Search results for: extensively drug resistant (XDR)-TB
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3495

Search results for: extensively drug resistant (XDR)-TB

2505 Sol-Gel Derived 58S Bioglass Substituted by Li and Mg: A Comparative Evaluation on in vitro Bioactivity, MC3T3 Proliferation and Antibacterial Efficiency

Authors: Amir Khaleghipour, Amirhossein Moghanian, Elhamalsadat Ghaffari

Abstract:

Modified bioactive glass has been considered as a promising multifunctional candidate in bone repair and regeneration due to its attractive properties. The present study mainly aims to evaluate how the individual substitution of lithium (L-BG) and magnesium (M-BG) for calcium can affect the in vitro bioactivity of sol-gel derived substituted 58S bioactive glass (BG); and to present one composition in both of the 60SiO₂–(36-x)CaO–4P₂O₅–(x)Li₂O and 60SiO₂–(36-x)CaO–4P₂O₅–(x)MgO quaternary systems (where x= 0, 5, 10 mol.%) with improved biocompatibility, enhanced alkaline phosphatase (ALP) activity, and the most efficient antibacterial activity against methicillin-resistant Staphylococcus aureus bacteria. To address these aims, and study the effect of CaO/Li₂O and CaO/MgO substitution up to 10 mol % in 58S-BGs, the samples were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, inductively coupled plasma atomic emission spectrometry and scanning electron microscopy after immersion in simulated body fluid up to 14 days. Results indicated that substitution of either CaO/ Li₂O and CaO/ MgO had a retarding effect on in vitro hydroxyapatite (HA) formation due to the lower supersaturation degree for nucleation of HA compared with 58s-BG. Meanwhile, magnesium had a more pronounced effect. The 3-(4, 5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and alkaline phosphatase (ALP) assays showed that both substitutions of CaO/ Li₂O and CaO/ MgO up to 5mol % in 58s-BGs led to increased biocompatibility and stimulated proliferation of the pre-osteoblast MC3T3 cells with respect to the control. On the other hand, substitution of either Li or Mg for Ca in the 58s BG composition resulted in improved bactericidal efficiency against MRSA bacteria. Taken together, sample 58s-BG with 5 mol % CaO/Li₂O substitution (BG-5L) was considered as a multifunctional biomaterial in bone repair/regeneration with improved biocompatibility, enhanced ALP activity as well enhanced antibacterial efficiency against methicillin-resistant Staphylococcus aureus (MRSA) bacteria among all of the synthesized L-BGs and M-BGs.

Keywords: alkaline, alkaline earth, bioactivity, biomedical applications, sol-gel processes

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2504 Proteomic Evaluation of Sex Differences in the Plasma of Non-human Primates Exposed to Ionizing Radiation for Biomarker Discovery

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

Abstract:

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

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

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2503 Performance Evaluation of the CSAN Pronto Point-of-Care Whole Blood Analyzer for Regular Hematological Monitoring During Clozapine Treatment

Authors: Farzana Esmailkassam, Usakorn Kunanuvat, Zahraa Mohammed Ali

Abstract:

Objective: The key barrier in Clozapine treatment of treatment-resistant schizophrenia (TRS) includes frequent bloods draws to monitor neutropenia, the main drug side effect. WBC and ANC monitoring must occur throughout treatment. Accurate WBC and ANC counts are necessary for clinical decisions to halt, modify or continue clozapine treatment. The CSAN Pronto point-of-care (POC) analyzer generates white blood cells (WBC) and absolute neutrophils (ANC) through image analysis of capillary blood. POC monitoring offers significant advantages over central laboratory testing. This study evaluated the performance of the CSAN Pronto against the Beckman DxH900 Hematology laboratory analyzer. Methods: Forty venous samples (EDTA whole blood) with varying concentrations of WBC and ANC as established on the DxH900 analyzer were tested in duplicates on three CSAN Pronto analyzers. Additionally, both venous and capillary samples were concomitantly collected from 20 volunteers and assessed on the CSAN Pronto and the DxH900 analyzer. The analytical performance including precision using liquid quality controls (QCs) as well as patient samples near the medical decision points, and linearity using a mix of high and low patient samples to create five concentrations was also evaluated. Results: In the precision study for QCs and whole blood, WBC and ANC showed CV inside the limits established according to manufacturer and laboratory acceptability standards. WBC and ANC were found to be linear across the measurement range with a correlation of 0.99. WBC and ANC from all analyzers correlated well in venous samples on the DxH900 across the tested sample ranges with a correlation of > 0.95. Mean bias in ANC obtained on the CSAN pronto versus the DxH900 was 0.07× 109 cells/L (95% L.O.A -0.25 to 0.49) for concentrations <4.0 × 109 cells/L, which includes decision-making cut-offs for continuing clozapine treatment. Mean bias in WBC obtained on the CSAN pronto versus the DxH900 was 0.34× 109 cells/L (95% L.O.A -0.13 to 0.72) for concentrations <5.0 × 109 cells/L. The mean bias was higher (-11% for ANC, 5% for WBC) at higher concentrations. The correlations between capillary and venous samples showed more variability with mean bias of 0.20 × 109 cells/L for the ANC. Conclusions: The CSAN pronto showed acceptable performance in WBC and ANC measurements from venous and capillary samples and was approved for clinical use. This testing will facilitate treatment decisions and improve clozapine uptake and compliance.

