Search results for: transdermal drug delivery

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

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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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Authors: O. F. Elkommos

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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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Authors: Lorho Mary Maheo, Arundhati Maibam Devi

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

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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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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: Pankhuri Dagaonkar, Charumani Singh, Poornima Krothapalli, Krishna Karthik

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The backbone of any retail e-commerce success story is a unique design of supply chain network, providing the business an unparalleled speed and scalability. Primary goal of the supply chain strategy is to meet customer expectation by offering fastest deliveries while keeping the cost minimal. Meeting this objective at the large market that India provides is the problem statement that we have targeted here. There are many models and optimization techniques focused on network design to identify the ideal facility location and size, optimizing cost and speed. In this paper we are presenting a tactical approach to optimize cost of an existing network for a predefined speed. We have considered both forward and reverse logistics of a retail e-commerce supply chain consisting of multiple fulfillment (warehouse) and delivery centers, which are connected via sortation nodes. The mathematical model presented here determines if the shipment from a node should get sorted directly for the last mile delivery center or it should travel as consolidated package to another node for further sortation (resort). The objective function minimizes the total cost by varying the resort percentages between nodes and provides the optimal resource allocation and number of sorts at each node.

Keywords: distribution strategy, mathematical model, network design, supply chain management

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Authors: Amin Karimi, Lele Zhang, Mark Fackrell

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Rural-to-urban population migrations are a global phenomenon, with projections indicating that by 2050, 68% of the world's population will inhabit densely populated urban centers. Concurrently, the popularity of e-commerce shopping has surged, evidenced by a 51% increase in total e-commerce sales from 2017 to 2021. Consequently, distribution and logistics systems, integral to effective supply chain management, confront escalating hurdles in efficiently delivering and distributing products within bustling urban environments. Additionally, events like environmental challenges and the COVID-19 pandemic have indicated that decision-makers are facing numerous sources of uncertainty. Therefore, to design an efficient and reliable logistics system, uncertainty must be considered. In this study, it examine fleet sizing and routing while considering uncertainty in demand rate. Fleet sizing is typically a strategic-level decision, while routing is an operational-level one. In this study, a carrier must make two types of decisions: strategic-level decisions regarding the number and types of drones to be purchased, and operational-level decisions regarding planning routes based on available fleet and realized demand. If the available fleets are insufficient to serve some customers, the carrier must outsource that delivery at a relatively high cost, calculated per order. With this hierarchy of decisions, it can model the problem using two-stage stochastic programming. The first-stage decisions involve planning the number and type of drones to be purchased, while the second-stage decisions involve planning routes. To solve this model, it employ logic-based benders decomposition, which decomposes the problem into a master problem and a set of sub-problems. The master problem becomes a mixed integer programming model to find the best fleet sizing decisions, and the sub-problems become capacitated vehicle routing problems considering battery status. Additionally, it assume a heterogeneous fleet based on load and battery capacity, and it consider that battery health deteriorates over time as it plan for multiple periods.

Keywords: drone-delivery, stochastic demand, VRP, fleet sizing

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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: 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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Authors: Abisha Isaac Mohanlal

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Amidst all suspicions and cynicism raised by the legal fraternity, Artificial Intelligence has found its way into the legal system and has revolutionized the conventional forms of legal services delivery. Be it legal argumentation and research or resolution of complex legal disputes; artificial intelligence has crept into all legs of modern day legal services. Its impact has been largely felt by way of big data, legal expert systems, prediction tools, e-lawyering, automated mediation, etc., and lawyers around the world are forced to upgrade themselves and their firms to stay in line with the growth of technology in law. Researchers predict that the future of legal services would belong to artificial intelligence and that the age of human lawyers will soon rust. But as far as the Judiciary is concerned, even in the developed countries, the system has not fully drifted away from the orthodoxy of preferring Natural Intelligence over Artificial Intelligence. Since Judicial decision-making involves a lot of unstructured and rather unprecedented situations which have no single correct answer, and looming questions of legal interpretation arise in most of the cases, discretion and Emotional Intelligence play an unavoidable role. Added to that, there are several ethical, moral and policy issues to be confronted before permitting the intrusion of Artificial Intelligence into the judicial system. As of today, the human judge is the unrivalled master of most of the judicial systems around the globe. Yet, scientists of Artificial Intelligence claim that robot judges can replace human judges irrespective of how daunting the complexity of issues is and how sophisticated the cognitive competence required is. They go on to contend that even if the system is too rigid to allow robot judges to substitute human judges in the recent future, Artificial Intelligence may still aid in other judicial tasks such as drafting judicial documents, intelligent document assembly, case retrieval, etc., and also promote overall flexibility, efficiency, and accuracy in the disposal of cases. By deconstructing the major challenges that Artificial Intelligence has to overcome in order to successfully invade the human- dominated judicial sphere, and critically evaluating the potential differences it would make in the system of justice delivery, the author tries to argue that penetration of Artificial Intelligence into the Judiciary could surely be enhancive and reparative, if not fully transformative.

