Search results for: drug target

Authors: Raouf Alizadeh, Kadijeh Hemmati

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The aim of this study is to synthesize several series of hydrogels from combination of a natural based polymer (Quince seed mucilage QSD), a synthetic copolymer contained methoxy poly ethylene glycol -polycaprolactone (mPEG-PCL) in the presence of different amount of multi-walled carbon nanotube (f-MWNT). Mono epoxide functionalized mPEG (mP EG-EP) was synthesized and reacted with sodium azide in the presence of NH4Cl to afford mPEG- N3(-OH). Then ring opening polymerization (ROP) of ε–caprolactone (CL) in the presence of mPEG- N3(-OH) as initiator and Sn(Oct)2 as catalyst led to preparation of mPEG-PCL- N3(-OH ) which was grafted onto propagylated f-MWNT by the click reaction to obtain mPEG-PCL- f-MWNT (-OH ). In the presence of mPEG- N3(-Br) and mixture of NHS/DCC/ QSD, hybrid hydrogels were successfully synthesized. The copolymers and hydrogels were characterized using different techniques such as, scanning electron microscope (SEM) and thermogravimetric analysis (TGA). The gel content of hydrogels showed dependence on the weight ratio of QSD:mPEG-PCL:f-MWNT. The swelling behavior of the prepared hydrogels was also studied under variation of pH, immersion time, and temperature. According to the results, the swelling behavior of the prepared hydrogels showed significant dependence in the gel content, pH, immersion time and temperature. The highest swelling was observed at room temperature, in 60 min and at pH 8. The loading and in-vitro release of quercetin as a model drug were investigated at pH of 2.2 and 7.4, and the results showed that release rate at pH 7.4 was faster than that at pH 2.2. The total loading and release showed dependence on the network structure of hydrogels and were in the range of 65- 91%. In addition, the cytotoxicity and release kinetics of the prepared hydrogels were also investigated.

Keywords: antioxidant, drug delivery, Quince Seed Mucilage(QSD), swelling behavior

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Authors: Asma Ansari, Afsheen Aman, Shah Ali Ul Qader

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In the past few years, numerous concerns have been raised against increased bacterial resistance towards effective drugs and become a debated issue all over the world. With the emergence of drug resistant pathogens, the interaction of natural antimicrobial compounds and antibacterial nanoparticles has emerged as a potential candidate for combating infectious diseases. Microbial diversity in the biome provides an opportunity to screen new species which are capable of producing large number of antimicrobial compounds. Among these antimicrobial compounds, bacteriocins are highly specific and efficient antagonists. A combination of bacteriocin along with nanoparticles could prove to be more potent due to broadened antibacterial spectrum with possibly lower doses. In the current study, silver nanoparticles were synthesized through biological reduction using various isolated bacterial, fungal and yeast strains. Spectroscopy and scanning electron microscopy (SEM) was performed for the confirmation of nanoparticles. Bacteriocin was characterized and purified to homogeneity through gel permeation chromatography. The estimated molecular weight of bacteriocin was 10 kDa. Amino acid analysis and N-terminal sequencing revealed the novelty of the protein. Then antibacterial potential of silver nanoparticles and broad inhibitory spectrum bacteriocin was determined through agar well diffusion assay. These synthesized bacteriocin-Nanoparticles exhibit a good potential for clinical applications as compared to bacteriocin alone. This combination of bacteriocin with nanoparticles will be used as a new sort of biocide in the field of nano-proteomics. The advancement of nanoparticles-mediated drug delivery system will open a new age for rapid eradication of pathogens from biological systems.

Keywords: BAC-IB17, multidrug resistance, purification, silver nanoparticles

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Authors: Hyuk Sang Yoo, Young Ju Son, Wei Mao, Myung Gu Kang, Sol Lee

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Biomedical applications of electrospun nanofibrous meshes have been received tremendous attentions because of their unique structures and versatilities as biomaterials. Incorporation of growth factors in fibrous meshes can be performed by surface-modification and encapsulation. Those growth factors stimulate differentiation and proliferation of specific types of cells and thus lead tissue regenerations of specific cell types. Topographical cues of electrospun nanofibrous meshes also increase differentiation of specific cell types according to alignments of fibrous structures. Wound healing treatments of diabetic ulcers were performed using nanofibrous meshes encapsulating multiple growth factors. Aligned nanofibrous meshes and those with random configuration were compared for differentiating mesenchymal stem cells into neuronal cells. Thus, nanofibrous meshes can be applied to drug delivery carriers and matrix for promoting cellular proliferation.