Keywords: absolute neutrophil counts, clozapine, point of care, white blood cells

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2502 Voices of Fear: A Case Study Of Tobephobia Experienced by Female Teachers

Authors: Prakash Singh

Abstract:

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

Keywords: curriculum, female teachers, school violence, tobephobia

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2501 Autophagy Regulates Human Hepatocellular Carcinoma Tumorigenesis through Selective Degradation of Cyclin D1

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

Abstract:

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

Keywords: autophagy, cyclin D1, hepatocellular carcinoma, amiodarone

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2500 Haplotypes of the Human Leukocyte Antigen-G Different HIV-1 Groups from the Netherlands

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

Abstract:

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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2499 Anti-Infective Potential of Selected Philippine Medicinal Plant Extracts against Multidrug-Resistant Bacteria

Authors: Demetrio L. Valle Jr., Juliana Janet M. Puzon, Windell L. Rivera

Abstract:

From the various medicinal plants available in the Philippines, crude ethanol extracts of twelve (12) Philippine medicinal plants, namely: Senna alata L. Roxb. (akapulko), Psidium guajava L. (bayabas), Piper betle L. (ikmo), Vitex negundo L. (lagundi), Mitrephora lanotan (Blanco) Merr. (Lanotan), Zingiber officinale Roscoe (luya), Curcuma longa L. (Luyang dilaw), Tinospora rumphii Boerl (Makabuhay), Moringga oleifera Lam. (malunggay), Phyllanthus niruri L. (sampa-sampalukan), Centella asiatica (L.) Urban (takip kuhol), and Carmona retusa (Vahl) Masam (tsaang gubat) were studied. In vitro methods of evaluation against selected Gram-positive and Gram-negative multidrug-resistant (MDR), bacteria were performed on the plant extracts. Although five of the plants showed varying antagonistic activities against the test organisms, only Piper betle L. exhibited significant activities against both Gram-negative and Gram-positive multidrug-resistant bacteria, exhibiting wide zones of growth inhibition in the disk diffusion assay, and with the lowest concentrations of the extract required to inhibit the growth of the bacteria, as supported by the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Further antibacterial studies of the Piper betle L. leaf, obtained by three extraction methods (ethanol, methanol, supercritical CO2), revealed similar inhibitory activities against a multitude of Gram-positive and Gram-negative MDR bacteria. Thin layer chromatography (TLC) assay of the leaf extract revealed a maximum of eight compounds with Rf values of 0.92, 0.86, 0.76, 0.53, 0.40, 0.25, 0.13, and 0.013, best visualized when inspected under UV-366 nm. TLC- agar overlay bioautography of the isolated compounds showed the compounds with Rf values of 0.86 and 0.13 having inhibitory activities against Gram-positive MDR bacteria (MRSA and VRE). The compound with an Rf value of 0.86 also possesses inhibitory activity against Gram-negative MDR bacteria (CRE Klebsiella pneumoniae and MBL Acinetobacter baumannii). Gas Chromatography-Mass Spectrometry (GC-MS) was able to identify six volatile compounds, four of which are new compounds that have not been mentioned in the medical literature. The chemical compounds isolated include 4-(2-propenyl)phenol and eugenol; and the new four compounds were ethyl diazoacetate, tris(trifluoromethyl)phosphine, heptafluorobutyrate, and 3-fluoro-2-propynenitrite. Phytochemical screening and investigation of its antioxidant, cytotoxic, possible hemolytic activities, and mechanisms of antibacterial activity were also done. The results showed that the local variant of Piper betle leaf extract possesses significant antioxidant, anti-cancer and antimicrobial properties, attributed to the presence of bioactive compounds, particularly of flavonoids (condensed tannin, leucoanthocyanin, gamma benzopyrone), anthraquinones, steroids/triterpenes and 2-deoxysugars. Piper betle L. is also traditionally known to enhance wound healing, which could be primarily due to its antioxidant, anti-inflammatory and antimicrobial activities. In vivo studies on mice using 2.5% and 5% of the ethanol leaf extract cream formulations in the excised wound models significantly increased the process of wound healing in the mice subjects, the results and values of which are at par with the current antibacterial cream (Mupirocin). From the results of the series of studies, we have definitely proven the value of Piper betle L. as a source of bioactive compounds that could be developed into therapeutic agents against MDR bacteria.