Keywords: artificial intelligence, judicial decision making, judicial systems, legal services delivery

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Authors: Maryam S. Ghoraishi, John E. Hawk, Thomas Thundat

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Understanding liquid properties in small scale has become important in recent decades as immerging new microelectromechanical systems (MEMS) devices have been widely used for micro pumps, drug delivery, and many other laboratory-on-microchips analysis. Often in microfluidic devices, fluids are transported electrokinetically. Therefore, extensive knowledge of fluid flow, heat transport, electrokinetics and electrochemistry are key to successful lab on a chip design. Among different microfluidic devices, recently developed hollow channel cantilever offers an ideal platform to study different fluid properties simultaneously without drastic decrease in quality factor which normally occurs when traditional cantilevers operate in the liquid phase. Using hollow channel cantilever, we monitor changes in density and viscosity of liquid while simultaneously investigating dielectric properties of alcohol water binary mixtures. Considerable research has been conducted on alcohol-water mixtures since such a mixture is a typical prototype for biomolecules, Micelle formation, and structural stability of proteins (to name a few). Here we show that hollow channel cantilever can be employed to investigate dielectric properties of ethanol/water mixtures in different concentrations. We study dynamic amplitude shifts of hollow channel cantilever oscillation at different concentrations of ethanol/water for different voltages. Our results show how interactions between solute and solvent, and possibly cluster formation, could change dielectric properties and dipole reorientation of the mixture, as well as the resulting force on the hollow cantilever. For comparison, we also examine higher conductivity ionic mixtures of sodium sulfate solution under the same conditions as low conductivity ethanol/water mixtures. We will show the results from systematic investigation of solvent effects on dielectric properties of the binary mixture. We will also address the question of resolution limits in dielectric study of analyte molecules imposed by solvent concentrations.

Keywords: dielectric constant, cantilever sensors, ethanol water mixtures, low frequency

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Authors: R. H. Bustos, L. Martinez, J. García, F. Suárez

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MRP1 (Multi-drug resistance associated protein 1) and MRP2 (Multi-drug resistance associated protein 2) are two proteins belonging to the transporters of ABC (ATP-Binding Cassette). These transporter proteins are involved in the efflux of several biological drugs and xenobiotic and also in multiple physiological, pathological and pharmacological processes. Evidence has been found that there is a correlation among different polymorphisms found and their clinical implication in the resistance to antiepileptic, chemotherapy and anti-infectious drugs. In our study, exonic regions of MRP1/ABCC1 y MRP2/ABCC2 were studied in the Colombian population, specifically in the region of the central Savannah (Cundinamarca) to determinate SNP (Single Nucleotide Polymorphisms) and determinate its allele frequency and its genomics frequency. Results showed that for our population, SNP are found that have been previously reported for MRP1/ABCC1 (rs200647436, rs200624910, rs150214567) as well as for MRP2/ABCC2 (rs2273697, rs3740066, rs142573385, rs17216212). In addition, 13 new SNP were identified. Evidences show an important clinic correlation for polymorphisms rs3740066 and rs2273697. The study object population displays genetic variability as compared to the one reported in other populations.

