Search results for: breast cancer cell lines
Commenced in January 2007
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Edition: International
Paper Count: 5941

Search results for: breast cancer cell lines

361 Response of Planktonic and Aggregated Bacterial Cells to Water Disinfection with Photodynamic Inactivation

Authors: Thayse Marques Passos, Brid Quilty, Mary Pryce

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The interest in developing alternative techniques to obtain safe water, free from pathogens and hazardous substances, is growing in recent times. The photodynamic inactivation of microorganisms (PDI) is a promising ecologically-friendly and multi-target approach for water disinfection. It uses visible light as an energy source combined with a photosensitiser (PS) to transfer energy/electrons to a substrate or molecular oxygen generating reactive oxygen species, which cause cidal effects towards cells. PDI has mainly been used in clinical studies and investigations on its application to disinfect water is relatively recent. The majority of studies use planktonic cells. However, in their natural environments, bacteria quite often do not occur as freely suspended cells (planktonic) but in cell aggregates that are either freely floating or attached to surfaces as biofilms. Microbes can form aggregates and biofilms as a strategy to protect them from environmental stress. As aggregates, bacteria have a better metabolic function, they communicate more efficiently, and they are more resistant to biocide compounds than their planktonic forms. Among the bacteria that are able to form aggregates are members of the genus Pseudomonas, they are a very diverse group widely distributed in the environment. Pseudomonas species can form aggregates/biofilms in water and can cause particular problems in water distribution systems. The aim of this study was to evaluate the effectiveness of photodynamic inactivation in killing a range of planktonic cells including Escherichia coli DSM 1103, Staphylococcus aureus DSM 799, Shigella sonnei DSM 5570, Salmonella enterica and Pseudomonas putida DSM 6125, and aggregating cells of Pseudomonas fluorescens DSM 50090, Pseudomonas aeruginosa PAO1. The experiments were performed in glass Petri dishes, containing the bacterial suspension and the photosensitiser, irradiated with a multi-LED (wavelengths 430nm and 660nm) for different time intervals. The responses of the cells were monitored using the pour plate technique and confocal microscopy. The study showed that bacteria belonging to Pseudomonads group tend to be more tolerant to PDI. While E. coli, S. aureus, S. sonnei and S. enterica required a dosage ranging from 39.47 J/cm2 to 59.21 J/cm2 for a 5 log reduction, Pseudomonads needed a dosage ranging from 78.94 to 118.42 J/cm2, a higher dose being required when the cells aggregated.

Keywords: bacterial aggregation, photoinactivation, Pseudomonads, water disinfection

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360 Perovskite Nanocrystals and Quantum Dots: Advancements in Light-Harvesting Capabilities for Photovoltaic Technologies

Authors: Mehrnaz Mostafavi

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Perovskite nanocrystals and quantum dots have emerged as leaders in the field of photovoltaic technologies, demonstrating exceptional light-harvesting abilities and stability. This study investigates the substantial progress and potential of these nano-sized materials in transforming solar energy conversion. The research delves into the foundational characteristics and production methods of perovskite nanocrystals and quantum dots, elucidating their distinct optical and electronic properties that render them well-suited for photovoltaic applications. Specifically, it examines their outstanding light absorption capabilities, enabling more effective utilization of a wider solar spectrum compared to traditional silicon-based solar cells. Furthermore, this paper explores the improved durability achieved in perovskite nanocrystals and quantum dots, overcoming previous challenges related to degradation and inconsistent performance. Recent advancements in material engineering and techniques for surface passivation have significantly contributed to enhancing the long-term stability of these nanomaterials, making them more commercially feasible for solar cell usage. The study also delves into the advancements in device designs that incorporate perovskite nanocrystals and quantum dots. Innovative strategies, such as tandem solar cells and hybrid structures integrating these nanomaterials with conventional photovoltaic technologies, are discussed. These approaches highlight synergistic effects that boost efficiency and performance. Additionally, this paper addresses ongoing challenges and research endeavors aimed at further improving the efficiency, stability, and scalability of perovskite nanocrystals and quantum dots in photovoltaics. Efforts to mitigate concerns related to material degradation, toxicity, and large-scale production are actively pursued, paving the way for broader commercial application. In conclusion, this paper emphasizes the significant role played by perovskite nanocrystals and quantum dots in advancing photovoltaic technologies. Their exceptional light-harvesting capabilities, combined with increased stability, promise a bright future for next-generation solar cells, ushering in an era of highly efficient and cost-effective solar energy conversion systems.

Keywords: perovskite nanocrystals, quantum dots, photovoltaic technologies, light-harvesting, solar energy conversion, stability, device designs

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359 Experimental Activity on the Photovoltaic Effect

Authors: Salomão Manuel Francisco, Manuel António Salgueiro Da Silva, Bento Filipe Barreiras Pinto Cavadas, Teresa Monteiro Seixas

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In bachelor's degrees in Physics Education framework in Angola, and to a certain extent, within the community of Portuguese language countries (CPLP), teaching methodologies rely heavily on theoretical memorization and mathematical demonstrations. This approach often discourages students, particularly the female population, as the reliance on theoretical mathematical demonstrations generates the perception of Physics as an arduous, challenging discipline. To address this challenge and recognize the value of practical application as an evaluative criterion of material truth, we propose a practical activity in Environmental Physics that will be shared with Angolan higher education teachers, who will receive full scaffolding and support from the authors. These teachers, adopting and developing similar activities in a classroom setting, will contribute to the environmental education framework as well. Additionally, this work aligns with different goals of UNESCO's 2030 agenda, namely, specifically, goals 4, 5, 7, 11, 13, and 17. The experimental activity developed in this work is centered around the demonstration of the photovoltaic effect and its application for renewable energy production. The first objective of the activity is to study the variation of electrical power supplied by a photovoltaic system (PV) to an electrical circuit as the angle of light incidence changes. Students can observe that the power supplied to the circuit is greater when light rays fall perpendicularly on the PV. However, as the angle of incidence increases, resulting in a larger area covered by the light rays, the power supplied to the circuit decreases due to lower irradiance. The second objective is to demonstrate that the power output can be maximized by adjusting the circuit load resistance at each irradiance value. In these two parts of the activity, students can analyze experimental data taking into account the irradiance law and the equivalent circuit description of a PV cell. Through detailed data analysis, students are also expected to assess the effects of temperature on PV efficiency degradation and the efficiency enhancement provided by light concentration mechanisms. As a third objective, students can explore how the color of incident light affects the PV output power, considering the quantum nature of light and its interaction with the PV system.

Keywords: experiments, irradiation law, physic teaching, photovoltaic effect

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358 Irradion: Portable Small Animal Imaging and Irradiation Unit

Authors: Josef Uher, Jana Boháčová, Richard Kadeřábek

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In this paper, we present a multi-robot imaging and irradiation research platform referred to as Irradion, with full capabilities of portable arbitrary path computed tomography (CT). Irradion is an imaging and irradiation unit entirely based on robotic arms for research on cancer treatment with ion beams on small animals (mice or rats). The platform comprises two subsystems that combine several imaging modalities, such as 2D X-ray imaging, CT, and particle tracking, with precise positioning of a small animal for imaging and irradiation. Computed Tomography: The CT subsystem of the Irradion platform is equipped with two 6-joint robotic arms that position a photon counting detector and an X-ray tube independently and freely around the scanned specimen and allow image acquisition utilizing computed tomography. Irradiation measures nearly all conventional 2D and 3D trajectories of X-ray imaging with precisely calibrated and repeatable geometrical accuracy leading to a spatial resolution of up to 50 µm. In addition, the photon counting detectors allow X-ray photon energy discrimination, which can suppress scattered radiation, thus improving image contrast. It can also measure absorption spectra and recognize different materials (tissue) types. X-ray video recording and real-time imaging options can be applied for studies of dynamic processes, including in vivo specimens. Moreover, Irradion opens the door to exploring new 2D and 3D X-ray imaging approaches. We demonstrate in this publication various novel scan trajectories and their benefits. Proton Imaging and Particle Tracking: The Irradion platform allows combining several imaging modules with any required number of robots. The proton tracking module comprises another two robots, each holding particle tracking detectors with position, energy, and time-sensitive sensors Timepix3. Timepix3 detectors can track particles entering and exiting the specimen and allow accurate guiding of photon/ion beams for irradiation. In addition, quantifying the energy losses before and after the specimen brings essential information for precise irradiation planning and verification. Work on the small animal research platform Irradion involved advanced software and hardware development that will offer researchers a novel way to investigate new approaches in (i) radiotherapy, (ii) spectral CT, (iii) arbitrary path CT, (iv) particle tracking. The robotic platform for imaging and radiation research developed for the project is an entirely new product on the market. Preclinical research systems with precision robotic irradiation with photon/ion beams combined with multimodality high-resolution imaging do not exist currently. The researched technology can potentially cause a significant leap forward compared to the current, first-generation primary devices.