Keywords: Philippine herbal medicine, multidrug-resistant bacteria, Piper betle, TLC-bioautography

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2498 Calibration of Syringe Pumps Using Interferometry and Optical Methods

Authors: E. Batista, R. Mendes, A. Furtado, M. C. Ferreira, I. Godinho, J. A. Sousa, M. Alvares, R. Martins

Abstract:

Syringe pumps are commonly used for drug delivery in hospitals and clinical environments. These instruments are critical in neonatology and oncology, where any variation in the flow rate and drug dosing quantity can lead to severe incidents and even death of the patient. Therefore it is very important to determine the accuracy and precision of these devices using the suitable calibration methods. The Volume Laboratory of the Portuguese Institute for Quality (LVC/IPQ) uses two different methods to calibrate syringe pumps from 16 nL/min up to 20 mL/min. The Interferometric method uses an interferometer to monitor the distance travelled by a pusher block of the syringe pump in order to determine the flow rate. Therefore, knowing the internal diameter of the syringe with very high precision, the travelled distance, and the time needed for that travelled distance, it was possible to calculate the flow rate of the fluid inside the syringe and its uncertainty. As an alternative to the gravimetric and the interferometric method, a methodology based on the application of optical technology was also developed to measure flow rates. Mainly this method relies on measuring the increase of volume of a drop over time. The objective of this work is to compare the results of the calibration of two syringe pumps using the different methodologies described above. The obtained results were consistent for the three methods used. The uncertainties values were very similar for all the three methods, being higher for the optical drop method due to setup limitations.

Keywords: calibration, flow, interferometry, syringe pump, uncertainty

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2497 Potential Contribution of Local Food Resources towards Sustainable Food Tourism in Nueva Vizcaya

Authors: Marvin Eslava

Abstract:

The over-arching aim of this research is to determine the potential contribution of local food resources to the tourism growth of Nueva Vizcaya. It reviews some of the underpinning concepts and to provide a set of considerations for stakeholders to maximize the opportunity of local food can offer to businesses and the wider community. The basis of the study is to develop a sustainable food tourism model for Nueva Vizcaya. For the purpose of this research, there were 60 total numbers of respondents classified as samples from a six municipality. The respondents of the study were stakeholder consisting of government official, local producers, businessman and Non-government organizations in the selected municipalities of Nueva Vizcaya. Stratified purposive sampling was the appropriate technique that was used to the local government officials and employees, NGOs including the businessmen who are associated with local food resources and local producers. The documentary study, focus group discussion and survey questionnaire was used in order to meet the objectives of the study. Kruskall Wallis test was used to test the variances the ratings of the participants. This was used in the computation of hypothesis. The study concluded that the province of Nueva Vizcaya is blessed for its rich farmlands and fertile mountain soil boasts to produce high quality agricultural products. It is a home of various different indigenous groups creating a wide range of local cuisine. The province has substantial local food development evidence by the various food tourism related resources, increase in facilities and celebrating food tourism related events. The local food resources provide extensive potential economic empowerment and help in building the identity of the province. In addition, the local food resources extensively enhance the agriculture sector and other attractions in the province. Finally, it helps to preserve the authenticity of the food culture and generated pride among all stakeholders extensively. All stakeholders have the same perception on the potential contribution of local food resources to the development of the province of Nueva Vizcaya. The public and private sectors are cognizant on their roles to support the production of local food resources in Nueva Vizcaya. Major challenges and barriers in the development of sustainable food tourism in Nueva Vizcaya include production or supply and marketing.

Keywords: local food resources, contribution, food tourism, benefits

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2496 Frequency of Polymorphism of Mrp1/Abcc1 And Mrp2/Abcc2 in Healthy Volunteers of the Center Savannah (Colombia)

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

Abstract:

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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2495 A Survey of Dynamic QoS Methods in Sofware Defined Networking

Authors: Vikram Kalekar

Abstract:

Modern Internet Protocol (IP) networks deploy traditional and modern Quality of Service (QoS) management methods to ensure the smooth flow of network packets during regular operations. SDN (Software-defined networking) networks have also made headway into better service delivery by means of novel QoS methodologies. While many of these techniques are experimental, some of them have been tested extensively in controlled environments, and few of them have the potential to be deployed widely in the industry. With this survey, we plan to analyze the approaches to QoS and resource allocation in SDN, and we will try to comment on the possible improvements to QoS management in the context of SDN.