Keywords: ATP-binding cassette (ABCC), Colombian population, multidrug-resistance protein (MRP), pharmacogenetic, single nucleotide polymorphism (SNP)

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Authors: Angela Knox

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Student diversity in postgraduate classes puts major challengesoneducatorsseekingtoencouragestudentengagementand desired learning outcomes. This paper outlines the impact of a set of teaching initiatives aimed at addressing challenges associated with teaching and learning in an environment characterized by diversity in the student cohort. The study examines postgraduate students completing the core capstone unit within a specialized business degree. Although relatively small, the student cohort is highly diverse in terms of cultural backgrounds represented, prior learning and/or qualifications,aswellasdurationandtypeofworkexperiencerelevant to the degree being completed. The wide range of cultures, existing knowledge, and experience create enormous challenges with respect to students’ learning needs and outcomes. Subsequently, a suite of teaching innovations has been adopted to enhance curriculum content/delivery and the design of assessments. This paperexplores the impact of formalized group charters on students’ learning outcomes. Data from surveys and focus groups are used to assess the effectiveness of these practices. The results highlight the effectiveness of formalizedgroup charters in addressing diverse student needs and enhancing student engagement and learning outcomes. Thesefindings suggest that such practices would benefit students’ learning in environments marked by diversity in the student cohort. Specific recommendationsareofferedforothereducatorsworkingwithdiverse classes.

Keywords: assessment design, curriculum content, curriculum delivery, group charter, student diversity

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Authors: Ishani Das, Avinash Padhi, Sitabja Mukherjee, Santosh Kar, Avinash Sonawane

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Activation of cell mediated and humoral immune responses to Mycobacterium tuberculosis (Mtb) are critical for protection. Herein, we show that mice immunized with Mtb lipid bound chitosan nanoparticles(NPs) induce secretion of prominent Th1 and Th2 cytokines in lymph node and spleen cells, and also induced significantly higher levels of IgG, IgG1, IgG2 and IgM in comparison to control mice measured by ELISA. Furthermore, significantly enhanced γδ-T cell activation was observed in lymph node cells isolated from mice immunized with Mtb lipid coated chitosan-NPs as compared to mice immunized with chitosan-NPs alone or Mtb lipid liposomes through flow cytometric analysis. Also, it was observed that in comparison to CD8+ cells, significantly higher CD4+ cells were present in both the lymph node and spleen cells isolated from mice immunized with Mtb lipid coated chitosan NP. In conclusion, this study represents a promising new strategy for efficient delivery of Mtb lipids using chitosan NPs to trigger enhanced cell mediated and antibody response against Mtb lipids.

Keywords: antibody response, chitosan nanoparticles, cytokines, mycobacterium tuberculosis lipids

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Authors: Veronika Sharok

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Research relevance on psychological determinants of risky behaviors is caused by high prevalence of such behaviors, particularly among youth. Risky sexual behavior, including unprotected and casual sex, frequent change of sexual partners, drug and alcohol use lead to negative social consequences and contribute to the spread of HIV infection and other sexually transmitted diseases. Data were obtained from 302 respondents aged 15-35 which were divided into 3 empirical groups: persons prone to risky sexual behavior, drug users and alcohol users; and 3 control groups: the individuals who are not prone to risky sexual behavior, persons who do not use drugs and the respondents who do not use alcohol. For processing, we used the following methods: Qualitative method for nominative data (Chi-squared test) and quantitative methods for metric data (student's t-test, Fisher's F-test, Pearson's r correlation test). Statistical processing was performed using Statistica 6.0 software. The study identifies two groups of factors that prevent risky behaviors. Internal factors, which include the moral and value attitudes; significance of existential values: love, life, self-actualization and search for the meaning of life; understanding independence as a responsibility for the freedom and ability to get attached to someone or something up to a point when this relationship starts restricting the freedom and becomes vital; awareness of risky behaviors as dangerous for the person and for others; self-acknowledgement. External factors (prevent risky behaviors in case of absence of the internal ones): absence of risky behaviors among friends and relatives; socio-demographic characteristics (middle class, marital status); awareness about the negative consequences of risky behaviors; inaccessibility to psychoactive substances. These factors are common for proneness to each type of risky behavior, because it usually caused by the same reasons. It should be noted that if prevention of risky behavior is based only on elimination of external factors, it is not as effective as it may be if we pay more attention to internal factors. The results obtained in the study can be used to develop training programs and activities for prevention of risky behaviors, for using values preventing such behaviors and promoting healthy lifestyle.