Keywords: arbitrary path CT, robotic CT, modular, multi-robot, small animal imaging

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357 Hepatoprotective Action of Emblica officinalis Linn. against Radiation and Lead Induced Changes in Swiss Albino Mice

Authors: R. K. Purohit

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Ionizing radiation induces cellular damage through direct ionization of DNA and other cellular targets and indirectly via reactive oxygen species which may include effects from epigenetic changes. So there is a need of hour is to search for an ideal radioprotector which could minimize the deleterious and damaging effects caused by ionizing radiation. Radioprotectors are agents which reduce the radiation effects on cell when applied prior to exposure of radiation. The aim of this study was to access the efficacy of Emblica officinalis in reducing radiation and lead induced changes in mice liver. For the present experiment, healthy male Swiss albino mice (6-8 weeks) were selected and maintained under standard conditions of temperature and light. Fruit extract of Emblica was fed orally at the dose of 0.01 ml/animal/day. The animal were divided into seven groups according to the treatment i.e. lead acetate solution as drinking water (group-II) or exposed to 3.5 or 7.0 Gy gamma radiation (group-III) or combined treatment of radiation and lead acetate (group-IV). The animals of experimental groups were administered Emblica extract seven days prior to radiation or lead acetate treatment (group V, VI and VII) respectively. The animals from all the groups were sacrificed by cervical dislocation at each post-treatment intervals of 1, 2, 4, 7, 14 and 28 days. After sacrificing the animals pieces of liver were taken out and some of them were kept at -20°C for different biochemical parameters. The histopathological changes included cytoplasmic degranulation, vacuolation, hyperaemia, pycnotic and crenated nuclei. The changes observed in the control groups were compared with the respective experimental groups. An increase in the value of total proteins, glycogen, acid phosphtase, alkaline phosphatase activity and RNA was observed up to day-14 in the non drug treated group and day 7 in the Emblica treated groups, thereafter value declined up to day-28 without reaching to normal. The value of cholesterol and DNA showed a decreasing trend up to day -14 in non drug treated groups and day-7 in drug treated groups, thereafter value elevated up to day-28. The biochemical parameters were observed in the form of increase or decrease in the values. The changes were found dose dependent. After combined treatment of radiation and lead acetate synergistic effect were observed. The liver of Emblica treated animals exhibited less severe damage as compared to non-drug treated animals at all the corresponding intervals. An early and fast recovery was also noticed in Emblica pretreated animals. Thus, it appears that Emblica is potent enough to check lead and radiation induced heptic lesion in Swiss albino mice.

Keywords: radiation, lead , emblica, mice, liver

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356 Facile Wick and Oil Flame Synthesis of High-Quality Hydrophilic Carbon Nano Onions for Flexible Binder-Free Supercapacitor

Authors: Debananda Mohapatra, Subramanya Badrayyana, Smrutiranjan Parida

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Carbon nano-onions (CNOs) are the spherical graphitic nanostructures composed of concentric shells of graphitic carbon can be hypothesized as the intermediate state between fullerenes and graphite. These are very important members in fullerene family also known as the multi-shelled fullerenes can be envisioned as promising supercapacitor electrode with high energy & power density as they provide easy access to ions at electrode-electrolyte interface due to their curvature. There is still very sparse report concerning on CNOs as electrode despite having an excellent electrodechemical performance record due to their unavailability and lack of convenient methods for their high yield preparation and purification. Keeping all these current pressing issues in mind, we present a facile scalable and straightforward flame synthesis method of pure and highly dispersible CNOs without contaminated by any other forms of carbon; hence, a post processing purification procedure is not necessary. To the best of our knowledge, this is the very first time; we developed an extremely simple, light weight, novel inexpensive, flexible free standing pristine CNOs electrode without using any binder element. Locally available daily used cotton wipe has been used for fabrication of such an ideal electrode by ‘dipping and drying’ process providing outstanding stretchability and mechanical flexibility with strong adhesion between CNOs and porous wipe. The specific capacitance 102 F/g, energy density 3.5 Wh/kg and power density 1224 W/kg at 20 mV/s scan rate are the highest values that ever recorded and reported so far in symmetrical two electrode cell configuration with 1M Na2SO4 electrolyte; indicating a very good synthesis conditions employed with optimum pore size in agreement with electrolyte ion size. This free standing CNOs electrode also showed an excellent cyclic performance and stability retaining 95% original capacity after 5000 charge –discharge cycles. Furthermore, this unique method not only affords binder free - freestanding electrode but also provide a general way of fabricating such multifunctional promising CNOs based nanocomposites for their potential device applications in flexible solar cells and lithium-ion batteries.

Keywords: binder-free, flame synthesis, flexible, carbon nano onion

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355 Application of Carbon Nanotubes as Cathodic Corrosion Protection of Steel Reinforcement

Authors: M. F. Perez, Ysmael Verde, B. Escobar, R. Barbosa, J. C. Cruz

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Reinforced concrete is one of the most important materials in the construction industry. However, in recent years the durability of concrete structures has been a worrying problem, mainly due to corrosion of reinforcing steel; the consequences of corrosion in all cases lead to shortening of the life of the structure and decrease in quality of service. Since the emergence of this problem, they have implemented different methods or techniques to reduce damage by corrosion of reinforcing steel in concrete structures; as the use of polymeric materials as coatings for the steel rod, spiked inhibitors of concrete during mixing, among others, presenting different limitations in the application of these methods. Because of this, it has been used a method that has proved effective, cathodic protection. That is why due to the properties attributed to carbon nanotubes (CNT), these could act as cathodic corrosion protection. Mounting a three-electrode electrochemical cell, carbon steel as working electrode, saturated calomel electrode (SCE) as the reference electrode, and a graphite rod as a counter electrode to close the system is performed. Samples made were subjected to a cycling process in order to compare the results in the corrosion performance of a coating composed of CNT and the others based on an anticorrosive commercial painting. The samples were tested at room temperature using an electrolyte consisting NaCl and NaOH simulating the typical pH of concrete, ranging from 12.6 to 13.9. Three test samples were made of steel rod, white, with commercial anticorrosive paint and CNT based coating; delimiting the work area to a section of 0.71 cm2. Tests cyclic voltammetry and linear voltammetry electrochemical spectroscopy each impedance of the three samples were made with a window of potential vs SCE 0.7 -1.7 a scan rate of 50 mV / s and 100 mV / s. The impedance values were obtained by applying a sine wave of amplitude 50 mV in a frequency range of 100 kHz to 100 MHz. The results obtained in this study show that the CNT based coating applied to the steel rod considerably decreased the corrosion rate compared to the commercial coating of anticorrosive paint, because the Ecorr was passed increase as the cycling process. The samples tested in all three cases were observed by light microscopy throughout the cycling process and micrographic analysis was performed using scanning electron microscopy (SEM). Results from electrochemical measurements show that the application of the coating containing carbon nanotubes on the surface of the steel rod greatly increases the corrosion resistance, compared to commercial anticorrosive coating.

Keywords: anticorrosive, carbon nanotubes, corrosion, steel

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354 Implementing the WHO Air Quality Guideline for PM2.5 Worldwide can Prevent Millions of Premature Deaths Per Year

Authors: Despina Giannadaki, Jos Lelieveld, Andrea Pozzer, John Evans

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Outdoor air pollution by fine particles ranks among the top ten global health risk factors that can lead to premature mortality. Epidemiological cohort studies, mainly conducted in United States and Europe, have shown that the long-term exposure to PM2.5 (particles with an aerodynamic diameter less than 2.5μm) is associated with increased mortality from cardiovascular, respiratory diseases and lung cancer. Fine particulates can cause health impacts even at very low concentrations. Previously, no concentration level has been defined below which health damage can be fully prevented. The World Health Organization ambient air quality guidelines suggest an annual mean PM2.5 concentration limit of 10μg/m3. Populations in large parts of the world, especially in East and Southeast Asia, and in the Middle East, are exposed to high levels of fine particulate pollution that by far exceeds the World Health Organization guidelines. The aim of this work is to evaluate the implementation of recent air quality standards for PM2.5 in the EU, the US and other countries worldwide and estimate what measures will be needed to substantially reduce premature mortality. We investigated premature mortality attributed to fine particulate matter (PM2.5) under adults ≥ 30yrs and children < 5yrs, applying a high-resolution global atmospheric chemistry model combined with epidemiological concentration-response functions. The latter are based on the methodology of the Global Burden of Disease for 2010, assuming a ‘safe’ annual mean PM2.5 threshold of 7.3μg/m3. We estimate the global premature mortality by PM2.5 at 3.15 million/year in 2010. China is the leading country with about 1.33 million, followed by India with 575 thousand and Pakistan with 105 thousand. For the European Union (EU) we estimate 173 thousand and the United States (US) 52 thousand in 2010. Based on sensitivity calculations we tested the gains from PM2.5 control by applying the air quality guidelines (AQG) and standards of the World Health Organization (WHO), the EU, the US and other countries. To estimate potential reductions in mortality rates we take into consideration the deaths that cannot be avoided after the implementation of PM2.5 upper limits, due to the contribution of natural sources to total PM2.5 and therefore to mortality (mainly airborne desert dust). The annual mean EU limit of 25μg/m3 would reduce global premature mortality by 18%, while within the EU the effect is negligible, indicating that the standard is largely met and that stricter limits are needed. The new US standard of 12μg/m3 would reduce premature mortality by 46% worldwide, 4% in the US and 20% in the EU. Implementing the AQG by the WHO of 10μg/m3 would reduce global premature mortality by 54%, 76% in China and 59% in India. In the EU and US, the mortality would be reduced by 36% and 14%, respectively. Hence, following the WHO guideline will prevent 1.7 million premature deaths per year. Sensitivity calculations indicate that even small changes at the lower PM2.5 standards can have major impacts on global mortality rates.