Keywords: QoS, policy, congestion, flow management, latency, delay index terms-SDN, delay

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2494 Role of Internal and External Factors in Preventing Risky Sexual Behavior, Drug and Alcohol Abuse

Authors: Veronika Sharok

Abstract:

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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2493 Curcumin-Loaded Pickering Emulsion Stabilized by pH-Induced Self-Aggregated Chitosan Particles for Encapsulating Bioactive Compounds for Food, Flavor/Fragrance, Cosmetics, and Medicine

Authors: Rizwan Ahmed Bhutto, Noor ul ain Hira Bhutto, Mingwei Wang, Shahid Iqbal, Jiang Yi

Abstract:

Curcumin, a natural polyphenolic compound, boasts numerous health benefits; however, its industrial applications are hindered by instabilities and poor solubility. Encapsulating curcumin in Pickering emulsion presents a promising strategy to enhance its bioavailability. Yet, the development of an efficient and straightforward method to fabricate a natural emulsifier for Pickering emulsion poses a significant challenge. Chitosan has garnered attention due to its non-toxicity and excellent emulsifying properties. This study aimed to prepare four distinct types of self-aggregated chitosan particles using a pH-responsive self-assembling approach. The properties of the aggregated particles were adjusted by pH, degree of deacetylation (DDA), and molecular weight (MW), thereby controlling surface charge, size (ranging from nano to micro and floc), and contact angle. Pickering emulsions were then formulated using these various aggregated particles. As MW and pH increased and DDA decreased, the networked structures of the aggregated particles formed, resulting in highly elastic gels that were more resistant to the breakdown of Pickering emulsion at ambient temperature. With elevated temperatures, the kinetic energy of the aggregated particles increased, disrupting hydrogen bonds and potentially transforming the systems from fluids to gels. The Pickering emulsion based on aggregated particles served as a carrier for curcumin encapsulation. It was observed that DDA and MW played crucial roles in regulating drug loading, encapsulation efficiency, and release profile. This research sheds light on selecting suitable chitosan for controlling the release of bioactive compounds in Pickering emulsions, considering factors such as adjustable rheological properties, microstructure, and macrostructure. Furthermore, this study introduces an environmentally friendly and cost-effective synthesis of pH-responsive aggregate particles without the need for high-pressure homogenizers. It underscores the potential of aggregate particles with various MWs and DDAs for encapsulating other bioactive compounds, offering valuable applications in industries including food, flavor/fragrance, cosmetics, and medicine.

Keywords: chitosan, molecular weight, rheological properties, curcumin encapsulation

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2492 Metagenomics Analysis of Bacteria in Sorghum Using next Generation Sequencing

Authors: Kedibone Masenya, Memory Tekere, Jasper Rees

Abstract:

Sorghum is an important cereal crop in the world. In particular, it has attracted breeders due to capacity to serve as food, feed, fiber and bioenergy crop. Like any other plant, sorghum hosts a variety of microbes, which can either, have a neutral, negative and positive influence on the plant. In the current study, regions (V3/V4) of 16 S rRNA were targeted to extensively assess bacterial multitrophic interactions in the phyllosphere of sorghum. The results demonstrated that the presence of a pathogen has a significant effect on the endophytic bacterial community. Understanding these interactions is key to develop new strategies for plant protection.

Keywords: bacteria, multitrophic, sorghum, target sequencing

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2491 The Effects of Metformin And PCL-sorafenib Nanoparticles Co-treatment on MCF-7 Cell Culture Model of Breast Cancer

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

Abstract:

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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2490 Discovery of New Inhibitors for Colorectal Cancer Treatment

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

Abstract:

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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2489 The Effects of Highly Active Antiretroviral Therapy (HAART) on the Expression of Muc1 and P65 in a Cervical Cancer Cell Line, HCS-2

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

Abstract:

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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2488 The Association Between CYP2C19 Gene Distribution and Medical Cannabis Treatment

Authors: Vichayada Laohapiboolkul

Abstract:

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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2487 Novel Electrospun Polymeric Nanofibers Loaded Different Medicaments as Drug Delivery Systems for Regenerative Endodontics

Authors: Nura Brimo, Dilek Cokeliler Serdaroglu, Tansel Uyar, Busra Uysal, Elif Bahar Cakici, Miris Dikmen, Zerrin Canturk