Keywords: nanofiber, tissue, mesh, drug

Procedia PDF Downloads 326

Authors: Josiah Damisa, Michelle Louise Richardson, Morenike Adewuyi

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Lower back pain is a significant cause of disability worldwide and associated with great implications in terms of the well-being of affected individuals and society as a whole due to its undeniable socio-economic impact. With its prevalence on the increase as a result of an aging global population, the need for novel forms of pain management is ever paramount. This review aims to provide further insight into current research regarding a role for the endocannabinoid signaling pathway as a target in the treatment of chronic pain, with particular emphasis on its potential use as part of the treatment of lower back pain. Potential advantages and limitations of cannabis-based medicines over other forms of analgesia currently licensed for medical use are discussed in addition to areas that require ongoing consideration and research. To evaluate the efficacy of cannabis-based medicines in chronic pain, studies pertaining to the role of medical cannabis in chronic disease were reviewed. Standard searches of PubMed, Google Scholar and Web of Science databases were undertaken with peer-reviewed journal articles reviewed based on the indication for pain management, cannabis treatment modality used and study outcomes. Multiple studies suggest an emerging role for cannabis-based medicines as therapeutic agents in the treatment of chronic back pain. A potential synergistic effect has also been purported if these medicines are co-administered with opiate analgesia due to the similarity of the opiate and endocannabinoid signaling pathways. However, whilst recent changes to legislation in the United Kingdom mean that cannabis is now licensed for medicinal use on NHS prescription for a number of chronic health conditions, concerns remain as to the efficacy and safety of cannabis-based medicines. Research is lacking into both their side effect profiles and the long-term effects of cannabis use. Legal and ethical considerations to the use of these products in standardized medical practice also persist due to the notoriety of cannabis as a drug of abuse. Despite this, cannabis is beginning to gain traction as an alternative or even complementary drug to opiates, with some preclinical studies showing opiate-sparing effects. Whilst there is a paucity of clinical trials in this field, there is scope for cannabinoids to be successful anti-nociceptive agents in managing chronic back pain. The ultimate aim would be to utilize cannabis-based medicines as alternative or complementary therapies, thereby reducing opiate over-reliance and providing hope to individuals who have exhausted all other forms of standard treatment.

Keywords: endocannabinoids, cannabis-based medicines, chronic pain, lower back pain

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Authors: Vanlounni Sibounheuang, Wanarat Anusornsangiam, Pattarin Kittiboonyakun, Chanthanom Manithip

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In worldwide, one of the most common use of oral anticoagulant is warfarin. Its margin between therapeutic inhibition of clot formation and bleeding complications is narrow. Mahosot Hospital, warfarin clinic had not been established yet. The descriptive study was conducted by investigating drug-related problems of outpatients using warfarin, the value of the international normalized ratio (INR) higher than normal ranges (25.40 % of the total 272 outpatients) were mostly identified at Lao-Luxembourg Heart Centre, Mahosot Hospital, Lao PDR. This result led to the present study conducting qualitative interviews in order to help establish a warfarin clinic at Mahosot Hospital for the better outcomes of patients using warfarin. The purpose of this study was to explore perspectives of healthcare professional providing services for outpatients using warfarin. The face to face, in-depth interviews were undertaken among nine healthcare professionals (doctor=3, nurse=3, pharmacist=3) working at out-patient clinic, Lao-Luxembourg Heart Centre, Mahosot Hospital, Lao PDR. The interview guides were developed, and they were validated by the experts in the fields of qualitative research. Each interview lasted approximately 20 minutes. Three major themes emerged; healthcare professional’s experiences of current practice problems with warfarin therapy, healthcare professionals’ views of medical problems related to patients using warfarin, and healthcare professionals’ perspectives on ways of service improvement. All healthcare professionals had the same views that it’s difficult to achieve INR goal for individual patients because of some important patient barriers especially lack of knowledge about to use warfarin properly and safety, patients not regularly follow-up due to problems with transportations and financial support. Doctors and nurses agreed to have a pharmacist running a routine warfarin clinic and provided counselling to individual patients on the following points: how to take drug properly and safety, drug-drug and food-drug interactions, common side effects and how to manage them, lifestyle modifications. From the interviews, some important components of the establishment of a warfarin clinic included financial support, increased human resources, improved the system of keeping patients’ medical records, short course training for pharmacists. This study indicated the acceptance of healthcare professionals on the important roles of pharmacists and the feasibility of setting up warfarin clinic by working together with the multidisciplinary health care team in order to help improve health outcomes of patients using warfarin at Mahosot Hospital, Lao PDR.

Keywords: perspectives, healthcare professional, warfarin therapy, Mahosot Hospital

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Authors: Debasish Pradhan, Shaktiprasad Pradhan, Rakesh Kumar Pradhan, Gitanjali Tripathy

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Suppressors of cytokine signalling (SOCS1), a newly indentified antiapoptotic molecule is a downstream effector of the receptor tyrosine kinase-Ras signalling pathway. The current study has uncovered that SOCS1 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. To investigate the impact of SOCS1 on MDR, we analyzed the expression of P-gp and SOCS1 by immunohistochemistry and found there was a positive correlation between them. At that point, we effectively interfered with RNA translation by the contamination of siRNA of SOCS1 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi, the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise, the expression of P53 protein increased in a statistically significant manner (p ≤ 0.01) after RNAi exposure. Moreover, flow cytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. These outcomes proposed SOCS1 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability.

Keywords: breast cancer, multidrug resistance, SOCS1 gene, MDR1 gene, RNA interference

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Authors: Laurent Maurin, Mervi Toivanen

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This paper estimates euro area banks’ internal target capital ratios and investigates whether banks’ adjustment to the targets have an impact on credit supply and holding of securities during the financial crisis in 2005-2011. Using data on listed banks and country-specific macro-variables a partial adjustment model is estimated in a panel context. The results indicate, firstly, that an increase in the riskiness of banks’ balance sheets influences positively on the target capital ratios. Secondly, the adjustment towards higher equilibrium capital ratios has a significant impact on banks’ assets. The impact is found to be more size-able on security holdings than on loans, thereby suggesting a pecking order.