Keywords: air quality guidelines, outdoor air pollution, particulate matter, premature mortality

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353 Terrestrial Laser Scans to Assess Aerial LiDAR Data

Authors: J. F. Reinoso-Gordo, F. J. Ariza-López, A. Mozas-Calvache, J. L. García-Balboa, S. Eddargani

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The DEMs quality may depend on several factors such as data source, capture method, processing type used to derive them, or the cell size of the DEM. The two most important capture methods to produce regional-sized DEMs are photogrammetry and LiDAR; DEMs covering entire countries have been obtained with these methods. The quality of these DEMs has traditionally been evaluated by the national cartographic agencies through punctual sampling that focused on its vertical component. For this type of evaluation there are standards such as NMAS and ASPRS Positional Accuracy Standards for Digital Geospatial Data. However, it seems more appropriate to carry out this evaluation by means of a method that takes into account the superficial nature of the DEM and, therefore, its sampling is superficial and not punctual. This work is part of the Research Project "Functional Quality of Digital Elevation Models in Engineering" where it is necessary to control the quality of a DEM whose data source is an experimental LiDAR flight with a density of 14 points per square meter to which we call Point Cloud Product (PCpro). In the present work it is described the capture data on the ground and the postprocessing tasks until getting the point cloud that will be used as reference (PCref) to evaluate the PCpro quality. Each PCref consists of a patch 50x50 m size coming from a registration of 4 different scan stations. The area studied was the Spanish region of Navarra that covers an area of 10,391 km2; 30 patches homogeneously distributed were necessary to sample the entire surface. The patches have been captured using a Leica BLK360 terrestrial laser scanner mounted on a pole that reached heights of up to 7 meters; the position of the scanner was inverted so that the characteristic shadow circle does not exist when the scanner is in direct position. To ensure that the accuracy of the PCref is greater than that of the PCpro, the georeferencing of the PCref has been carried out with real-time GNSS, and its accuracy positioning was better than 4 cm; this accuracy is much better than the altimetric mean square error estimated for the PCpro (<15 cm); The kind of DEM of interest is the corresponding to the bare earth, so that it was necessary to apply a filter to eliminate vegetation and auxiliary elements such as poles, tripods, etc. After the postprocessing tasks the PCref is ready to be compared with the PCpro using different techniques: cloud to cloud or after a resampling process DEM to DEM.

Keywords: data quality, DEM, LiDAR, terrestrial laser scanner, accuracy

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352 Preliminary Results of Psychiatric Morbidity for Oncology Outpatients

Authors: Camille Plant, Katherine McGill, Pek Ang

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Oncology patients face a host of unique challenges, which are physical, psychological and philosophical in nature. This preliminary study aimed to explore the psychiatric morbidity of oncology patients in an outpatient setting at a major public hospital in Australia. The study found that 33 patients were referred to a Psychiatrist by a Clinical Psychologist or treating Oncologist. These patients attended an outpatient Psychiatry appointment at the Calvary Mater Hospital, Newcastle, over a 7 month period (June 2017-January 2018). Of these, 45% went on to have a follow-up appointment. The Clinical Global Impressions Scale (CGI) was used to gather symptom severity scores at baseline and at follow-up. The CGI is a clinician determined instrument that provides an assessment of global functioning. It is comprised of two companion one-item measures: the CGI-Severity (CGI-S) rates mental illness severity, and the CGI-Improvement (CGI-I) rates change in condition or improvement from initiation of treatment. Patients referred to a Psychiatrist were observed to be on average in the Markedly ill approaching Severely ill range (CGI-S average of 5.5). However, those patients who attended a follow-up appointment were on average only Moderately Ill at baseline (CGI-S average of 3.9). Despite these follow patients not being severely mentally ill initially, the contact was helpful, as their CGI-S scores improved on average to the Mildly Ill range (CGI-S average of 2.8). A Mixed ANOVA revealed that there was a significant improvement in mental illness severity post-follow-up appointment (Greenhouse-Geisser .000). There was a near even proportion of males and females attending appointments (58% female), and slightly more females attended a follow-up (60% female). Males were on average more mentally ill at baseline compared to females at baseline (male average M=3.86, female average M=3.56), and males had a greater reduction in mental illness severity on average compared to females (male average M=2.71, female average 3.00). This was approaching significance (.073) and would be important to explore with a larger sample size. Change in clinical condition for follow-up patients was also recorded. It was found that more than half of patients (53%) were observed to experience Minimal improvement in attending at least one follow-up appointment. There was no change for 27% of patients, and there were no patients who were worse at follow up. As this was a preliminary study with small sample size, future research conducted could explore whether there are any significant gender differences, such as whether males experience the significantly greater reduction in symptoms of mental illness compared to females, as well as any effects of cancer stage or type on psychiatric outcomes. Future research could also investigate outcomes for those patients who concurrently access a Clinical Psychologist alongside the Psychiatrist. A limitation of the study is that the outcome measure is a brief item rating completed by the clinician.

Keywords: clinical global impressions scale, psychiatry, morbidity, oncology, outcomes, psychiatry

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351 Hospital Malnutrition and its Impact on 30-day Mortality in Hospitalized General Medicine Patients in a Tertiary Hospital in South India

Authors: Vineet Agrawal, Deepanjali S., Medha R., Subitha L.

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Background. Hospital malnutrition is a highly prevalent issue and is known to increase the morbidity, mortality, length of hospital stay, and cost of care. In India, studies on hospital malnutrition have been restricted to ICU, post-surgical, and cancer patients. We designed this study to assess the impact of hospital malnutrition on 30-day post-discharge and in-hospital mortality in patients admitted in the general medicine department, irrespective of diagnosis. Methodology. All patients aged above 18 years admitted in the medicine wards, excluding medico-legal cases, were enrolled in the study. Nutritional assessment was done within 72 h of admission, using Subjective Global Assessment (SGA), which classifies patients into three categories: Severely malnourished, Mildly/moderately malnourished, and Normal/well-nourished. Anthropometric measurements like Body Mass Index (BMI), Triceps skin-fold thickness (TSF), and Mid-upper arm circumference (MUAC) were also performed. Patients were followed-up during hospital stay and 30 days after discharge through telephonic interview, and their final diagnosis, comorbidities, and cause of death were noted. Multivariate logistic regression and cox regression model were used to determine if the nutritional status at admission independently impacted mortality at one month. Results. The prevalence of malnourishment by SGA in our study was 67.3% among 395 hospitalized patients, of which 155 patients (39.2%) were moderately malnourished, and 111 (28.1%) were severely malnourished. Of 395 patients, 61 patients (15.4%) expired, of which 30 died in the hospital, and 31 died within 1 month of discharge from hospital. On univariate analysis, malnourished patients had significantly higher morality (24.3% in 111 Cat C patients) than well-nourished patients (10.1% in 129 Cat A patients), with OR 9.17, p-value 0.007. On multivariate logistic regression, age and higher Charlson Comorbidity Index (CCI) were independently associated with mortality. Higher CCI indicates higher burden of comorbidities on admission, and the CCI in the expired patient group (mean=4.38) was significantly higher than that of the alive cohort (mean=2.85). Though malnutrition significantly contributed to higher mortality on univariate analysis, it was not an independent predictor of outcome on multivariate logistic regression. Length of hospitalisation was also longer in the malnourished group (mean= 9.4 d) compared to the well-nourished group (mean= 8.03 d) with a trend towards significance (p=0.061). None of the anthropometric measurements like BMI, MUAC, or TSF showed any association with mortality or length of hospitalisation. Inference. The results of our study highlight the issue of hospital malnutrition in medicine wards and reiterate that malnutrition contributes significantly to patient outcomes. We found that SGA performs better than anthropometric measurements in assessing under-nutrition. We are of the opinion that the heterogeneity of the study population by diagnosis was probably the primary reason why malnutrition by SGA was not found to be an independent risk factor for mortality. Strategies to identify high-risk patients at admission and treat malnutrition in the hospital and post-discharge are needed.