Abstract:

Background: A combination of antibiotics, including metronidazole (MET), ciprofloxacin (CIP), and minocycline (MINO), has been demonstrated to disinfect bacteria in necrotic teeth before regenerative processes. It has been presented clinically that antibiotic pastes may drive to possible stem cell death and difficulties in removing from the canal system, which can limit the regenerative procedure. This study was designed to (1) synthesize nanofibrous webs containing various concentrations of different medicaments (triple, double, and calcium hydroxide,Ca(OH)2), and (2) coat thiselectrospun fibrous gutta-percha (GP) cones. Methods: Poly(vinylpyrrolidone) (PVP)-based electrospun fibrous webs were processed with low medicaments concentrations. Scanning Electron Microscopy (SEM), Energy Dispersive X-Ray Spectroscopy (EDX), and X-Ray Photoelectron Spectroscopy (XPS) were carried out to investigate fiber morphology, antibiotic incorporation, and characterized GP-coated fibrous webs, respectively. The chemical and physical properties of dentine were carried out via Fourier Transform Infrared Spectroscopy (FTIR) and Nano-SEM, respectively. The antimicrobial properties of the different fibrous webs were assessed against various bacteria by direct nanofiber/bacteria contact. Cytocompatibility was measured by applying the MTT method. Results: The mean fiber diameter of the experiment groups of medicament-containing fibers ranged in the nm scale and was significantly smaller than PVP fibers. EDX analysis confirmed the presence of medicaments in the nanofibers. XPS analysis presented a complete coating of the fibers with GPs; FTIR and Nano-SEM showed no chemical and physical configuration of intracanal medicaments on the dentine surface. Meanwhile, nanofibrous webs led to a significant reduction in the percentage of viable bacteria compared with the negative control and PVP. Conclusion: Our findings suggest that TA-NFs, DA-NFs, and Cₐ(OH)₂)-NFs coated GP cones have significant potential in eliminating intracanal bacteria, cell-friendly behavior, and clinical usage features.

Keywords: drug delivery, drug carrier, electrospinning, nano/microfibers, regenerative endodontic, morphology

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2486 Clustering of Natural and Nature Derived Compounds for Cardiovascular Disease: Pharmacophore Modeling

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

Abstract:

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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2485 Comparison Between the Radiation Resistance of n/p and p/n InP Solar Cell

Authors: Mazouz Halima, Belghachi Abdrahmane

Abstract:

Effects of electron irradiation-induced deep level defects have been studied on both n/p and p/n indium phosphide solar cells with very thin emitters. The simulation results show that n/p structure offers a somewhat better short circuit current but the p/n structure offers improved circuit voltage, not only before electron irradiation, but also after 1MeV electron irradiation with 5.1015 fluence. The simulation also shows that n/p solar cell structure is more resistant than that of p/n structure.

Keywords: InP solar cell, p/n and n/p structure, electron irradiation, output parameters

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2484 Optics Meets Microfluidics for Highly Sensitive Force Sensing

Authors: Iliya Dimitrov Stoev, Benjamin Seelbinder, Elena Erben, Nicola Maghelli, Moritz Kreysing

Abstract:

Despite the revolutionizing impact of optical tweezers in materials science and cell biology up to the present date, trapping has so far extensively relied on specific material properties of the probe and local heating has limited applications related to investigating dynamic processes within living systems. To overcome these limitations while maintaining high sensitivity, here we present a new optofluidic approach that can be used to gently trap microscopic particles and measure femtoNewton forces in a contact-free manner and with thermally limited precision.

Keywords: optofluidics, force measurements, microrheology, FLUCS, thermoviscous flows

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2483 Evaluation of the Influence of Graphene Oxide on Spheroid and Monolayer Culture under Flow Conditions

Authors: A. Zuchowska, A. Buta, M. Mazurkiewicz-Pawlicka, A. Malolepszy, L. Stobinski, Z. Brzozka

Abstract:

In recent years, graphene-based materials are finding more and more applications in biological science. As a thin, tough, transparent and chemically resistant materials, they appear to be a very good material for the production of implants and biosensors. Interest in graphene derivatives also resulted at the beginning of research about the possibility of their application in cancer therapy. Currently, the analysis of their potential use in photothermal therapy and as a drug carrier is mostly performed. Moreover, the direct anticancer properties of graphene-based materials are also tested. Nowadays, cytotoxic studies are conducted on in vitro cell culture in standard culture vessels (macroscale). However, in this type of cell culture, the cells grow on the synthetic surface in static conditions. For this reason, cell culture in macroscale does not reflect in vivo environment. The microfluidic systems, called Lab-on-a-chip, are proposed as a solution for improvement of cytotoxicity analysis of new compounds. Here, we present the evaluation of cytotoxic properties of graphene oxide (GO) on breast, liver and colon cancer cell line in a microfluidic system in two spatial models (2D and 3D). Before cell introduction, the microchambers surface was modified by the fibronectin (2D, monolayer) and poly(vinyl alcohol) (3D, spheroids) covering. After spheroid creation (3D) and cell attachment (2D, monolayer) the selected concentration of GO was introduced into microsystems. Then monolayer and spheroids viability/proliferation using alamarBlue® assay and standard microplate reader was checked for three days. Moreover, in every day of the culture, the morphological changes of cells were determined using microscopic analysis. Additionally, on the last day of the culture differential staining using Calcein AM and Propidium iodide were performed. We were able to note that the GO has an influence on all tested cell line viability in both monolayer and spheroid arrangement. We showed that GO caused higher viability/proliferation decrease for spheroids than a monolayer (this was observed for all tested cell lines). Higher cytotoxicity of GO on spheroid culture can be caused by different geometry of the microchambers for 2D and 3D cell cultures. Probably, GO was removed from the flat microchambers for 2D culture. Those results were also confirmed by differential staining. Comparing our results with the studies conducted in the macroscale, we also proved that the cytotoxic properties of GO are changed depending on the cell culture conditions (static/ flow).

Keywords: cytotoxicity, graphene oxide, monolayer, spheroid

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2482 Biophysical Analysis of the Interaction of Polymeric Nanoparticles with Biomimetic Models of the Lung Surfactant

Authors: Weiam Daear, Patrick Lai, Elmar Prenner

Abstract:

The human body offers many avenues that could be used for drug delivery. The pulmonary route, which is delivered through the lungs, presents many advantages that have sparked interested in the field. These advantages include; 1) direct access to the lungs and the large surface area it provides, and 2) close proximity to the blood circulation. The air-blood barrier of the alveoli is about 500 nm thick. The air-blood barrier consist of a monolayer of lipids and few proteins called the lung surfactant and cells. This monolayer consists of ~90% lipids and ~10% proteins that are produced by the alveolar epithelial cells. The two major lipid classes constitutes of various saturation and chain length of phosphatidylcholine (PC) and phosphatidylglycerol (PG) representing 80% of total lipid component. The major role of the lung surfactant monolayer is to reduce surface tension experienced during breathing cycles in order to prevent lung collapse. In terms of the pulmonary drug delivery route, drugs pass through various parts of the respiratory system before reaching the alveoli. It is at this location that the lung surfactant functions as the air-blood barrier for drugs. As the field of nanomedicine advances, the use of nanoparticles (NPs) as drug delivery vehicles is becoming very important. This is due to the advantages NPs provide with their large surface area and potential specific targeting. Therefore, studying the interaction of NPs with lung surfactant and whether they affect its stability becomes very essential. The aim of this research is to develop a biomimetic model of the human lung surfactant followed by a biophysical analysis of the interaction of polymeric NPs. This biomimetic model will function as a fast initial mode of testing for whether NPs affect the stability of the human lung surfactant. The model developed thus far is an 8-component lipid system that contains major PC and PG lipids. Recently, a custom made 16:0/16:1 PC and PG lipids were added to the model system. In the human lung surfactant, these lipids constitute 16% of the total lipid component. According to the author’s knowledge, there is not much monolayer data on the biophysical analysis of the 16:0/16:1 lipids, therefore more analysis will be discussed here. Biophysical techniques such as the Langmuir Trough is used for stability measurements which monitors changes to a monolayer's surface pressure upon NP interaction. Furthermore, Brewster Angle Microscopy (BAM) employed to visualize changes to the lateral domain organization. Results show preferential interactions of NPs with different lipid groups that is also dependent on the monolayer fluidity. Furthermore, results show that the film stability upon compression is unaffected, but there are significant changes in the lateral domain organization of the lung surfactant upon NP addition. This research is significant in the field of pulmonary drug delivery. It is shown that NPs within a certain size range are safe for the pulmonary route, but little is known about the mode of interaction of those polymeric NPs. Moreover, this work will provide additional information about the nanotoxicology of NPs tested.