Keywords: existential values, prevention, psychological features, risky behavior

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Authors: Funmilayo Abiola Opadoja, Samuel Olukayode Awotona

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Nursing services costing has been a major interest to nurses for a long period of time. Determination of nursing costing is germane in order to show the effectiveness of nursing practice in an improved and affordable health care delivery system. This has been a major concern of managers that have the mind of quality and affordable health services. The treatment or intervention should be considered as ‘product’ of nursing care and should provide an explainable term for billing. The study was non-experimental, descriptive and went about eliciting the views of nurses on costing nursing care at two public hospitals namely: University College Hospital and Adeoyo Maternity Teaching Hospital. The questionnaire was the instrument used in eliciting nurse’s response. It was administered randomly on 300 selected respondents across various wards within the hospitals. The data was collected and analysed using SPSS20.0 to generate frequency, and cross-tabulations to explore the statistical relationship between variables. The result shows that 89.2% of the respondents viewed costing of nursing care as an important issued to be looked into. The study concluded that nursing care costing is germane to enhancing the status and imagery of the nurses, it is essential because it would enhance the performance of nurses in discharging their duties. There is need to have a procedural manual agreed on by nursing practitioner on costing of each care given.

Keywords: costing, health care delivery system, intervention, nursing care, practitioner

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Authors: Emad Heydarnia, Aref Sepasi, Nika Asefi, Sara Khakshournia, Javad Mohammadnejad

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Background: Despite breakthrough therapeutics in breast cancer, it is one of the main causes of mortality among women worldwide. Thus, drug therapies for treating breast cancer have recently been developed by scientists. Metformin and Sorafenib are well-known therapeutic in breast cancer. In the present study, we combined Sorafenib and PCL-sorafenib with metformin to improve drug absorption and promote therapeutic efficiency. Methods: The MCF-7 cells were treated with Metformin, Sorafenib, or PCL-sorafenib. The growth inhibitory effect of these drugs and cell viability were assessed using MTT and flow cytometry assays, respectively. The expression of targeted genes involved in cell proliferation, signaling, and the cell cycle was measured by Real-time PCR. Results: The results showed that MCF-7 cells treated with Metformin/Sorafenib and PCL-sorafenib/Metformin co-treatment contributed to 50% viability compared to untreated group. Moreover, PI and Annexin V staining tests showed that the cells viability for Metformin/Sorafenib and PCL-sorafenib/Metformin was 38% and 17%, respectively. Furthermore, Sorafenib/Metformin and PCL-sorafenib/Metformin leads to p53 gene expression increase by which they can increase ROS, thereby decreasing GPX4 gene expression. In addition, they affected the expression of BCL2, and BAX genes and altered the cell cycle. Conclusion: Together, the combination of PCL-sorafenib/Metformin and Sorafenib/Metformin increased Sorafenib absorption at lower doses and also leads to apoptosis and oxidative stress increases in MCF-7 cells.

Keywords: breast cancer, metformin, nanotechnology, sorafenib

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Authors: Kai-Cheng Hsu, Tzu-Ying Sung, Jinn-Moon Yang

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Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Although several drugs have been developed to treat colorectal cancer, such as Regorafenib and 5-FU, their efficacy is often limited by the development of drug resistance. Therefore, development of new drugs with new scaffolds is necessary to treat CRC. Here, we used site-moiety maps to identify inhibitors against PIM1, LIMK1, SRC, and mTOR, which are often overexpressed in CRC. A site-moiety map represents physicochemical properties and moiety preferences of a binding site through anchors. An anchor contains three elements: (1) conserved interacting residues of a binding pocket; (2) moiety preference of the binding pocket; and (3) the type (e.g., hydrogen-bonding or van der Waals interactions) of interaction between the moieties and the binding pocket. Then, we performed a structure-based virtual screening of ~260,000 compounds and selected compound candidates with high site-moiety map scores for bioassays. Among these candidates, compound 1 and compound 2 inhibited the growth of CRC cells with IC50 values of <10 μM. The experimental result of enzyme-based assays indicated that compound 1 is a dual inhibitor against PIM1 (IC50 6 μM) and LIMK1(IC50 11 μM). Compound 2 was predicted as a SRC inhibitor and will be further validated. The compounds inhibited different protein targets compared to the current drugs. We believe that the compounds provide a starting point to design new drugs for CRC treatment.