Keywords: hospitalization outcome, length of hospital stay, mortality, malnutrition, subjective global assessment (SGA)

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350 Anti-Neuroinflammatory and Anti-Apoptotic Efficacy of Equol, against Lipopolysaccharide Activated Microglia and Its Neurotoxicity

Authors: Lalita Subedi, Jae Kyoung Chae, Yong Un Park, Cho Kyo Hee, Lee Jae Hyuk, Kang Min Cheol, Sun Yeou Kim

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Neuroinflammation may mediate the relationship between low levels of estrogens and neurodegenerative disease. Estrogens are neuroprotective and anti-inflammatory in neurodegenerative disease models. Due to the long term side effects of estrogens, researches have been focused on finding an effective phytoestrogens for biological activities. Daidzein present in soybeans and its active metabolite equol (7-hydroxy-3-(4'-hydroxyphenyl)-chroman) bears strong antioxidant and anticancer showed more potent anti-inflammatory and neuroprotective role in neuroinflammatory model confirmed its in vitro activity with molecular mechanism through NF-κB pathway. Three major CNS cells Microglia (BV-2), Astrocyte (C6), Neuron (N2a) were used to find the effect of equol in inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), MAPKs signaling proteins, apoptosis related proteins by western blot analysis. Nitric oxide (NO) and prostaglandin E2 (PGE2) was measured by the Gries method and ELISA, respectively. Cytokines like tumor necrosis factor-α (TNF-α) and IL-6 were also measured in the conditioned medium of LPS activated cells with or without equol. Equol inhibited the NO production, PGE-2 production and expression of COX-2 and iNOS in LPS-stimulated microglial cells at a dose dependent without any cellular toxicity. At the same time Equol also showed promising effect in modulation of MAPK’s and nuclear factor kappa B (NF-κB) expression with significant inhibition of the production of proinflammatory cytokine like interleukin -6 (IL-6), and tumor necrosis factor -α (TNF-α). Additionally, it inhibited the LPS activated microglia-induced neuronal cell death by downregulating the apoptotic phenomenon in neuronal cells. Furthermore, equol increases the production of neurotrophins like NGF and increase the neurite outgrowth as well. In conclusion the natural daidzein metabolite equol are more active than daidzein, which showed a promising effectiveness as an anti-neuroinflammatory and neuroprotective agent via downregulating the LPS stimulated microglial activation and neuronal apoptosis. This work was supported by Brain Korea 21 Plus project and High Value-added Food Technology Development Program 114006-4, Ministry of Agriculture, Food and Rural Affairs.

Keywords: apoptosis, equol, neuroinflammation, phytoestrogen

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349 In Vivo Antiulcer and Anti-Helicobacter pylori Activity of Geraniol on Acetic Acid plus Helicobacter pylori Induced Ulcer in Rats

Authors: Subrat Kumar Bhattamisra, Vivian Lee Yean Yan, Chin Koh Lee, Chew Hui Kuean, Yun Khoon Liew, Mayuren Candasamy

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Geraniol, an acyclic monoterpenoid is the main active constituent in the essential oils of rose and palmorosa. Antioxidant, antibacterial, anticancer and antiulcer activity of geraniol was reported by many researchers. The present investigation was designed to study in vivo antiulcer and anti-Helicobacter pylori activity of geraniol. Antiulcer and anti-H. pylori activity of geraniol was evaluated on acetic acid plus H. pylori induced ulcer in rats. Acetic acid (0.03 mL) was injected to the sub-serosal layer of the stomach through laparotomy under anaesthesia. Orogastric inoculation of H. pylori (ATCC 43504) was done twice daily for 7 days. Geraniol (15 and 30 mg/kg), vehicle and standard drugs (Amoxicillin, 50 mg/kg; clarithromycin, 25 mg/kg & omeprazole, 20 mg/kg) was administered twice daily for 14 days. Antiulcer activity of geraniol was examined by the determination of gastric ulcer index, measuring the volume of gastric juice, pH and total acidity, myeloperoxidase activity and histopathological examination. Histopathological investigation for the presence of inflammation, white blood cell infiltration, edema, the mucosal damage was studied. The presence of H. pylori was detected by placing a biopsy sample from antral part of the stomach into rapid urease test. Ulcer index in H. pylori inoculated control group was 4.13 ± 0.85 and was significantly (P < 0.05) lowered in geraniol (30 mg/kg) and reference drug treated group. Geraniol increase the pH of the gastric juice (2.18 ± 0.13 in control vs. 4.14 ± 0.57 in geraniol 30mg/kg) and lower total acidity significantly (P < 0.01) in geraniol (15 & 30 mg/kg). Myeloperoxidase (MPO) activity was measured in stomach homogenate of all the groups. H. pylori control group has significant (P < 0.05) increase in MPO activity compared to normal control group. Geraniol (30 mg/kg) was showed significant (P < 0.05) and most effective among all the groups. Histopathological examination of rat stomach was scored and the total score for H. pylori control group was 8. After geraniol (30 mg/kg) and reference drug treatment, the histopathological score was significantly decreased and it was observed to be 3.5 and 2.0 respectively. Percentage inhibition of H. pylori infection in geraniol (30 mg/kg) and reference drug were found to be 40% and 50% respectively whereas, 100% infection in H. pylori control group was observed. Geraniol exhibited significant antiulcer and anti- H. pylori activity in the rats. Thus, geraniol has the potential for the further development as an effective medication in treating H. pylori associated ulcer.

Keywords: geraniol, helicobacter pylori atcc 43504, myeloperoxidase, ulcer

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348 Steps of the Pancreatic Differentiation in the Grass Snake (Natrix natrix) Embryos

Authors: Magdalena Kowalska, Weronika Rupik

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The pancreas is an important organ present in all vertebrate species. It contains two different tissues, exocrine and endocrine, that act as two glands in one. The development and differentiation of the pancreas in reptiles is poorly known in comparison to other vertebrates. Therefore, the aim of this study was to investigate the particular steps concerning the differentiation of the pancreas in the grass snake (Natrix natrix) embryos. For this, histological methods (including hematoxylin and eosin, and Heidenhain's AZAN staining), transmission electron microscopy and three-dimensional (3D) reconstructions from serial paraffin sections were used. The results of this study indicated that the first step of pancreas development in Natrix was the connection of the two pancreatic buds: dorsal and ventral one. Then, duct walls in both buds started to be remodeled from the multilayered to single-layered epithelium. This remodeling started in the dorsal bud and was simultaneously with the differentiation of the duct lumens which occurred by the cavition. During this process, the cells that had no contact with the mesenchyme underwent cell death named anoikis. These findings indicated that the walls of ducts in the embryonic pancreas of the grass snake were initially formed by the abundant principal and single endocrine cells. Later the basal and goblet cells differentiated. Among the endocrine cells, as the first the B and A cells differentiated, then the D and PP cells. The next step of the pancreatic development was the withdrawing of the endocrine cells from the duct walls to form the pancreatic islets. The endocrine cells and islets were found only in the dorsal part of the pancreas in Natrix embryos what is different than in other vertebrate species. The islets were formed mainly by the A cells. Simultaneously, with the differentiation of the endocrine pancreas, the acinar tissue started to differentiate. The source of the acinar cells were pancreatic ducts similar as in other vertebrates. The acini formation began at the proximal part of the pancreas and went towards the caudal direction. Differentiating pancreatic ducts developed into the branched system that can be divided into extralobular, intralobular, and intercalated ducts, similarly as in other vertebrate species. However, the pattern of branching was different. In conclusions, particular steps of the pancreas differentiation in the grass snake were different than in other vertebrates. It can be supposed that these differences are related to the specific topography of the snake’s internal organs and their taxonomy position. All specimens used in the study were captured according to the Polish regulations concerning the protection of wild species. Permission was granted by the Local Ethics Commission in Katowice (41/2010; 87/2015) and the Regional Directorate for Environmental Protection in Katowice (WPN.6401.257.2015.DC).