Keywords: Euro area, capital ratios, credit supply, partial adjustment model

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Authors: Samatha Ss Sutton, Kaouther Kooli

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In recent years social media influences (SMI) have become integrated into many companies marketing strategies to create buzz, target new and younger markets and further expand social media coverage in business (Lim et al 2017). SMI’s can be defined as online personalities with a substantial number of followers, across one or more social media platforms, with influence on their followers (Lou and Yuan 2018). Recently expenditure on influencer marketing has increased exponentially becoming an important area for marketing opportunities and strategies in the future (Lou and Yuan 2018). In order to market products and brands effectively through SMI’s it is important for business to understand the attributes of SMI that effect purchase intention (Lim et al 2017) of their followers and whether or not these attributes vary across generations so to market effectively to their specific segment or target market. The present study involves quantitative research to understand the attributes by which influence differs across generations namely Generation X and Millennials and its effects on purchase intentions of these generational groups. A survey will be conducted using an online questionnaire. Structural Equation Modelling and Multi group analysis will be applied. The study provides insight to marketers/decision makers on how to use influencers accordingly with their target consumer.

Keywords: social media marketing, social media influencers, attitude towards social media influencers, intention to purchase

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Authors: Cristian Crespo

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Conditional cash transfers (CCTs) have been targeted towards the poor. Thus, their targeting assessments check whether these schemes have been allocated to low-income households or individuals. However, CCTs have more than one goal and target group. An additional goal of CCTs is to increase school enrolment. Hence, students at risk of dropping out of school also are a target group. This paper analyses whether one of the most common targeting mechanisms of CCTs, a proxy means test (PMT), is suitable to identify the poor and future school dropouts. The PMT is compared with alternative approaches that use the outputs of a predictive model of school dropout. This model was built using machine learning algorithms and rich administrative datasets from Chile. The paper shows that using machine learning outputs in conjunction with the PMT increases targeting effectiveness by identifying more students who are either poor or future dropouts. This joint targeting approach increases effectiveness in different scenarios except when the social valuation of the two target groups largely differs. In these cases, the most likely optimal approach is to solely adopt the targeting mechanism designed to find the highly valued group.

Keywords: conditional cash transfers, machine learning, poverty, proxy means tests, school dropout prediction, targeting

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Authors: Arindam Pramanik, Parimal Karmakar

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We have explored the synergistic anti-cancer activity of copper ion and acetylacetone complex containing 1,3 diketone group (like curcumin) in metallorganic compound “Copper acetylacetonate” (CuAA). The cytotoxicity mechanism of CuAA complex was evaluated on various cancer cell lines in vitro. Among these, reactive oxygen species (ROS), glutathione level (GSH) in the cell was found to increase. Further mitochondrial membrane damage was observed. The fate of cell death was found to be induced by apoptosis. For application purpose, we have developed a novel biodegradable, non-toxic polymer-based nanoparticle which has hydrophobically modified core for loading of the CuAA. Folic acid is conjugated on the surface of the polymer (chitosan) nanoparticle for targeting to cancer cells for minimizing toxicity to normal cells in-vivo. Thus, this novel drug CuAA has an efficient anticancer activity which has been targeted specifically to cancer cells through polymer nanoparticle.

Keywords: anticancer, apoptosis, copper nanoparticle, targeted drug delivery

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Authors: Patompong Satapornpong, Therdpong Tempark, Pawinee Rerknimitr, Jettanong Klaewsongkram, Chonlaphat Sukasem

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Dapsone (4, 4’-diaminodiphenyl sulfone, DDS) is broadly used for the treatment of inflammatory diseases and infections such as; leprosy, Pneumocystis jiroveci pneumonia in patients with HIV infection, neutrophilic dermatoses, dermatitis herpetiformis and autoimmune bullous disease. The severe cutaneous adverse drug reactions (SCARs) including, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) are rare but severe life-threatening adverse drug reactions. Dapsone is one of many culprit drugs induced SJS, TEN and DRESS. Notwithstanding, to our knowledge, there are no studies of the association of HLA class I alleles and dapsone-induced SCARs in non-leprosy Thai patients. This investigation was a prospective cohort study, which performed in a total of 45 non-leprosy patients. Fifteen patients of dapsone-induced SCARs were classified as following the RegiSCAR criteria, and 30 dapsone-tolerant controls were exposed to dapsone more than 6 months without any evidence of cutaneous reactions. The genotyping of HLA-A, -B and –C were performed using sequence-specific oligonucleotides (PCR-SSOs). The Ethics Committee of Ramathibodi hospital, Mahidol University, approved this study. Among all HLA class I alleles, HLA-A*24:07, HLA-B*13:01, HLA-B*15:02, HLA-C*03:04 and HLA-C*03:09 were significantly associated with dapsone-induced SCARs (OR = 10.55, 95% CI = 1.06 – 105.04, p = 0.0360; OR = 56.00, 95% CI = 8.27 – 379.22, p = 0.0001; OR = 7.00, 95% CI = 1.17 – 42.00, p = 0.0322; OR = 6.00, 95% CI = 1.24 – 29.07, p = 0.0425 and OR = 17.08, 95% CI = 0.82 – 355.45, p = 0.0321, respectively). Furthermore, HLA-B*13:01 allele had strong association with dapsone-induced SJS-TEN and DRESS when compared with dapsone-tolerant controls (OR = 42.00, 95% CI = 2.88 – 612.31, p = 0.0064 and OR = 63.00, 95% CI = 7.72 – 513.94 and p = 0.0001, respectively). Consequently, HLA-B*13:01 might serve as a pharmacogenetic marker for screening before initiating the therapy with dapsone for prevention of dapsone-induced SCARs.

