of data from different sources, and it can be used to maintain consistency of data throughout transactions. The PostgreSQL and Geoserver are used to manage and connect a real property data to the flex viewer and user interface. The system is designed for both internal updating system (municipality); which is mainly updating of spatial and textual information, and the external system (customer) which focus on providing and interacting with the customer. This research assessed the potential of open source web applications and adopted this technology for real property updating system in Ethiopia through simple, cost effective and secured way. The system is designed by combining and customizing open source software to enhance the efficiency of the system in cost effective way. The existing workflow for real property updating is analyzed to identify the bottlenecks, and the new workflow is designed for the system. The requirement is identified through questionnaire and literature review, and the system is prototype for the study area. The research mainly aimed to integrate human resource with technology in designing of the system to reduce data inconsistency and security problems. In additions, the research reflects on the current situation of real property administration and contributions of effective data management system for efficient, transparent and sustainable urban development in Ethiopia.

Keywords: cadaster, real property, sustainable, transparency, web feature service, web map service

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2405 Proteomic Evaluation of Sex Differences in the Plasma of Non-human Primates Exposed to Ionizing Radiation for Biomarker Discovery

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

Abstract:

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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2404 Modeling and Simulation of the Structural, Electronic and Magnetic Properties of Fe-Ni Based Nanoalloys

Authors: Ece A. Irmak, Amdulla O. Mekhrabov, M. Vedat Akdeniz

Abstract:

There is a growing interest in the modeling and simulation of magnetic nanoalloys by various computational methods. Magnetic crystalline/amorphous nanoparticles (NP) are interesting materials from both the applied and fundamental points of view, as their properties differ from those of bulk materials and are essential for advanced applications such as high-performance permanent magnets, high-density magnetic recording media, drug carriers, sensors in biomedical technology, etc. As an important magnetic material, Fe-Ni based nanoalloys have promising applications in the chemical industry (catalysis, battery), aerospace and stealth industry (radar absorbing material, jet engine alloys), magnetic biomedical applications (drug delivery, magnetic resonance imaging, biosensor) and computer hardware industry (data storage). The physical and chemical properties of the nanoalloys depend not only on the particle or crystallite size but also on composition and atomic ordering. Therefore, computer modeling is an essential tool to predict structural, electronic, magnetic and optical behavior at atomistic levels and consequently reduce the time for designing and development of new materials with novel/enhanced properties. Although first-principles quantum mechanical methods provide the most accurate results, they require huge computational effort to solve the Schrodinger equation for only a few tens of atoms. On the other hand, molecular dynamics method with appropriate empirical or semi-empirical inter-atomic potentials can give accurate results for the static and dynamic properties of larger systems in a short span of time. In this study, structural evolutions, magnetic and electronic properties of Fe-Ni based nanoalloys have been studied by using molecular dynamics (MD) method in Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) and Density Functional Theory (DFT) in the Vienna Ab initio Simulation Package (VASP). The effects of particle size (in 2-10 nm particle size range) and temperature (300-1500 K) on stability and structural evolutions of amorphous and crystalline Fe-Ni bulk/nanoalloys have been investigated by combining molecular dynamic (MD) simulation method with Embedded Atom Model (EAM). EAM is applicable for the Fe-Ni based bimetallic systems because it considers both the pairwise interatomic interaction potentials and electron densities. Structural evolution of Fe-Ni bulk and nanoparticles (NPs) have been studied by calculation of radial distribution functions (RDF), interatomic distances, coordination number, core-to-surface concentration profiles as well as Voronoi analysis and surface energy dependences on temperature and particle size. Moreover, spin-polarized DFT calculations were performed by using a plane-wave basis set with generalized gradient approximation (GGA) exchange and correlation effects in the VASP-MedeA package to predict magnetic and electronic properties of the Fe-Ni based alloys in bulk and nanostructured phases. The result of theoretical modeling and simulations for the structural evolutions, magnetic and electronic properties of Fe-Ni based nanostructured alloys were compared with experimental and other theoretical results published in the literature.

Keywords: density functional theory, embedded atom model, Fe-Ni systems, molecular dynamics, nanoalloys

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2403 Voices of Fear: A Case Study Of Tobephobia Experienced by Female Teachers

Authors: Prakash Singh

Abstract:

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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2402 Collaborative Reflexive/Reflective Teaching and Action Research in TESL

Authors: O. F. Elkommos

Abstract:

Teaching English as a Second Language (TESL) has become a very rich area of research. Practitioners or teachers of English as a foreign or a second language are now promoting both collaborative learning and collaborative teaching. Students learning a language collaboratively and cooperatively are learning in a better environment of team work where they learn from each other. Further, teaching English collaboratively also creates an enriching environment that is also very enriching to students’ and teachers’ experiences of learning and teaching. Moreover, action research stems from actual teacher concerns and students’ needs. Reflection in turn, on the experience of the material taught and the delivery of material is becoming an integral part of the teaching and learning experience self- evaluation and self-development. In this case, the concern of the research field in the area of TESL will be the development of teaching delivery, material and quality of learning. In the present research, the TESL module taught to year two students in the Faculty of Arts and Humanities, British University in Egypt (BUE) will be evaluated reflexively by the students and teachers. The module was taught to students in two different specialisms. It was taught and delivered through collaborative teaching and was evaluated by both teachers and students as very successful and enjoyable. The reflections of both teachers and students as well as student results confirm that it was a success.