Keywords: embryogenesis, organogenesis, pancreas, Squamata

Procedia PDF Downloads 147
347 4-Channel CWDM Optical Transceiver Applying Silicon Photonics Ge-Photodiode and MZ-Modulator

Authors: Do-Won Kim, Andy Eu Jin Lim, Raja Muthusamy Kumarasamy, Vishal Vinayak, Jacky Wang Yu-Shun, Jason Liow Tsung Yang, Patrick Lo Guo Qiang

Abstract:

In this study, we demonstrate 4-channel coarse wavelength division multiplexing (CWDM) optical transceiver based on silicon photonics integrated circuits (PIC) of waveguide Ge-photodiode (Ge-PD) and Mach Zehnder (MZ)-modulator. 4-channel arrayed PICs of Ge-PD and MZ-modulator are verified to operate at 25 Gbps/ch achieving 4x25 Gbps of total data rate. 4 bare dies of single-channel commercial electronics ICs (EICs) of trans-impedance amplifier (TIA) for Ge-PD and driver IC for MZ-modulator are packaged with PIC on printed circuit board (PCB) in a chip-on-board (COB) manner. Each single-channel EIC is electrically connected to the one channel of 4-channel PICs by wire bonds to trace. The PICs have 4-channel multiplexer for MZ-modulator and 4-channel demultiplexer for Ge-PD. The 4-channel multiplexer/demultiplexer have echelle gratings for4 CWDM optic signals of which center wavelengths are 1511, 1531, 1553, and 1573 nm. Its insertion loss is around 4dB with over 15dB of extinction ratio.The dimension of 4-channel Ge-PD is 3.6x1.4x0.3mm, and its responsivity is 1A/W with dark current of less than 20 nA.Its measured 3dB bandwidth is around 20GHz. The dimension of the 4-channel MZ-modulator is 3.6x4.8x0.3mm, and its 3dB bandwidth is around 11Ghz at -2V of reverse biasing voltage. It has 2.4V•cmbyVπVL of 6V for π shift to 4 mm length modulator.5x5um of Inversed tapered mode size converter with less than 2dB of coupling loss is used for the coupling of the lensed fiber which has 5um of mode field diameter.The PCB for COB packaging and signal transmission is designed to have 6 layers in the hybrid layer structure. 0.25 mm-thick Rogers Duroid RT5880 is used as the first core dielectric layer for high-speed performance over 25 Gbps. It has 0.017 mm-thick of copper layers and its dielectric constant is 2.2and dissipation factor is 0.0009 at 10 GHz. The dimension of both single ended and differential microstrip transmission lines are calculated using full-wave electromagnetic (EM) field simulator HFSS which RF industry is using most. It showed 3dB bandwidth at around 15GHz in S-parameter measurement using network analyzer. The wire bond length for transmission line and ground connection from EIC is done to have less than 300 µm to minimize the parasitic effect to the system.Single layered capacitors (SLC) of 100pF and 1000pF are connected as close as possible to the EICs for stabilizing the DC biasing voltage by decoupling. Its signal transmission performance is under measurement at 25Gbps achieving 100Gbps by 4chx25Gbps. This work can be applied for the active optical cable (AOC) and quad small form-factor pluggable (QSFP) for high-speed optical interconnections. Its demands are quite large in data centers targeting 100 Gbps, 400 Gbps, and 1 Tbps. As the demands of high-speed AOC and QSFP for the application to intra/inter data centers increase, this silicon photonics based high-speed 4 channel CWDM scheme can have advantages not only in data throughput but also cost effectiveness since it reduces fiber cost dramatically through WDM.

Keywords: active optical cable(AOC), 4-channel coarse wavelength division multiplexing (CWDM), communication system, data center, ge-photodiode, Mach Zehnder (MZ) modulator, optical interconnections, optical transceiver, photonics integrated circuits (PIC), quad small form-factor pluggable (QSFP), silicon photonics

Procedia PDF Downloads 389
346 Towards Better Integration: Qualitative Study on Perceptions of Russian-Speaking Immigrants in Australia

Authors: Oleg Shovkovyy

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This research conducted in response to one of the most pressing questions on the agenda of many public administration offices around the world: “What could be done for better integration and assimilation of immigrants into hosting communities?” In author’s view, the answer could be suggested by immigrants themselves. They, often ‘bogged down in the past,’ snared by own idols and demons, perceive things differently, which, in turn, may result in their inability to integrate smoothly into hosting communities. Brief literature review suggests that perceptions of immigrants are completely neglected or something unsought in the current research on migrants, which, often, based on opinion polls by members of hosting communities themselves or superficial research data by various research organizations. Even those specimens that include voices of immigrants, unlikely to shed any additional light onto the problem simply because certain things are not made to speak out loud, especially to those in whose hands immigrants’ fate is (authorities). In this regard, this qualitative study, conducted by an insider to a few Russian-speaking communities, represents a unique opportunity for all stakeholders to look at the question of integration through the eyes of immigrants, from a different perspective and thus, makes research findings especially valuable for better understanding of the problem. Case study research employed ethnographic methods of gathering data where, approximately 200 Russian-speaking immigrants of first and second generations were closely observed by the Russian-speaking researcher in their usual setting, for eight months, and at different venues. The number of informal interviews with 27 key informants, with whom the researcher managed to establish a good rapport and who were keen enough to share their experiences voluntarily, were conducted. The field notes were taken at 14 locations (study sites) within the Brisbane region of Queensland, Australia. Moreover, all this time, researcher lived in dwelling of one of the immigrants and was an active participant in the social life (worship, picnics, dinners, weekend schools, concerts, cultural events, social gathering, etc.) of observed communities, whose members, to a large extent, belong to various religious lines of the Russian and Protestant Church. It was found that the majority of immigrants had experienced some discrimination in matters of hiring, employment, recognition of educational qualifications from home countries, and simply felt a sort of dislike from society in various everyday situations. Many noted complete absences or very limited state assistance in terms of employment, training, education, and housing. For instance, the Australian Government Department of Human Services not only does not stimulate job search but, on the contrary, encourages to refuse short-term works and employment. On the other hand, offered free courses on adaptation, and the English language proved to be ineffective and unpopular amongst immigrants. Many interviewees have reported overstated requirements for English proficiency and local work experience, whereas it was not critical for the given task or job. Based on the result of long-term monitoring, the researcher also had the courage to assert the negative and decelerating roles of immigrants’ communities, particularly religious communities, on processes of integration and assimilation. The findings suggest that governments should either change current immigration policies in the direction of their toughening or to take more proactive and responsible role in dealing with immigrant-related issues; for instance, increasing assistance and support to all immigrants and probably, paying more attention to and taking stake in managing and organizing lives of immigrants’ communities rather, simply leaving it all to chance.

Keywords: Australia, immigration, integration, perceptions

Procedia PDF Downloads 198
345 Effect of Inoculum Ratio on Dark Fermentative Hydrogen Production

Authors: Zeynep Yilmazer Hitit, Patrick C. Hallenbeck

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Fuel reserve requirements due to depletion of fossil fuels have increased interest in biohydrogen since the 1990’s. In fermentative hydrogen production, pure, mixed, and co-cultures can be used to produce hydrogen. Several previous studies have evaluated hydrogen production by pure cultures of Clostridium butyricum or Enterobacter aerogenes. Evaluating hydrogen production by co-culture of these microorganisms is an interestıng approach since E. aerogenes is a facultative microorganism with resistance to oxygen in contrast to the strict anaerobe C. butyricum, and therefore has the ability to maintain anaerobic conditions. It was found that using co-cultures of facultative E. aerogenes (as a reducing agent and H2 producer) and the obligate anaerobe C. butyricum for producing hydrogen increases the yield of hydrogen by about 50% compared to C. butyricum by itself. Also, using different types of microorganisms for hydrogen production eliminates the need to use expensive reducing agents. C. butyricum strain pre-cultured anaerobically at 37 0C for 15h by inoculating 100 mL of GP medium (pH 6.8) consisting of 1% glucose, 2% polypeptone, 0.2% KH2PO4, 0.05% yeast extract, 0.05% MgSO4. 7H2O and E. aerogenes strain was pre-cultured aerobically at 30 0C, 150 rpm for 9 h by inoculating 100 mL of TGY medium (pH 6.8), consisting of 0.1% glucose, 0.5% tryptone, 0.1% K2HPO4, 0.5% yeast extract. All duplicate batch experiments were conducted in 100 mL bottles with different inoculum ratios of Clostridium butyricum and Enterobater aerogenes (C:E) using 5x diluted rich media (GP) consisting of 2 g/L glucose, 4g/L polypeptone, 0.4 g/L KH2PO4, 0.1 g/L yeast extract, 0.1 MgSO4.7H2O. The range of inoculum ratio of C. butyricum to E. aerogenes were 2:1,4:1,8:1, 1:2,1:4, 1:8, 1:0, 0:1. Using glucose as a carbon source aided in the observation of microbial behavior as well as making the effect of inoculum ratio more evident. Nearly all the glucose in the medium was used to produce hydrogen, except at a 1:0 ratio of inoculum (i.e. containing only C. butyricum). Low glucose consumption leads to a higher hydrogen yield due to cumulative hydrogen production and consumption of glucose, but not as much as C:E, 8:1. The lowest hydrogen yield was achieved in 1:8 inoculum ratio of C:E, 71.9 mL, 1.007±0.01 mol H2/mol glucose and the highest cumulative hydrogen, hydrogen yield and dry cell weight were achieved in 8:1 inoculum ratio of C:E, 117.4 mL, 2.035±0.082 mol H2/mol glucose, 0.4 g/L respectively. In this study effect of inoculum ratio on dark fermentative biohydrogen production using C. butyricum and E. aerogenes was investigated. The maximum hydrogen yield of 2.035mol H2/mol glucose was obtained using 2g/L glucose, an initial pH of 6 and an inoculum ratio of C. butyricum to E. aerogenes of 8:1. Results showed that inoculum ratio is an important parameter on hydrogen production due to competition between the two microorganisms in using substrate for growth and production of by-products. The results presented here could be of great significance for further waste management studies using co-culture hydrogen production.