Keywords: dapsone-induced SCARs, HLA-B*13:01, HLA class I alleles, severe cutaneous adverse reactions, Thai

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Authors: M. Adamski, J. Cwiklak

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The contemporary battlefield creates a demand for more costly and highly advanced munitions. Training personnel responsible for operations, as well as an immediate execution of combat tasks, which engage real assets, is unrealistic and economically not feasible. Owing to a wide array of exploited simulators and various types of imitators, it is possible to reduce the costs. One of the effective elements of training, which can be applied in the training of all service branches, are imitators of aerial targets. This research serves as an introduction to the commencement of design analysis over a real aerial target imitator. Within the project, the basic aerodynamic calculations were made, which enabled to determine its geometry, design layout, performance, as well as the mass balance of individual components. The conducted calculations of the parameters of flight characteristics come closer to the real performance of such unmanned aerial vehicles.

Keywords: aerial target, aerodynamics, imitator, performance

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Authors: Raquel P. F. Guiné, Daniela V. T. A. Costa, Paula M. R. Correia, Moisés Castro, Luis T. Guerra, Cristina A. Costa

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The aim of this work was to characterize a potential target group of people interested in participating into a training program in organic farming in the context of mobile-learning. The information sought addressed in particular, but not exclusively, possible contents, formats and forms of evaluation that will contribute to define the course objectives and curriculum, as well as to ensure that the course meets the needs of the learners and their preferences. The sample was selected among different European countries. The questionnaires were delivered electronically for answering online and in the end 135 consented valid questionnaires were obtained. The results allowed characterizing the target group and identifying their training needs and preferences towards m-learning formats, giving valuable tools to design the training offer.

Keywords: mobile-learning, organic farming, rural development, survey

Procedia PDF Downloads 487

Authors: Syed Kashif Ali, Usman Javaid, Abdullah Chohan

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In large enterprises multiple departments use different sort of information systems and databases according to their needs. These systems are independent and heterogeneous in nature and sharing information/data between these systems is not an easy task. The usage of middleware technologies have made data sharing between systems very easy. However, monitoring the exchange of data/information for verification purposes between target and source systems is often complex or impossible for maintenance department due to security/access privileges on target and source systems. In this paper, we are intended to present our experience of an end to end data monitoring approach at middle ware level implemented in Oracle BPEL for data verification without any help of monitoring tool.

Keywords: service level agreement, SOA, BPEL, oracle fusion middleware, web service monitoring

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Authors: Ahmed Khalaf Reyad Raslan

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Cancer stem cells (CSCs) describe a class of pluripotent cancer cells that behave analogously to normal stem cells in their ability to differentiate into the spectrum of cell types observed in tumors. The de-differentiation processes, such as an epithelial-mesenchymal transition (EMT), are known to enhance cellular plasticity. Here, we demonstrate a new hypothesis to use hybrid superparamagnetic magnetite nanoparticles (Fe₃O₄)- graphene oxide functionalized surface with Collagen to target the cancer stem cell as an early detection tool for cancer. We think that with the use of magnetic resonance imaging (MRI) and the new hybrid system would be possible to track the cancer stem cells.

Keywords: hydrogel, alginate, reduced graphene oxide, collagen

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Authors: Shuafeng Yuan, Bojian Zheng

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The RNA-dependent RNA polymerase of influenza a virus comprises conserved and independently folded subdomains with defined functionalities. The N-terminal domain of the PA subunit (PAN) harbors the endonuclease function so that it can serve as a desired target for drug discovery. To identify a class of anti-influenza inhibitors that impedes PAN endonuclease activity, a screening approach that integrated the fluorescence resonance energy transfer based endonuclease inhibitor assay with the DNA gel-based endonuclease inhibitor assay was conducted, followed by the evaluation of antiviral efficacies and potential cytotoxicity of the primary hits in vitro and in vivo. A small-molecule compound ANA-0 was identified as a potent inhibitor against the replication of multiple subtypes of influenza A virus, including H1N1, H3N2, H5N1, H7N7, H7N9 and H9N2, in cell cultures. Combinational treatment of zanamivir and ANA-0 exerted synergistic anti-influenza effect in vitro. Intranasal administration of ANA-0 protected mice from lethal challenge and reduced lung viral loads in H1N1 virus infected BALB/c mice. Docking analyses predicted ANA-0 bound the endonuclease cavity of PAN by interacting with the metal-binding and catalytic residues. In summary, ANA-0 shows potential to be developed to novel anti-influenza agents.

Keywords: anti-influenza, novel compound, inhibition of endonuclease, PA

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Authors: P. Tueku, P. Supnithi, R. Wongsathan

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Heat-Assisted Magnetic Recording (HAMR) is one of the leading technologies identified to enable areal density beyond 1 Tb/in2 of magnetic recording systems. A key challenge to HAMR designing is accuracy of positioning, timing of the firing laser, power of the laser, thermo-magnetic head, head-disk interface and cooling system. We study the effect of HAMR parameters on transition center and transition width. The HAMR is model using Thermal Williams-Comstock (TWC) and microtrack model. The target and equalizer are designed by the minimum mean square error (MMSE). The result shows that the unit energy constraint outperforms other constraints.