Keywords: Brewster angle microscopy, lipids, lung surfactant, nanoparticles

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2481 Resistance of Field Populations of Rhipicephalus bursa (Acari:Ixodidae) to Lambda-Cyhalothrin Acaricide in Mazandaran Province, North of Iran

Authors: Seyyed Payman Ziapour, Ahmadali Enayati, Sadegh Kheiri, Farzaneh Sahraei-Rostami, Reza Ali Mohammadpour, Mahmoud Fazeli-Dinan, Mohsen Aarabi, Fatemeh Asgarian, Seyed Hassan Nikookar, Mohammad Sarafrazi

Abstract:

Rhipicephalus bursa (R. bursa) is a two-host ixodid tick with wide distribution in north of Iran especially in domestic animals of Mazandaran Province. The prolonged or incorrect use of chemical insecticides has led to build up of resistance in hard ticks in many areas of the world. Lack of basic information on resistance status of R. bursa was the reason behind this study to determine the susceptibility status of the species to lambda-cyhalothrin insecticide in Mazandaran Province. From May 2013 to March 2014, R. bursa ticks were collected on sheep, goat and cattle in different districts of Mazandaran Province. The engorged female ticks were reared in a controlled insectary for producing 12-18 days old larvae for larval packet test (LPT) bioassay against discriminant doses of lambda-cyhalothrin 5% EC (MAC SILAT®). 80% of ten pooled tick populations were susceptible to lambda-cyhalothrin as resistance ratios (RR50s) varied from 1 to 2.94 when compared with the most susceptible population NH-16. Only GK-12 and BF-6 populations (from plain areas of Galugah and Fereydunkenar Counties, respectively) were classified as resistant level I at LC50 level. Population NK-2 (from woodland areas of Kojour district in Nowshahr County) showed the highest resistance ratio of RR99 = 4.32 and 30% of tick populations were resistant at LC99 level. Our research showed initiation of lambda-cyhalothrin resistance in Rhipicephalus bursa populations in Mazandaran Province, Northern Iran. This is considered a warning to policy makers for disease control in the study area. This research is a part of the PhD thesis of SP. Ziapour by grant No. 92-89 in Student Research Committee, Mazandaran University of Medical Sciences, Iran.

Keywords: Rhipicephalus bursa, hard tick, lambda-cyhalothrin resistance, Iran

Procedia PDF Downloads 392
2480 A Qualitative Study to Analyze Clinical Coders’ Decision Making Process of Adverse Drug Event Admissions

Authors: Nisa Mohan

Abstract:

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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2479 Gold-Mediated Modification of Apoferritin Surface with Targeting Antibodies

Authors: Simona Dostalova, Pavel Kopel, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

Abstract:

Protein apoferritin seems to be a very promising structure for use as a nanocarrier. It is prepared from intracellular ferritin protein naturally found in most organisms. The role of ferritin proteins is to store and transport ferrous ions. Apoferritin is a hollow protein cage without ferrous ions that can be prepared from ferritin by reduction with thioglycolic acid or dithionite. The structure of apoferritin is composed of 24 protein subunits, creating a sphere with 12 nm in diameter. The inner cavity has a diameter of 8 nm. The drug encapsulation process is based on the response of apoferritin structure to the pH changes of surrounding solution. In low pH, apoferritin is disassembled into individual subunits and its structure is “opened”. It can then be mixed with any desired cytotoxic drug and after adjustment of pH back to neutral the subunits are reconnected again and the drug is encapsulated within the apoferritin particles. Excess drug molecules can be removed by dialysis. The receptors for apoferritin, SCARA5 and TfR1 can be found in the membrane of both healthy and cancer cells. To enhance the specific targeting of apoferritin nanocarrier, it is possible to modify its surface with targeting moieties, such as antibodies. To ensure sterically correct complex, we used a a peptide linker based on a protein G with N-terminus affinity towards Fc region of antibodies. To connect the peptide to the surface of apoferritin, the C-terminus of peptide was made of cysteine with affinity to gold. The surface of apoferritin with encapsulated doxorubicin (ApoDox) was coated either with gold nanoparticles (ApoDox-Nano) or gold (III) chloride hydrate reduced with sodium borohydride (ApoDox-HAu). The applied amount of gold in form of gold (III) chloride hydrate was 10 times higher than in the case of gold nanoparticles. However, after removal of the excess unbound ions by electrophoretic separation, the concentration of gold on the surface of apoferritin was only 6 times higher for ApoDox-HAu in comparison with ApoDox-Nano. Moreover, the reduction with sodium borohydride caused a loss of doxorubicin fluorescent properties (excitation maximum at 480 nm with emission maximum at 600 nm) and thus its biological activity. Fluorescent properties of ApoDox-Nano were similar to the unmodified ApoDox, therefore it was more suited for the intended use. To evaluate the specificity of apoferritin modified with antibodies, we used ELISA-like method with the surface of microtitration plate wells coated by the antigen (goat anti-human IgG antibodies). To these wells, we applied ApoDox without targeting antibodies and ApoDox-Nano modified with targeting antibodies (human IgG antibodies). The amount of unmodified ApoDox on antigen after incubation and subsequent rinsing with water was 5 times lower than in the case of ApoDox-Nano modified with targeting antibodies. The modification of non-gold ApoDox with antibodies caused no change in its targeting properties. It can therefore be concluded that the demonstrated procedure allows us to create nanocarrier with enhanced targeting properties, suitable for nanomedicine.