Keywords: colorectal cancer, drug discovery, site-moiety map, virtual screening, PIM1, LIMK1

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Authors: Rachna Jain, Sushila Madan, Bindu Garg

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Cloud computing is the key powerhouse in numerous organizations due to shifting of their data to the cloud environment. In recent years it has been observed that cloud-based-services are being used on large scale for content storage, distribution and processing. Various issues have been observed in cloud computing environment that need to be addressed. Security and privacy are found topmost concern area. In this paper, a novel security model is proposed to secure data by utilizing CDN services like image to icon conversion. CDN Service is a content delivery service which converts an image to icon, word to pdf & Latex to pdf etc. Presented model is used to convert an image into icon by keeping image secret. Here security of image is imparted so that image should be encrypted and decrypted by data owners only. It is also discussed in the paper that how server performs multiplication and selection on encrypted data without decryption. The data can be image file, word file, audio or video file. Moreover, the proposed model is capable enough to multiply images, encrypt them and send to a server application for conversion. Eventually, the prime objective is to encrypt an image and convert the encrypted image to image Icon by utilizing homomorphic encryption.

Keywords: cloud computing, user data security, homomorphic encryption, image multiplication, CDN service

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Authors: K. R. Thabethe, G. A. Adefolaju, M. J. Hosie

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Cervical cancer is the third most commonly diagnosed cancer globally and it is one of three AIDS defining malignancies. Highly active antiretroviral therapy (HAART) is a combination of three or more antiretroviral drugs and has been shown to play a significant role in reducing the incidence of some AIDS defining malignancies, although its effect on cervical cancer is still unclear. The aim of this study was to investigate the relationship between cervical cancer and HAART. This was achieved by studying the expression of two signalling molecules expressed in cervical cancer; MUC1 and P65. Following the 24 hour treatment of a cervical cancer cell line, HCS-2, with drugs which are commonly used as part of HAART at their clinical plasma concentrations, real-time qPCR and immunofluorescence were used in order to study gene and protein expression. A one way ANOVA followed by a Tukey Kramer Post Hoc test was conducted using JMP 11 software on both sets of data. The drug classified as a protease inhibitor (PI) (i.e. LPV/r) reduced MUC1 and P65 gene and protein expression more than the other drug tested. PIs are known to play a significant role in cell death, therefore the cells were thought to be more susceptible to cell death following treatment with PIs. In conclusion, the drugs used, especially the PI showed some anticancer effects by facilitating cell death through decreased gene and protein expression of MUC1 and P65 and present promising agents for cancer treatment.

Keywords: cervical cancer, haart, MUC1, P65

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Authors: Vichayada Laohapiboolkul

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Introduction: As the legal use of cannabis is being widely accepted throughout the world, medical cannabis has been explored in order to become an alternative cure for patients. Tetrahydrocannabinol (THC) and Cannabidiol (CBD) are natural cannabinoids found in the Cannabis plant which is proved to have positive treatment for various diseases and symptoms such as chronic pain, neuropathic pain, spasticity resulting from multiple sclerosis, reduce cancer-associated pain, autism spectrum disorders (ASD), dementia, cannabis and opioid dependence, psychoses/schizophrenia, general social anxiety, posttraumatic stress disorder, anorexia nervosa, attention-deficit hyperactivity disorder, and Tourette's disorder. Regardless of all the medical benefits, THC, if not metabolized, can lead to mild up to severe adverse drug reactions (ADR). The enzyme CYP2C19 was found to be one of the metabolizers of THC. However, the suballele CYP2C19*2 manifests as a poor metabolizer which could lead to higher levels of THC than usual, possibly leading to various ADRs. Objective: The aim of this study was to investigate the distribution of CYP2C19, specifically CYP2C19*2, genes in Thai patients treated with medical cannabis along with adverse drug reactions. Materials and Methods: Clinical data and EDTA whole blood for DNA extraction and genotyping were collected from patients for this study. CYP2C19*2 (681G>A, rs4244285) genotyping was conducted using the Real-time PCR (ABI, Foster City, CA, USA). Results: There were 42 medical cannabis-induced ADRs cases and 18 medical cannabis tolerance controls who were included in this study. A total of 60 patients were observed where 38 (63.3%) patients were female and 22 (36.7%) were male, with a range of age approximately 19 - 87 years. The most apparent ADRs for medical cannabis treatment were dry mouth/dry throat (76.7%), followed by tachycardia (70%), nausea (30%) and a few arrhythmias (10%). In the total of 27 cases, we found a frequency of 18 CYP2C19*1/*1 alleles (normal metabolizers, 66.7%), 8 CYP2C19*1/*2 alleles (intermediate metabolizers, 29.6%) and 1 CYP2C19*2/*2 alleles (poor metabolizers, 3.7%). Meanwhile, 63.6% of CYP2C19*1/*1, 36.3% and 0% of CYP2C19*1/*2 and *2/*2 in the tolerance controls group, respectively. Conclusions: This is the first study to confirm the distribution of CYP2C19*2 allele and the prevalence of poor metabolizer genes in Thai patients who received medical cannabis for treatment. Thus, CYP2C19 allele might serve as a pharmacogenetics marker for screening before initiating treatment.