Keywords: heat-assisted magnetic recording, thermal Williams-Comstock equation, microtrack model, equalizer

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Authors: Hong Zeng

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In the process of popularization of higher education, it is necessary to innovate teaching methods in order to make the students cultivated suitable for the needs of social development. This paper discusses the limitations and shortcomings of the traditional teaching method of teaching approach to a person's aptitude, personality, and interest and introduces the new teaching method of teaching approach to a person's personality. The teaching approach to a person's personality is a target teaching method that aims to develop students' potential and cultivate professional talents. Therefore, teachers should be professional and can adopt modern teaching methods from the Internet so that students can clearly understand the course and the knowledge structure. Finally, the students using new teaching methods can enhance their motivation to study and quickly acquire professional skills.

Keywords: higher education, personality, target education, student-centered

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Authors: Sudhir Kumar, V. R. Sinha

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Water in oil topical microemulsions of 5-FU were developed and optimized using face centered central composite design. Topical w/o microemulsion of 5-FU were prepared using sorbitan monooleate (Span 80), polysorbate 80 (Tween 80), with different oils such as oleic acid (OA), triacetin (TA), and isopropyl myristate (IPM). The ternary phase diagrams designated the microemulsion region and face centered central composite design helped in determining the effects of selected variables viz. type of oil, smix ratio and water concentration on responses like drug content, globule size and viscosity of microemulsions. The CCD design exhibited that the factors have statistically significant effects (p<0.01) on the selected responses. The actual responses showed excellent agreement with the predicted values as suggested by the CCD with lower residual standard error. Similarly, the optimized values were found within the range as predicted by the model. Furthermore, other characteristics of microemulsions like pH, conductivity were investigated. For the optimized microemulsion batch, ex-vivo skin flux, skin irritation and retention studies were performed and compared with marketed 5-FU formulation. In ex vivo skin permeation studies, higher skin retention of drug and minimal flux was achieved for optimized microemulsion batch then the marketed cream. Results confirmed the actual responses to be in agreement with predicted ones with least residual standard errors. Controlled release of drug was achieved for the optimized batch with higher skin retention of 5-FU, which can further be utilized for the treatment of many dermatological disorders.

Keywords: 5-FU, central composite design, microemulsion, ternanry phase diagram

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Authors: Santi Maneewatchararangsri, Wanpen Chaicumpa, Patcharin Saengjaruk, Urai Chaisri

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Leptospirosis is a globally neglected disease that continues to be a significant public health and veterinary burden, with millions of cases reported each year. Early and accurate differential diagnosis of leptospirosis from other febrile illnesses and the development of a broad spectrum of leptospirosis vaccines are needed. The LipL32 outer membrane lipoprotein is a member of Leptospira adhesive matrices and has been found to exert hemolytic activity to erythrocytes in vitro. Therefore, LipL32 is regarded as a potential target for diagnosis, broad-spectrum leptospirosis vaccines, and for passive immunotherapy. In this study, we established LipL32-specific mouse monoclonal antibodies, mAbLPF1 and mAbLPF2, and their respective mouse- and humanized-engineered single chain variable fragment (ScFv). Their antibodies’ neutralizing activities against Leptospira-mediated hemolysis in vitro, and the therapeutic efficacy of mAbs against heterologous Leptospira infected hamsters were demonstrated. The epitope peptide of mAb LPF1 was mapped to a non-contiguous carboxy-terminal β-turn and amphipathic α-helix of LipL32 structure contributing to phospholipid/host cell adhesion and membrane insertion. We found that the mAbLPF2 epitope was located on the interacting loop of peptide binding groove of the LipL32 molecule responsible for interactions with host constituents. Epitope sequences are highly conserved among Leptospira spp. and are absent from the LipL32 superfamily of other microorganisms. Both epitopes are surface-exposed, readily accessible by mAbs, and immunogenic. However, they are less dominant when revealed by LipL32-specific immunoglobulins from leptospirosis-patient sera and rabbit hyperimmune serum raised by whole Leptospira. Our study also demonstrated an adhesion inhibitory activity of LipL32 protein to host membrane components and cells mediated by mAbs as well as an anti-hemolytic activity of the respective antibodies. The therapeutic antibodies, particularly the humanized-ScFv, have a potential for further development as non-drug therapeutic agent for human leptospirosis, especially in subjects allergic to antibiotics. The epitope peptides recognized by two therapeutic mAbs have potential use as tools for structure-function studies. Finally, protective peptides may be used as a target for epitope-based vaccines for control of leptospirosis.

Keywords: leptospira lipl32-specific antibodies, therapeutic epitopes, epitopes characterization, immunotherapy

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Authors: Asher John Mohan, Krishna K. L.

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Objectives: (1) To assess the extent of memory impairment induced by Phenytoin (PHT) at normal and reduced dose on temporal lobe epileptic mice. (2) To evaluate the protective effect of Levetiracetam (LEV) on aggravation of memory impairment in temporal lobe epileptic mice by PHT. Materials and Methods: Albino mice of either sex (n=36) were used for the study for a period of 64 days. Convulsions were induced by intraperitoneal administration of pilocarpine 280 mg/kg on every 6th day. Radial arm maze (RAM) was employed to evaluate the memory impairment activity on every 7th day. The anticonvulsant and memory impairment activity were assessed in PHT normal and reduced doses both alone and in combination with LEV. RAM error scores and convulsive scores were the parameters considered for this study. Brain acetylcholine esterase and glutamate were determined along with histopathological studies of frontal cortex. Results: Administration of PHT for 64 days on mice has shown aggravation of memory impairment activity on temporal lobe epileptic mice. Although the reduction in PHT dose was found to decrease the degree of memory impairment the same decreased the anticonvulsant potency. The combination with LEV not only brought about the correction of impaired memory but also replaced the loss of potency due to the reduction of the dose of the antiepileptic drug employed. These findings were confirmed with enzyme and neurotransmitter levels in addition to histopathological studies. Conclusion: This study thus builds a foundation in combining a nootropic anticonvulsant with an antiepileptic drug to curb the adverse effect of memory impairment associated with temporal lobe epilepsy. However further extensive research is a must for the practical incorporation of this approach into disease therapy.