Keywords: apoferritin, doxorubicin, nanocarrier, targeting antibodies

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2478 A Brief History of Kampo Extract Formulations for Prescription in Japan

Authors: Kazunari Ozaki, Mitsuru Kageyama, Kenki Miyazawa, Yoshio Nakamura

Abstract:

Background: Kampo (Japanese Traditional medicine) is a medicine traditionally practiced in Japan, based on ancient Chinese medicine. Most Kampo doctors have used decoction of crude drug pieces for treatment. 93% of the Kampo drugs sold in Japan are Kampo products nowadays. Of all Kampo products, 81% of them are Kampo extract formulations for prescription, which is prepared in powdered or granulated form from medicinal crude drug extracts mixed with appropriate excipient. Physicians with medical license for Western medicine prescribe these Kampo extract formulations for prescription in Japan. Objectives: Our study aims at presenting a brief history of Kampo extract formulations for prescription in Japan. Methods: Systematic searches for relevant studies were conducted using not only printed journals but also electronic journals from the bibliographic databases, such as PubMed/Medline, Ichushi-Web, and university/institutional websites, as well as search engines, such as Google and Google Scholar. Results: The first commercialization of Kampo extract formulations for general use (or OTC (over-the-counter) Kampo extract formulation) was achieved after 1957. The number of drugs has been subsequentially increased, reaching 148 Kampo extract formulation for prescription currently. Conclusion: We provide a history of Kampo extract formulations for prescription in Japan. The originality of this research is that it analyzes the background history of Kampo in parallel with relevant transitions in the government and insurance systems.

Keywords: health insurance system, history, Kampo, Kampo extract formulation for prescription, OTC Kampo extract formulation, pattern corresponding prescription (Ho-sho-so-tai) system

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2477 Impact of Microwave Heating Temperatures on the Pharmaceutical Powder Characteristics

Authors: Maha Al-Ali, Selvakannan Periasamy, Rajarathinam Parthasarathy

Abstract:

Drying temperature is an important factor impacting the physicochemical properties of the dried materials, particularly the pharmaceutical powders. Drying of pharmaceuticals by using microwave radiation is very limited, and the available information about the interaction between the electromagnetic radiations and the pharmaceutical material is still scarce. Therefore, microwave drying process is employed in this work to dry the wet (moisturised) granules of the formulated naproxen-sodium drug. This study aims to investigate the influences of the microwave radiation temperatures on the moisture removal, the crystalline structure, the size and morphology of the dried naproxen-sodium particles, and identify any potential changes in the chemical groups of the drug. In this work, newly formulated naproxen-sodium is prepared and moisturized by wet granulation process and hence dried by using microwave radiation at different temperatures. Moisture analyzer, Fourier-transform infrared spectroscopy, powder X-ray diffraction, and scanning electron microscope are used to characterise the non-moisturised powder (reference powder), the moisturised granules, and the dried particles. The results show that microwave drying of naproxen-sodium at high drying temperature is more efficient than that at low temperatures in terms of the moisture removal. Although there is no significant change in the chemical structure of the dried particles, the particle size, crystallinity and morphology are relatively changed with changing of heating temperature.

Keywords: heating temperature, microwave drying, naproxen-sodium, particle size

Procedia PDF Downloads 158
2476 Comparative Analysis of Feature Extraction and Classification Techniques

Authors: R. L. Ujjwal, Abhishek Jain

Abstract:

In the field of computer vision, most facial variations such as identity, expression, emotions and gender have been extensively studied. Automatic age estimation has been rarely explored. With age progression of a human, the features of the face changes. This paper is providing a new comparable study of different type of algorithm to feature extraction [Hybrid features using HAAR cascade & HOG features] & classification [KNN & SVM] training dataset. By using these algorithms we are trying to find out one of the best classification algorithms. Same thing we have done on the feature selection part, we extract the feature by using HAAR cascade and HOG. This work will be done in context of age group classification model.

Keywords: computer vision, age group, face detection

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