Keywords: medical cannabis, adverse drug reactions, CYP2C19, tetrahydrocannabinol, poor metabolizer

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Authors: R. Setino, I. M. Ambe, J. A Badenhorst-Weiss

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The South African government supply chain management system is not adequately implemented in State Owned Enterprises (SOEs). There are weaknesses in the SOEs SCM enablers, strategies and policies. In addition, top management of SOEs still do not see SCM as strategic enough to deserve their attention, and therefore, there is very little support from top management, thus making it even difficult for SCM practitioners to execute their day to day functions, let alone delivering the letter and spirit of the relevant legislations. Supply chain strategies lack buy in from the top, and as a result senior SCM practitioners has not been involved in the corporate strategy. This has resulted in supply chain and corporate strategies being misaligned. Due to service delivery backlog, high level of corruption and continuous strikes across the country for better services it is inevitable that government leaders be more strategic about how South Africa can use SCM as a tool to improve service delivery. Consequently, there is a need to close the gap between the strategic level dealt by top management and the application of operational SCM concepts: the use of SCM concepts and, therefore, supply chain strategies – should be aligned with the corporate and business strategies in order to ensure the achievement of top level business objectives. This paper aims to explore supply chain practices in State Owned Enterprises (SOEs). The paper based on a conceptual review provides the status, trends and development and suggests a framework for aligning supply chain strategies and organizational strategies in an SOE environment.

Keywords: alignment, strategies, state owned enterprises, supply chain management, South Africa

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Authors: Tia Kristian Tajnšek, Matjaž Mazaj, Nataša Zabukovec Logar

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Metal-organic frameworks (MOFs) with their specific properties and the possibility of tuning the structure represent excellent candidates for use in the biomedical field. Their advantage lies in large pore surfaces and volumes, as well as the possibility of using bio-friendly or bioactive constituents. So-called bioMOFs are representatives of MOFs, which are constructed from at least one biomolecule (metal, a small bioactive molecule in metal clusters and/or linker) and are intended for bio-application (usually in the field of medicine; most commonly drug delivery). When designing a bioMOF for biomedical applications, we should adhere to some guidelines for an improved toxicological profile of the material. Such as (i) choosing an endogenous/nontoxic metal, (ii) GRAS (generally recognized as safe) linker, and (iii) nontoxic solvents. Design and synthesis of bioNICS-1 (bioMOF of National Institute of Chemistry Slovenia – 1) consider all these guidelines. Zinc (Zn) was chosen as an endogenous metal with an agreeable recommended daily intake (RDI) and LD50 value, and ascorbic acid (Vitamin C) was chosen as a GRAS and active linker. With these building blocks, we have synthesized a bioNICS-1 material. The synthesis was done in ethanol using a solvothermal method. The synthesis protocol was further optimized in three separate ways. Optimization of (i) synthesis parameters to improve the yield of the synthesis, (ii) input reactant ratio and addition of specific modulators for production of larger crystals, and (iii) differing of the heating source (conventional, microwave and ultrasound) to produce nano-crystals. With optimization strategies, the synthesis yield was increased. Larger crystals were prepared for structural analysis with the use of a proper species and amount of modulator. Synthesis protocol was adjusted to different heating sources, resulting in the production of nano-crystals of bioNICS-1 material. BioNICS-1 was further activated in ethanol and structurally characterized, resolving the crystal structure of new material.