Keywords: anti-epileptic drug, Phenytoin, memory impairment, Pilocarpine

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Authors: Rawia M. Khalil, Ghada Abd-Elbary, Mona Basha, Ghada E. A. Awad, Hadeer A. Elhashemy

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Background: Bacterial infections of the eye are the clinical conditions responsible for ocular morbidity and blindness. Conjunctivitis is an inflammation of the conjunctiva, due to Staphylococcus aureus. Lomefloxacin HCl (LXN) is a third generation flouroquinolone antibiotic with a broad spectrum against wide range of bacteria and very effective against Staph infections especially in conjunctiva (conjunctivitis). The present study aims to develop and evaluate novel ocular proniosomal gels of Lomefloxacin Hcl (LXN); in order to improve its ocular bioavailability for the management of bacterial conjunctivitis. Materials and methods: Proniosomes were prepared by coacervation phase separation method using different types of nonionic surfactants (Span 60,40,20,Tween 20,40,60,80,Brij 35,98,72) solely and as mixtures with Span® 60. The formed gels were characterized for entrapment efficiency, vesicle size and in vitro drug release. The optimum proniosomal gel; P-LXN 7 were characterized for pH measurement, transmission electron microscopy (TEM) and differential scanning calorimetry (DSC) as well as Stability study and microbiological evaluation .The results revealed that only Span 60 was able to form stable LXN proniosomal gel when used individually while the other nonionic surfactants formed gels only in combination with Span 60 at different ratios. The optimum proniosomal gel; P-LXN 7 (Span60:Tween60, 9:1) appeared as spherical shaped vesicles having high entrapment efficiency (>80 %), appropriate vesicle size (187 nm) as well as controlled drug release over 12h. DSC confirmed the amorphous nature and the uniformity of LXN inclusion within the vesicles. Physical stability study did not show any significant changes in appearance or entrapment efficiency or vesicle size after storage for 3 months at 4°C. Ocular irritancy test revealed that P-LXN 7 was safe, well tolerable and suitable for ocular delivery. In vivo antibacterial activity of P-LXN 7 evaluated using the susceptibility test and topical therapy of induced ocular conjunctivitis confirmed the enhanced antibacterial therapeutic efficacy of the LXN-proniosomal gel compared to the commercially available LXN eye drops; Orchacin®. Conclusions: Our results suggest that proniosomal gels could provide a promising carrier of LXN for efficient ocular treatment of bacterial conjunctivitis.

Keywords: bacterial conjunctivitis, lomefloxacin HCl, ocular drug delivery, proniosomes

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Authors: Selamawit Hirpa, Girmay Medhin, Belaineh Girma, Muluken Melese, Alemayehu Mekonen, Pedro Suarez, Gobena Ameni

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Worldwide, there were 650,000 multi-drug resistant tuberculosis (MDR-TB) cases in 2010. Ethiopia is 15th among the 27 MDR-TB high-burden countries. A case control study was conducted at St. Peter Hospital and five health centers in Addis Ababa. Cases were MDR-TB patients who were in treatment at St. Peter Hospital during the study period. Controls were patients who were on first-line anti-TB treatment and were registered as cured or having completed treatment in the period 9 April 2009– 28 February 2010, in five health centers. A structured interview questionnaire was used to assess factors that could potentially be associated with the occurrence of MDR-TB. Factors that were significantly associated with MDR-TB: drug side effects during first-line treatment (adjusted odds ratio (AOR): 4.5, 95% CI; 1.9 - 10.5); treatment not directly observed by a health worker (AOR = 11.7, 95% CI; 4–34.3); and retreatment with the Category II regimen (P = 0.000).

Keywords: adherence to TB treatment, MDR-TB, TB treatment, TB treatment regimens

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Authors: Sreelekha Prakash, Yulong Gu

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Background: About 61% of adults surveyed across 25 states reported they had experienced at least one type of Adverse Childhood Experience (ACE) before 18 years of age. Relationships between ACEs and a variety of substance-related behaviors and behavioral health have been reported in previous studies. ACEs can have lasting, negative effects on health, well-being, as well as life opportunities such as education and job potential. Objectives: For the current research, the aim was to assess the factors affecting substance use behavior in young adults. The further onset of drug use and its association was analyzed with ACEs and mental health. Method: The young adults from a county in the north-eastern United States were invited to participate in an online questionnaire survey with prior consent through an IRB approved study. The Survey included questions related to social determinants of health, 10 item ACE questionnaire, and substance use related to Alcohol, Marijuana, Opioids, Stimulants, and other drugs. PHQ-9 questionnaire was used to assess cognitive health. Results: Data was analyzed for the 244 completed surveys {68% (165) were females, and 78% (190) were Whites}. The average age of the participants was 26.7 years, and approximately 80% were lifelong residents of the county or year-round residents. Of the respondents, 50% (122) were high school graduates with some college education, and 56% (136) had a full-time jobs. Past 30-day usage for alcohol was 76% (72), and marijuana was 28.4% (27). The data showed that the higher the ACE scores, the younger they start using any substance (p < 0.0001). The data for PHQ-9 and ACE scores showed that the higher the ACE score, the higher the PHQ-9 score, with a significant p-value (p 0.0001). The current data also showed a significant association with other drugs; marijuana use showed significance for 30 days of use (p 0.0001), stimulant use (0.0008), prescription drug misuse (0.01), and opioids (0.01). Conclusion: These findings further support the association between ACEs and initiation of drug use and its correlation with mental health symptoms. Promoting a safe and supportive environment for children and youth in their earlier ages can prevent the youth and young adults from the effects of drug use and create healthy living habits for young adults.