Keywords: biohydrogen, Clostridium butyricum, dark fermentation, Enterobacter aerogenes, inoculum ratio in biohydrogen production

Procedia PDF Downloads 212
344 Kinetic Modelling of Fermented Probiotic Beverage from Enzymatically Extracted Annona Muricata Fruit

Authors: Calister Wingang Makebe, Wilson Ambindei Agwanande, Emmanuel Jong Nso, P. Nisha

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Traditional liquid-state fermentation processes of Annona muricata L. juice can result in fluctuating product quality and quantity due to difficulties in control and scale up. This work describes a laboratory-scale batch fermentation process to produce a probiotic Annona muricata L. enzymatically extracted juice, which was modeled using the Doehlert design with independent extraction factors being incubation time, temperature, and enzyme concentration. It aimed at a better understanding of the traditional process as an initial step for future optimization. Annona muricata L. juice was fermented with L. acidophilus (NCDC 291) (LA), L. casei (NCDC 17) (LC), and a blend of LA and LC (LCA) for 72 h at 37 °C. Experimental data were fitted into mathematical models (Monod, Logistic and Luedeking and Piret models) using MATLAB software, to describe biomass growth, sugar utilization, and organic acid production. The optimal fermentation time was obtained based on cell viability, which was 24 h for LC and 36 h for LA and LCA. The model was particularly effective in estimating biomass growth, reducing sugar consumption, and lactic acid production. The values of the determination coefficient, R2, were 0.9946, 0.9913 and 0.9946, while the residual sum of square error, SSE, was 0.2876, 0.1738 and 0.1589 for LC, LA and LCA, respectively. The growth kinetic parameters included the maximum specific growth rate, µm, which was 0.2876 h-1, 0.1738 h-1 and 0.1589 h-1 as well as the substrate saturation, Ks, with 9.0680 g/L, 9.9337 g/L and 9.0709 g/L respectively for LC, LA and LCA. For the stoichiometric parameters, the yield of biomass based on utilized substrate (YXS) was 50.7932, 3.3940 and 61.0202, and the yield of product based on utilized substrate (YPS) was 2.4524, 0.2307 and 0.7415 for LC, LA, and LCA, respectively. In addition, the maintenance energy parameter (ms) was 0.0128, 0.0001 and 0.0004 with respect to LC, LA and LCA. With the kinetic model proposed by Luedeking and Piret for lactic acid production rate, the growth associated, and non-growth associated coefficients were determined as 1.0028 and 0.0109, respectively. The model was demonstrated for batch growth of LA, LC, and LCA in Annona muricata L. juice. The present investigation validates the potential of Annona muricata L. based medium for heightened economical production of a probiotic medium.

Keywords: L. acidophilus, L. casei, fermentation, modelling, kinetics

Procedia PDF Downloads 47
343 An Easy Approach for Fabrication of Macroporous Apatite-Based Bone Cement Used As Potential Trabecular Bone Substitute

Authors: Vimal Kumar Dewangan, T. S. Sampath Kumar, Mukesh Doble, Viju Daniel Varghese

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The apatite-based, i.e., calcium-deficient hydroxyapatite (CDHAp) bone cement is well-known potential bone graft/substitute in orthopaedics due to its similar chemical composition with natural bone minerals. Therefore, an easy approach was attempted to fabricate the apatite-based (CDHAp) bone cement with improved injectability, bioresorbability, and macroporosity. In this study, the desired bone cement was developed by mixing the solid phase (consisting of wet chemically synthesized nanocrystalline hydroxyapatite and commercially available (synthetic) tricalcium phosphate) and the liquid phase (consisting of cement binding accelerator with few biopolymers in a dilute acidic solution) along with a liquid porogen as polysorbate or a solid porogen as mannitol (for comparison) in an optimized liquid-to-powder ratio. The fabricated cement sets within clinically preferred setting time (≤20 minutes) are better injectable (>70%) and also stable at ~7.3-7.4 (physiological pH). The CDHAp phased bone cement was resulted by immersing the fabricated after-set cement in phosphate buffer solution and other similar artificial body fluids and incubated at physiological conditions for seven days, confirmed through the X-ray diffraction and Fourier transform-infrared spectroscopy analyses. The so-formed synthetic apatite-based bone cement holds the acceptable compressive strength (within the range of trabecular bone) with average interconnected pores size falls in a macropores range (~50-200μm) inside the cement, verified by scanning electron microscopy (SEM), mercury intrusion porosimetry and micro-CT analysis techniques. Also, it is biodegradable (degrades ~19-22% within 10-12 weeks) when incubated in artificial body fluids under physiological conditions. The biocompatibility study of the bone cement, when incubated with MG63 cells, shows a significant increase in the cell viability after 3rd day of incubation compared with the control, and the cells were well-attached and spread completely on the surface of the bone cement, confirmed through SEM and fluorescence microscopy analyses. With this all, we can conclude that the developed synthetic macroporous apatite-based bone cement may have the potential to become promising material used as a trabecular bone substitute.

Keywords: calcium deficient hydroxyapatite, synthetic apatite-based bone cement, injectability, macroporosity, trabecular bone substitute

Procedia PDF Downloads 66
342 Engine Thrust Estimation by Strain Gauging of Engine Mount Assembly

Authors: Rohit Vashistha, Amit Kumar Gupta, G. P. Ravishankar, Mahesh P. Padwale

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Accurate thrust measurement is required for aircraft during takeoff and after ski-jump. In a developmental aircraft, takeoff from ship is extremely critical and thrust produced by the engine should be known to the pilot before takeoff so that if thrust produced is not sufficient then take-off can be aborted and accident can be avoided. After ski-jump, thrust produced by engine is required because the horizontal speed of aircraft is less than the normal takeoff speed. Engine should be able to produce enough thrust to provide nominal horizontal takeoff speed to the airframe within prescribed time limit. The contemporary low bypass gas turbine engines generally have three mounts where the two side mounts transfer the engine thrust to the airframe. The third mount only takes the weight component. It does not take any thrust component. In the present method of thrust estimation, the strain gauging of the two side mounts is carried out. The strain produced at various power settings is used to estimate the thrust produced by the engine. The quarter Wheatstone bridge is used to acquire the strain data. The engine mount assembly is subjected to Universal Test Machine for determination of equivalent elasticity of assembly. This elasticity value is used in the analytical approach for estimation of engine thrust. The estimated thrust is compared with the test bed load cell thrust data. The experimental strain data is also compared with strain data obtained from FEM analysis. Experimental setup: The strain gauge is mounted on the tapered portion of the engine mount sleeve. Two strain gauges are mounted on diametrically opposite locations. Both of the strain gauges on the sleeve were in the horizontal plane. In this way, these strain gauges were not taking any strain due to the weight of the engine (except negligible strain due to material's poison's ratio) or the hoop's stress. Only the third mount strain gauge will show strain when engine is not running i.e. strain due to weight of engine. When engine starts running, all the load will be taken by the side mounts. The strain gauge on the forward side of the sleeve was showing a compressive strain and the strain gauge on the rear side of the sleeve shows a tensile strain. Results and conclusion: the analytical calculation shows that the hoop stresses dominate the bending stress. The estimated thrust by strain gauge shows good accuracy at higher power setting as compared to lower power setting. The accuracy of estimated thrust at max power setting is 99.7% whereas at lower power setting is 78%.