Keywords: ascorbic acid, bioMOF, MOF, optimization, synthesis, zinc ascorbate

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Authors: S. Roy, R. Rekha, K. Sriram, G. Subhadra, R. Johana

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Cardiovascular disease remains a leading cause of death in most industrialized countries. Many chemical drugs are available in the market which targets different receptor proteins related to cardiovascular diseases. Of late the traditional herbal drugs are safer when compared to chemical drugs because of its side effects. However, many herbal remedies used in treating cardiovascular diseases have not undergone scientific assessment to prove its pharmacological activities. There are many natural compounds, nature derived and Natural product mimic compounds are available which are in the market as approved drug. In the most of the cases drug activity at the molecular level are not known. Here we have categorized those compounds with our experimental compounds in different classes based on the structural similarity and physicochemical properties, using a tool, Chemmine and has attempted to understand the mechanism of the action of a experimental compound, which are clustered with Simvastatin, Lovastatin, Mevastatin and Pravastatin. Target protein molecule for Simvastatin, Lovastatin, Mevastatin and Pravastatin is HMG-CoA reductase, so we concluded that the experimental compound may be able to bind to the same target. Molecular docking and atomic interaction studies with simvastatin and our experimental compound were compared. A pharmacophore modeling was done based on the experimental compound and HMG-CoA reductase inhibitor.

Keywords: molecular docking, physicochemical properties, pharmacophore modeling structural similarity, pravastatin

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Authors: Eudes Vera

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In this paper, a theoretical evaluation is carried out of the performance of a forthcoming fuel-less clean energy generation device, the Air Motor. The underlying physical principles that support this technology are succinctly described. Examples of the machine and theoretical values of input and output powers are also given. In addition, its main features like portability, on-site energy generation and delivery, miniaturization of generation plants, efficiency, and scaling down of the whole electric infrastructure are discussed. The main component of the Air Motor, the Thermal Air Turbine, generates useful power by converting in mechanical energy part of the thermal energy contained in a fan-produced airflow while leaving intact its kinetic energy. Due to this fact an air motor can contain a long succession of identical air turbines and the total power generated out of a single airflow can be very large, as well as its mechanical efficiency. It is found using the corresponding formulae that the mechanical efficiency of this device can be much greater than 100%, while its thermal efficiency is always less than 100%. On account of its multiple advantages, the Air Motor seems to be the perfect device to convert energy consumers into energy producers worldwide. If so, it would appear that current national electrical grids would no longer be necessary, because it does not seem practical or economical to bring the energy from far-away distances while it can be generated and consumed locally at the consumer’s premises using just the thermal energy contained in the ambient air.

Keywords: electrical grid, clean energy, renewable energy, in situ generation and delivery, generation efficiency

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Authors: Monalisa Pal, Kalyan Mandal

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Herein we report the molecular functionalization of promising transition metal oxide nanostructures, such as Co3O4 nanocubes, using nontoxic and biocompati-ble organic ligand sodium tartrate. The electronic structural modification of the nanocubes imparted through functionalization and subsequent water solubilization reveals multiple absorption bands in the UV-vis region. Further surface modification of the solubilized nanocubes, leads to the emergence of intrinsic multi-color fluorescence (from blue, cyan, green to red region of the spectrum), upon excitation at proper wavelengths, where the respective excitation wavelengths have a direct correlation with the observed UV-vis absorption bands. Using a multitude of spectroscopic tools we have investigated the mechanistic insight behind the origin of different UV-vis absorption bands and emergence of multicolor photoluminescence from the functionalized nanocubes. Our detailed study shows that ligand to metal charge transfer (LMCT) from tartrate ligand to Co2+/Co3+ ions and d-d transitions involving Co2+/Co3+ ions are responsible for generation of this novel optical properties. Magnetic study reveals that, antiferromagnetic nature of Co3O4 nanocubes changes to ferromagnetic behavior upon functionalization, however, the overall magnetic response was very weak. To combine strong magnetism with this novel optical property, we followed the same surface modification strategy in case of CoFe2O4 nanoparticles, which reveals that irrespective of size and shape, all Co-based oxides can develop intrinsic multi-color fluorescence upon facile functionalization with sodium tartrate ligands and the magnetic response was significantly higher. Surface modified Co-based oxide nanostructures also show excellent catalytic activity in degradation of biologically and environmentally harmful dyes. We hope that, our developed facile functionalization strategy of Co-based oxides will open up new opportunities in the field of biomedical applications such as bio-imaging and targeted drug delivery.