Keywords: subtance use, young adults, adverse childhood experience, PHQ-9

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Authors: M. J. Pourvaghar, Sh. Khoshemehry

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Adopting inappropriate body posture during addiction can cause muscular and skeletal deformities. This study is aimed at investigating the effects of a program of the selected corrective exercises on the kyphosis of addicted male patients. Materials and methods: This was a quasi-experimental study. This study has been carried out using the semi-experimental method. The subjects of the present study included 104 addicted men between 25 to 45 years of age. In 2014, these men were referred to one of the NA (Narcotic Anonymous) centres in Kashan in 2015. A total of 24 people suffering from drug withdrawal, who had abnormal kyphosis, were purposefully selected as a sample. The sample was randomly divided into two groups, experimental and control; each group consisted of 12 people. The experimental group participated in a training program for 12 weeks consisting of three 60 minute sessions per week. That includes strengthening, stretching and PNF exercises (deep stretching of the muscle). The control group did no exercise or corrective activity. The Kolmogorov-Smirnov test was used to assess normal distribution of data; and a paired t-test and covariance analysis test were used to assess the effectiveness of the exercises, with a significance level of P≤0.05 by using SPSS18. The results showed that three months of the selected corrective exercises had a significant effect (P≤ 0.005) on the correction of the kyphosis of the addicted male patients after three months of rehabilitation (drug withdrawal) in the experimental group, while there was no significant difference recorded in the control group (P≥0.05). The results show that exercise and corrective activities can be used as non-invasive and non-pharmacological methods to rehabilitate kyphosis abnormalities after drug withdrawal and treatment for addiction.

Keywords: kyphosis, exercise-rehabilitation, addict, addiction

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Authors: Brian Connett, Bryan O'Halloran

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Systems assets within critical infrastructures were seemingly safe from the exploitation or attack by nefarious cyberspace actors. Now, critical infrastructure is a target and the resources to exploit the cyber physical systems exist. These resources are characterized in terms of patience, stealth, replication-ability and extraordinary robustness. System owners are obligated to maintain a high level of protection measures. The difficulty lies in knowing when to fortify a critical infrastructure against an impending attack. Models currently exist that demonstrate the value of knowing the attacker’s capabilities in the cyber realm and the strength of the target. The shortcomings of these models are that they are not designed to respond to the inherent fast timing of an attack, an impetus that can be derived based on open-source reporting, common knowledge of exploits of and the physical architecture of the infrastructure. A useful model will inform systems owners how to align infrastructure architecture in a manner that is responsive to the capability, willingness and timing of the attacker. This research group has used an existing theoretical model for estimating parameters, and through analysis, to develop a decision tool for would-be target owners. The continuation of the research develops further this model by estimating the variable parameters. Understanding these parameter estimations will uniquely position the decision maker to posture having revealed the vulnerabilities of an attacker’s, persistence and stealth. This research explores different approaches to improve on current attacker-defender models that focus on cyber threats. An existing foundational model takes the point of view of an attacker who must decide what cyber resource to use and when to use it to exploit a system vulnerability. It is valuable for estimating parameters for the model, and through analysis, develop a decision tool for would-be target owners.

Keywords: critical infrastructure, cyber physical systems, modeling, exploitation

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Authors: Larissa Burruano, Sergey Grabovyj, Irina Nguen

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The study aimed to assess the level of adherence to anti retroviral therapy (ART) and to examine the relationship between adherence and risk behavior factor (drug use) among patients infected with HIV. The patients with newly diagnosed or established HIV infection under follow-up at the Sumskij Regional Centre for AIDS Prevention in Ukraine were eligible for this study. Medical records were used to measure the patient’s adherence to medication. Measurements were obtained at month 6 and at month 12 to calculate the number of medication omission during the past 30 days: (on a 2-point scale – once until three in a month – were considered adherent, three and more in a month – were considered non-adherent). Of the 50 study participants, 27 (54.0%) were men and 23 (46.0%) women. The mean age is 35.2 years (SD= 5.1). A majority of the patients (82.0%) is in the age group of 25-30 years. The main level of adherence was 74.0% and 66.0% at 6 and 12 months, respectively. The main routes of HIV transmission were drug injection among men 12 (44.4%) and sexual contact among women 11 (47.8%). Univariate analyses indicated that patients who had lower level of education were more likely to have been non-adherent at month 6- (X2 =5.1, n=50, p < .05) and at month 12 (X2 = 4.34, n=50, p < .05). Multivariate tests showed that only age (OR= 1.163 [95% CI 0.98–1.370]) was significant independent predictor of treatment adherence, while gender, education, employment status were not predictive for the risk of developing non-compliance. There was not a significant interaction between non-adherence and intravenous drug use. Consistent with these findings, younger people were more likely to have missed a dose of their medication because they had a greater sense of invulnerability than older patients. The study indicates that the socio demographic characteristic should be taken into an account in the future research regarding adherence in the case of HIV infection. If the patient anti retroviral adherence can be improved by qualitatively better medical care in all regions of the Ukraine, behavioral changes in the population can to be expected in the long term.