Keywords: engine mounts, finite elements analysis, strain gauge, stress

Procedia PDF Downloads 449
341 Insectivorous Medicinal Plant Drosera Ecologyand its Biodiversity Conservation through Tissue Culture and Sustainable Biotechnology

Authors: Sushil Pradhan

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Biotechnology contributes to sustainable development in several ways such as biofertilizer production, biopesticide production and management of environmental pollution, tissue culture and biodiversity conservation in vitro, in vivo and in situ, Insectivorous medicinal plant Drosera burmannii Vahl belongs to the Family-Droseraceae under Order-Caryophyllales, Dicotyledoneae, Angiospermeae which has 31 (thirty one) living genera and 194 species besides 7 (seven) extinct (fossil) genera. Locally it is known as “Patkanduri” in Odia. Its Hindi name is “Mukhajali” and its English name is “Sundew”. The earliest species of Drosera was first reported in 1753 by Carolous Linnaeus called Drosera indica L (Indian Sundew). The latest species of Drosera reported by Fleisch A, Robinson, AS, McPherson S, Heinrich V, Gironella E and Madulida D.A. (2011) is Drosera ultramafica from Malaysia. More than 50 % species of Drosera have been reported from Australia and next to Australia is South Africa. India harbours only 3 species such as D. indica L, Drosera burmannii Vahl and D. peltata L. From our Odisha only D. burmannii Vahl is being reported for the first time from the district of Subarnapur near Sonepur (Arjunpur Reserve Forest Area). Drosera plant is autotrophic but to supplement its Nitrogen (N2) requirement it adopts heterotrophic mode of nutrition (insectivorous/carnivorous) as well. The colour of plant in mostly red and about 20-30cm in height with beautiful pink or white pentamerous flowers. Plants grow luxuriantly during November to February in shady and moist places near small water bodies of running water stream. Medicinally it is a popular herb in the locality for the treatment of cold and cough in children in rainy season by the local Doctors (Kabiraj and Baidya). In the present field investigation an attempt has been made to understand the unique reproductive phase and life cycle of the plant thereby planning for its conservation and propagation through various techniques of tissue culture and biotechnology. More importantly besides morphological and anatomical studies, cytological investigation is being carried out to find out the number of chromosomes in the cell and its genomics as there is no such report as yet for Drosera burmannii Vahl. The ecological significance and biodiversity conservation of Drosera with special reference to energy, environmental and chemical engineering has been discussed in the research paper presentation.

Keywords: insectivorous, medicinal, drosera, biotechnology, chromosome, genome

Procedia PDF Downloads 360
340 Bioactive Substances-Loaded Water-in-Oil/Oil-in-Water Emulsions for Dietary Supplementation in the Elderly

Authors: Agnieszka Markowska-Radomska, Ewa Dluska

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Maintaining a bioactive substances dense diet is important for the elderly, especially to prevent diseases and to support healthy ageing. Adequate bioactive substances intake can reduce the risk of developing chronic diseases (e.g. cardiovascular, osteoporosis, neurodegenerative syndromes, diseases of the oral cavity, gastrointestinal (GI) disorders, diabetes, and cancer). This can be achieved by introducing a comprehensive supplementation of components necessary for the proper functioning of the ageing body. The paper proposes the multiple emulsions of the W1/O/W2 (water-in-oil-in-water) type as carriers for effective co-encapsulation and co-delivery of bioactive substances in supplementation of the elderly. Multiple emulsions are complex structured systems ("drops in drops"). The functional structure of the W1/O/W2 emulsion enables (i) incorporation of one or more bioactive components (lipophilic and hydrophilic); (ii) enhancement of stability and bioavailability of encapsulated substances; (iii) prevention of interactions between substances, as well as with the external environment, delivery to a specific location; and (iv) release in a controlled manner. The multiple emulsions were prepared by a one-step method in the Couette-Taylor flow (CTF) contactor in a continuous manner. In general, a two-step emulsification process is used to obtain multiple emulsions. The paper contains a proposal of emulsion functionalization by introducing pH-responsive biopolymer—carboxymethylcellulose sodium salt (CMC-Na) to the external phase, which made it possible to achieve a release of components controlled by the pH of the gastrointestinal environment. The membrane phase of emulsions was soybean oil. The W1/O/W2 emulsions were evaluated for their characteristics (drops size/drop size distribution, volume packing fraction), encapsulation efficiency and stability during storage (to 30 days) at 4ºC and 25ºC. Also, the in vitro multi-substance co-release process were investigated in a simulated gastrointestinal environment (different pH and composition of release medium). Three groups of stable multiple emulsions were obtained: emulsions I with co-encapsulated vitamins B12, B6 and resveratrol; emulsions II with vitamin A and β-carotene; and emulsions III with vitamins C, E and D3. The substances were encapsulated in the appropriate emulsion phases depending on the solubility. For all emulsions, high encapsulation efficience (over 95%) and high volume packing fraction of internal droplets (0.54-0.76) were reached. In addition, due to the presence of a polymer (CMC-Na) with adhesive properties, high encapsulation stability during emulsions storage were achieved. The co-release study of encapsulated bioactive substances confirmed the possibility to modify the release profiles. It was found that the releasing process can be controlled through the composition, structure, physicochemical parameters of emulsions and pH of the release medium. The results showed that the obtained multiple emulsions might be used as potential liquid complex carriers for controlled/modified/site-specific co-delivery of bioactive substances in dietary supplementation in the elderly.

Keywords: bioactive substance co-release, co-encapsulation, elderly supplementation, multiple emulsion

Procedia PDF Downloads 176
339 Coulomb-Explosion Driven Proton Focusing in an Arched CH Target

Authors: W. Q. Wang, Y. Yin, D. B. Zou, T. P. Yu, J. M. Ouyang, F. Q. Shao

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High-energy-density state, i.e., matter and radiation at energy densities in excess of 10^11 J/m^3, is related to material, nuclear physics, astrophysics, and geophysics. Laser-driven particle beams are better suited to heat the matter as a trigger due to their unique properties of ultrashort duration and low emittance. Compared to X-ray and electron sources, it is easier to generate uniformly heated large-volume material for the proton and ion beams because of highly localized energy deposition. With the construction of state-of-art high power laser facilities, creating of extremely conditions of high-temperature and high-density in laboratories becomes possible. It has been demonstrated that on a picosecond time scale the solid density material can be isochorically heated to over 20 eV by the ultrafast proton beam generated from spherically shaped targets. For the above-mentioned technique, the proton energy density plays a crucial role in the formation of warm dense matter states. Recently, several methods have devoted to realize the focusing of the accelerated protons, involving externally exerted static-fields or specially designed targets interacting with a single or multi-pile laser pulses. In previous works, two co-propagating or opposite direction laser pulses are employed to strike a submicron plasma-shell. However, ultra-high pulse intensities, accurately temporal synchronization and undesirable transverse instabilities for a long time are still intractable for currently experimental implementations. A mechanism of the focusing of laser-driven proton beams from two-ion-species arched targets is investigated by multi-dimensional particle-in-cell simulations. When an intense linearly-polarized laser pulse impinges on the thin arched target, all electrons are completely evacuated, leading to a Coulomb-explosive electric-field mostly originated from the heavier carbon ions. The lighter protons in the moving reference frame by the ionic sound speed will be accelerated and effectively focused because of this radially isotropic field. At a 2.42×10^21 W/cm^2 laser intensity, a ballistic proton bunch with its energy-density as high as 2.15×10^17 J/m^3 is produced, and the highest proton energy and the focusing position agree well with that from the theory.

Keywords: Coulomb explosion, focusing, high-energy-density, ion acceleration

Procedia PDF Downloads 307
338 A Stepped Care mHealth-Based Approach for Obesity with Type 2 Diabetes in Clinical Health Psychology

Authors: Gianluca Castelnuovo, Giada Pietrabissa, Gian Mauro Manzoni, Margherita Novelli, Emanuele Maria Giusti, Roberto Cattivelli, Enrico Molinari

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Diabesity could be defined as a new global epidemic of obesity and being overweight with many complications and chronic conditions. Such conditions include not only type 2 diabetes, but also cardiovascular diseases, hypertension, dyslipidemia, hypercholesterolemia, cancer, and various psychosocial and psychopathological disorders. The financial direct and indirect burden (considering also the clinical resources involved and the loss of productivity) is a real challenge in many Western health-care systems. Recently the Lancet journal defined diabetes as a 21st-century challenge. In order to promote patient compliance in diabesity treatment reducing costs, evidence-based interventions to improve weight-loss, maintain a healthy weight, and reduce related comorbidities combine different treatment approaches: dietetic, nutritional, physical, behavioral, psychological, and, in some situations, pharmacological and surgical. Moreover, new technologies can provide useful solutions in this multidisciplinary approach, above all in maintaining long-term compliance and adherence in order to ensure clinical efficacy. Psychological therapies with diet and exercise plans could better help patients in achieving weight loss outcomes, both inside hospitals and clinical centers and during out-patient follow-up sessions. In the management of chronic diseases clinical psychology play a key role due to the need of working on psychological conditions of patients, their families and their caregivers. mHealth approach could overcome limitations linked with the traditional, restricted and highly expensive in-patient treatment of many chronic pathologies: one of the best up-to-date application is the management of obesity with type 2 diabetes, where mHealth solutions can provide remote opportunities for enhancing weight reduction and reducing complications from clinical, organizational and economic perspectives. A stepped care mHealth-based approach is an interesting perspective in chronic care management of obesity with type 2 diabetes. One promising future direction could be treating obesity, considered as a chronic multifactorial disease, using a stepped-care approach: -mhealth or traditional based lifestyle psychoeducational and nutritional approach. -health professionals-driven multidisciplinary protocols tailored for each patient. -inpatient approach with the inclusion of drug therapies and other multidisciplinary treatments. -bariatric surgery with psychological and medical follow-up In the chronic care management of globesity mhealth solutions cannot substitute traditional approaches, but they can supplement some steps in clinical psychology and medicine both for obesity prevention and for weight loss management.