Keywords: co-based oxide nanostructures, functionalization, multi-color fluorescence, catalysis

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Authors: S. Yeo, M. Mathur

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Introduction: Obesity, defined as a Body Mass Index (BMI) of more than or equal to 30kg/m, is associated with an increased risk of complications during pregnancy and delivery. During labour, obese mothers often require greater intervention and have higher rates of caesarean section. Despite a low overall rate of serious complications following caesarean section, a high BMI predisposes to a higher risk of postoperative complications. Our study, therefore, aimed to investigate the impact of antenatal obesity on adverse outcomes following caesarean section, particularly wound-related infections. Materials and Methods: A retrospective cohort study of all caesarean deliveries during the first quarter of a chosen year was undertaken in our hospital, which is a tertiary referral centre with > 12,000 deliveries per year. Patients’ health records and data from our hospital’s electronic labour and delivery database were reviewed. Data analysis was performed using the Statistical Package for the Social Sciences (SPSS), and odds ratios plus adjusted odd ratios were calculated with 95% confidence intervals (CI). Results: A total of 1829 deliveries were reviewed during our study period. Of these, 180 (9.8%) patients were obese. The rate of caesarean delivery was 48.9% in obese patients versus 28.1% in non-obese patients. Post-operatively, 17% of obese patients experienced wound infection versus 0.2% of non-obese patients. Obese patients were also more likely to experience major postpartum haemorrhage (4.6% vs. 0.2%) and postpartum pyrexia (18.2% vs. 5.0%) in comparison to non-obese patients. Conclusions: Obesity is a significant risk factor in the development of postoperative complications following caesarean section. Wound infection remains a major concern for obese patients undergoing major surgery and results in extensive morbidity during the postnatal period. Postpartum infection can prolong recovery and affect maternal mental health, leading to reduced perinatal bonding with long-term implications on breastfeeding and parenting confidence. This study supports the need for the development of standardized protocols specifically for obese patients undergoing caesarean section. Multidisciplinary team care, in conjunction with anaesthesia, family physicians, and plastic surgery counterparts, early on in the antenatal journey, may be beneficial where wound complications are anticipated and to minimize the burden of postoperative infection in obese mothers.

Keywords: pregnancy, obesity, caesarean, infection

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Authors: Nisa Mohan

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Clinical coding is a feasible method for estimating the national prevalence of adverse drug event (ADE) admissions. However, under-coding of ADE admissions is a limitation of this method. Whilst the under-coding will impact the accurate estimation of the actual burden of ADEs, the feasibility of the coded data in estimating the adverse drug event admissions goes much further compared to the other methods. Therefore, it is necessary to know the reasons for the under-coding in order to improve the clinical coding of ADE admissions. The ability to identify the reasons for the under-coding of ADE admissions rests on understanding the decision-making process of coding ADE admissions. Hence, the current study aimed to explore the decision-making process of clinical coders when coding cases of ADE admissions. Clinical coders from different levels of coding job such as trainee, intermediate and advanced level coders were purposefully selected for the interviews. Thirteen clinical coders were recruited from two Auckland region District Health Board hospitals for the interview study. Semi-structured, one-on-one, face-to-face interviews using open-ended questions were conducted with the selected clinical coders. Interviews were about 20 to 30 minutes long and were audio-recorded with the approval of the participants. The interview data were analysed using a general inductive approach. The interviews with the clinical coders revealed that the coders have targets to meet, and they sometimes hesitate to adhere to the coding standards. Coders deviate from the standard coding processes to make a decision. Coders avoid contacting the doctors for clarifying small doubts such as ADEs and the name of the medications because of the delay in getting a reply from the doctors. They prefer to do some research themselves or take help from their seniors and colleagues for making a decision because they can avoid a long wait to get a reply from the doctors. Coders think of ADE as a small thing. Lack of time for searching for information to confirm an ADE admission, inadequate communication with clinicians, along with coders’ belief that an ADE is a small thing may contribute to the under-coding of the ADE admissions. These findings suggest that further work is needed on interventions to improve the clinical coding of ADE admissions. Providing education to coders about the importance of ADEs, educating clinicians about the importance of clear and confirmed medical records entries, availing pharmacists’ services to improve the detection and clear documentation of ADE admissions, and including a mandatory field in the discharge summary about external causes of diseases may be useful for improving the clinical coding of ADE admissions. The findings of the research will help the policymakers to make informed decisions about the improvements. This study urges the coding policymakers, auditors, and trainers to engage with the unconscious cognitive biases and short-cuts of the clinical coders. This country-specific research conducted in New Zealand may also benefit other countries by providing insight into the clinical coding of ADE admissions and will offer guidance about where to focus changes and improvement initiatives.

Keywords: adverse drug events, clinical coders, decision making, hospital admissions

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