Keywords: HIV, antiretroviral therapy, adherence, Ukraine, Eastern Europe

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Authors: Phenphak Horadee, Rodchares Hanrinth, Saithip Suttiruksa

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Inappropriate use of antibiotics has happened in several hospitals, Thailand. Drug use evaluation (DUE) is one strategy to overcome this difficulty. However, most community hospitals still encounter incomplete evaluation resulting overuse of antibiotics with high cost. Consequently, drug-resistant bacteria have been rising due to inappropriate antibiotic use. The aim of this study was to involve stakeholders in conceptualizing, developing, and prioritizing a feasible intervention strategy to promote and support appropriate antibiotic prescribing in a community hospital, Thailand. Study antibiotics included four antibiotics such as Meropenem, Piperacillin/tazobactam, Amoxicillin/clavulanic acid, and Vancomycin. The study was conducted for the 1-year period between March 1, 2018, and March 31, 2019, in a community hospital in the northeastern part of Thailand. Concept mapping was used in a purposive sample, including doctors (one was an administrator), pharmacists, and nurses who involving drug use evaluation of antibiotics. In-depth interviews for each participant and survey research were conducted to seek the problems for inappropriate use of antibiotics based on drug use evaluation system. Seventy-seven percent of DUE reported appropriate antibiotic prescribing, which still did not reach the goal of 80 percent appropriateness. Meropenem led other antibiotics for inappropriate prescribing. The causes of the unsuccessful DUE program were classified into three themes such as personnel, lack of public relation and communication, and unsupported policy and impractical regulations. During the first meeting, stakeholders (n = 21) expressed the generation of interventions. During the second meeting, participants who were almost the same group of people in the first meeting (n = 21) were requested to independently rate the feasibility and importance of each idea and to categorize them into relevant clusters to facilitate multidimensional scaling and hierarchical cluster analysis. The outputs of analysis included the idealist, cluster list, point map, point rating map, cluster map, and cluster rating map. All of these were distributed to participants (n = 21) during the third meeting to reach consensus on an intervention model. The final proposed intervention strategy included 29 feasible and crucial interventions in seven clusters: development of information technology system, establishing policy and taking it into the action plan, proactive public relations of the policy, action plan and workflow, in cooperation of multidisciplinary teams in drug use evaluation, work review and evaluation with performance reporting, promoting and developing professional and clinical skill for staff with training programs, and developing practical drug use evaluation guideline for antibiotics. These interventions are relevant and fit to several intervention strategies for antibiotic stewardship program in many international organizations such as participation of the multidisciplinary team, developing information technology to support antibiotic smart use, and communication. These interventions were prioritized for implementation over a 1-year period. Once the possibility of each activity or plan is set up, the proposed program could be applied and integrated into hospital policy after evaluating plans. Effectiveness of each intervention could be promoted to other community hospitals to promote and support antibiotic smart use.

Keywords: antibiotic, concept mapping, drug use evaluation, multidisciplinary teams

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Authors: Ignacio Luis Ramirez, Brittney Holcomb

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This study examines attitudes toward sexual assault based on religious affiliation, religiosity, religious beliefs, attitude about sexual assault education, alcohol, and drug use. This study found respondents who identified themselves as Catholics had more negative attitudes toward sexual assault and were more likely to support victim-blaming statements than Baptists or Protestants. Respondents who indicated a greater problem with alcohol had more negative attitudes toward sexual assault and were more likely to support victim-blaming statements. In reference to gender, males had more negative attitudes toward sexual assault and were more likely to support victim-blaming statements than females. The respondent’s religiosity and religious beliefs did not affect their attitudes toward sexual assault. Additionally, attitudes about sexual assault education and drug use did not affect attitudes toward sexual assault.

Keywords: sexual assault, religion, education, alcohol, drugs

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Authors: S. Boulenouar, A. Boukli Hacene, S. Brahmi

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Quality is an old concept but which recently became omnipresent in the society. It is a pledge of the well done job and therefore the satisfaction of the customer. Now, dispensing pharmacies seem to be held away from this approach. Officinal staff is called to dispense drugs. However this essential function is rarely studied and taken into account. To contribute to the good use of medicines and to reduce the dangers, it is important to consider the dispensation of drugs practised in the pharmacies. It is a both descriptive and retrospective study .The descriptive part is to conduct a survey near to the dispensary pharmacists. The retrospective section concentrates on the analysis of medicine prescriptions dispensed to patients. Following the survey that we carried out near the pharmacists of dispensary of the town of Oran, it appears that in majority, they are not inclined, by themselves, to take up the challenge of quality at the dispensary. The approach requires time and a motivation that pharmacists do not have for the moment. Efforts are still needed on the part of pharmacists, but also of authorities and organizations in charge of quality in the dispensary. At the end of this work, it seems to us that the implementation of a quality approach is part of our reflection on the added value of the pharmacist of dispensary in the drug chain.

Keywords: customer satisfaction, dispensary, dispensing of the drug, quality approach

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