Keywords: action research, addressing differentiation, collaborative teaching, reflective teaching and learning, reflexive learning, reflexive teaching, self-development, self-evaluation, TESL

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2401 Maternal and Child Health Care: A Study among the Rongmeis of Manipur, India

Authors: Lorho Mary Maheo, Arundhati Maibam Devi

Abstract:

Background: Maternal and child health (MCH) cares are the health services provided to mothers and children. It includes the health promotion, preventive, curative and rehabilitation health care for mothers and children. Materials and method: The present study sample comprises of 208 women within the age range 15-69 years from two remote villages of Tamenglong District in Manipur. They were randomly chosen for assessing their health as well as the child’s health adopting an interview schedule method. Results: The findings of the study revealed that majority (80%) of the women have their first conception in their first year of married life. A decadal change has been observed with regard to the last pregnancy i.e., antenatal check-up, place of delivery as well as the service provider. However, irrespective of age of the women, home delivery is still preferred though very few are locally trained. Pre- and post-delivery resting period vary depending on the busy schedule of the agricultural works as the population under study is basically agriculturist. Postnatal care remains to be traditional as they are strongly associated with cultural beliefs and practices that continue to prevail in the studied community. Breast feeding practices such as colostrums given, initiation of breastfeeding, weaning was all taken into account.  Immunization of children has not reached the expected target owing to a variety of reasons. Maternal health care also includes use of birth control measures. The health status of women would invariably improve if family planning is meaningfully adopted. Only 10.1% of the women adopted the modern birth control implying its deep-rooted value attached to the children. Based on the self-assessment report on their health treatment a good number of the respondents resorted to self-medication even to the extent of buying allopathic medicine without a doctor’s prescription. One important finding from the study is the importance attributed to the traditional health care system which is easily affordable and accessible to the villagers. Conclusion: The overall condition of maternal and child care is way behind till now as no adequate/proper health services are available.

Keywords: antenatal, breastfeeding, child health, maternal, Tamenglong District

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2400 Experimental and Theoretical Characterization of Supramolecular Complexes between 7-(Diethylamino)Quinoline-2(1H)-One and Cucurbit[7] Uril

Authors: Kevin A. Droguett, Edwin G. Pérez, Denis Fuentealba, Margarita E. Aliaga, Angélica M. Fierro

Abstract:

Supramolecular chemistry is a field of growing interest. Moreover, studying the formation of host-guest complexes between macrocycles and dyes is highly attractive due to their potential applications. Examples of the above are drug delivery, catalytic process, and sensing, among others. There are different dyes of interest in the literature; one example is the quinolinone derivatives. Those molecules have good optical properties and chemical and thermal stability, making them suitable for developing fluorescent probes. Secondly, several macrocycles can be seen in the literature. One example is the cucurbiturils. This water-soluble macromolecule family has a hydrophobic cavity and two identical carbonyl portals. Additionally, the thermodynamic analysis of those supramolecular systems could help understand the affinity between the host and guest, their interaction, and the main stabilization energy of the complex. In this work, two 7-(diethylamino) quinoline-2 (1H)-one derivative (QD1-2) and their interaction with cucurbit[7]uril (CB[7]) were studied from an experimental and in-silico point of view. For the experimental section, the complexes showed a 1:1 stoichiometry by HRMS-ESI and isothermal titration calorimetry (ITC). The inclusion of the derivatives on the macrocycle lends to an upward shift in the fluorescence intensity, and the pKa value of QD1-2 exhibits almost no variation after the formation of the complex. The thermodynamics of the inclusion complexes was investigated using ITC; the results demonstrate a non-classical hydrophobic effect with a minimum contribution from the entropy term and a constant binding on the order of 106 for both ligands. Additionally, dynamic molecular studies were carried out during 300 ns in an explicit solvent at NTP conditions. Our finding shows that the complex remains stable during the simulation (RMSD ~1 Å), and hydrogen bonds contribute to the stabilization of the systems. Finally, thermodynamic parameters from MMPBSA calculations were obtained to generate new computational insights to compare with experimental results.

Keywords: host-guest complexes, molecular dynamics, quinolin-2(1H)-one derivatives dyes, thermodynamics

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2399 Autophagy Regulates Human Hepatocellular Carcinoma Tumorigenesis through Selective Degradation of Cyclin D1

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

Abstract:

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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