Keywords: clinical health psychology, mhealth, obesity, type 2 diabetes, stepped care, chronic care management

Procedia PDF Downloads 318
337 The Effect of Swirl on the Flow Distribution in Automotive Exhaust Catalysts

Authors: Piotr J. Skusiewicz, Johnathan Saul, Ijhar Rusli, Svetlana Aleksandrova, Stephen. F. Benjamin, Miroslaw Gall, Steve Pierson, Carol A. Roberts

Abstract:

The application of turbocharging in automotive engines leads to swirling flow entering the catalyst. The behaviour of this type of flow within the catalyst has yet to be adequately documented. This work discusses the effect of swirling flow on the flow distribution in automotive exhaust catalysts. Compressed air supplied to a moving-block swirl generator allowed for swirling flow with variable intensities to be generated. Swirl intensities were measured at the swirl generator outlet using single-sensor hot-wire probes. The swirling flow was fed into diffusers with total angles of 10°, 30° and 180°. Downstream of the diffusers, a wash-coated diesel oxidation catalyst (DOC) of length 143.8 mm, diameter 76.2 mm and nominal cell density of 400 cpsi was fitted. Velocity profiles were measured at the outlet sleeve about 30 mm downstream of the monolith outlet using single-sensor hot-wire probes. Wall static pressure was recorded using a multi-tube manometer connected to pressure taps positioned along the diffuser walls. The results show that as swirl is increased, more of the flow is directed towards the diffuser walls. The velocity decreases around the centre-line and maximum velocities are observed close to the outer radius of the monolith for all flow rates. At the maximum swirl intensity, reversed flow was recorded near the centre of the monolith. Wall static pressure measurements in the 180° diffuser indicated no pressure recovery as the flow enters the diffuser. This is indicative of flow separation at the inlet to the diffuser. To gain insight into the flow structure, CFD simulations have been performed for the 180° diffuser for a flow rate of 63 g/s. The geometry of the model consists of the complete assembly from the upstream swirl generator to the outlet sleeve. Modelling of the flow in the monolith was achieved using the porous medium approach, where the monolith with parallel flow channels is modelled as a porous medium that resists the flow. A reasonably good agreement was achieved between the experimental and CFD results downstream of the monolith. The CFD simulations allowed visualisation of the separation zones and central toroidal recirculation zones that occur within the expansion region at certain swirl intensities which are highlighted.

Keywords: catalyst, computational fluid dynamics, diffuser, hot-wire anemometry, swirling flow

Procedia PDF Downloads 283
336 Assessment of Nuclear Medicine Radiation Protection Practices Among Radiographers and Nurses at a Small Nuclear Medicine Department in a Tertiary Hospital

Authors: Nyathi Mpumelelo; Moeng Thabiso Maria

Abstract:

BACKGROUND AND OBJECTIVES: Radiopharmaceuticals are used for diagnosis, treatment, staging and follow up of various diseases. However, there is concern that the ionizing radiation (gamma rays, α and ß particles) emitted by radiopharmaceuticals may result in exposure of radiographers and nurses with limited knowledge of the principles of radiation protection and safety, raising the risk of cancer induction. This study aimed at investigation radiation safety awareness levels among radiographers and nurses at a small tertiary hospital in South Africa. METHODS: An analytical cross-sectional study. A validated two-part questionnaire was implemented to consenting radiographers and nurses working in a Nuclear Medicine Department. Part 1 gathered demographic information (age, gender, work experience, attendance to/or passing ionizing radiation protection courses). Part 2 covered questions related to knowledge and awareness of radiation protection principles. RESULTS: Six radiographers and five nurses participated (27% males and 73% females). The mean age was 45 years (age range 20-60 years). The study revealed that neither professional development courses nor radiation protection courses are offered at the Nuclear Medicine Department understudy. However, 6/6 (100%) radiographers exhibited a high level of awareness of radiation safety principles on handling and working with radiopharmaceuticals which correlated to their years of experience. As for nurses, 4/5 (80%) showed limited knowledge and awareness of radiation protection principles irrespective of the number of years in the profession. CONCLUSION: Despite their major role of caring for patients undergoing diagnostic and therapeutic treatments, the nurses showed limited knowledge of ionizing radiation and associated side effects. This was not surprising since they never received any formal basic radiation safety course. These findings were not unique to this Centre. A study conducted in a Kuwaiti Radiology Department also established that the vast majority of nurses did not understand the risks of working with ionizing radiation. Similarly, nurses in an Australian hospital exhibited knowledge limitations. However, nursing managers did provide the necessary radiation safety training when requested. In Guatemala and Saudi Arabia, where there was shortage of professional radiographers, nurses underwent radiography training, a course that equipped them with basic radiation safety principles. The radiographers in the Centre understudy unlike others in various parts of the world demonstrated substantial knowledge and awareness on radiation protection. Radiations safety courses attended when an opportunity arose played a critical role in their awareness. The knowledge and awareness levels of these radiographers were comparable to their counterparts in Sudan. However, it was much more above that of their counterparts in Jordan, Nigeria, Nepal and Iran who were found to have limited awareness and inadequate knowledge on radiation dose. Formal radiation safety and awareness courses and workshops can play a crucial role in raising the awareness of nurses and radiographers on radiation safety for their personal benefit and that of their patients.

Keywords: radiation safety, radiation awareness, training, nuclear medicine

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335 Engineering Escherichia coli for Production of Short Chain Fatty Acid by Exploiting Fatty Acid Metabolic Pathway

Authors: Kamran Jawed, Anu Jose Mattam, Zia Fatma, Saima Wajid, Malik Z. Abdin, Syed Shams Yazdani

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Worldwide demand of natural and sustainable fuels and chemicals have encouraged researchers to develop microbial platform for synthesis of short chain fatty acids as they are useful precursors to replace petroleum-based fuels and chemicals. In this study, we evaluated the role of fatty acid synthesis and β-oxidation cycle of Escherichia coli to produce butyric acid, a 4-carbon short chain fatty acid, with the help of three thioesterases, i.e., TesAT from Anaerococcus tetradius, TesBF from Bryantella formatexigens and TesBT from Bacteroides thetaiotaomicron. We found that E. coli strain transformed with gene for TesBT and grown in presence of 8 g/L glucose produced maximum butyric acid titer at 1.46 g/L, followed by that of TesBF at 0.85 g/L and TesAT at 0.12 g/L, indicating that these thioesterases were efficiently converting short chain fatty acyl-ACP intermediate of fatty acid synthesis pathway into the corresponding acid. The titer of butyric acid varied significantly depending upon the plasmid copy number and strain genotype. Deletion of genes for fatty acyl-CoA synthetase and acyl-CoA dehydrogenase, which are involved in initiating the fatty acid degradation cycle, and overexpression of FadR, which is a dual transcriptional regulator and exerts negative control over fatty acid degradation pathway, reduced up to 30% of butyric acid titer. This observation suggested that β-oxidation pathway is working synergistically with fatty acid synthesis pathway in production of butyric acid. Moreover, accelerating the fatty acid elongation cycle by overexpressing acetyl-CoA carboxyltransferase (Acc) and 3-hydroxy-acyl-ACP dehydratase (FabZ) or by deleting FabR, the transcription suppressor of elongation, did not improve the butyric acid titer, rather favored the long chain fatty acid production. Finally, a balance between cell growth and butyric acid production was achieved with the use of phosphorous limited growth medium and 14.3 g/L butyric acid, and 17.5 g/L total free fatty acids (FFAs) titer was achieved during fed-batch cultivation. We have engineered an E. coli strain which utilizes the intermediate of both fatty acid synthesis and degradation pathway, i.e. butyryl-ACP and -CoA, to produce butyric acid from glucose. The strategy used in this study resulted in highest reported titers of butyric acid and FFAs in engineered E. coli.

Keywords: butenoic acid, butyric acid, Escherichia coli, fed-batch fermentation, short chain fatty acids, thioesterase

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334 Knowledge, Attitude, and Practice of Physical Activity among Adults in Alimosho Local Government Area

Authors: Elizabeth Adebomi Akinlotan, Olukemi Odukoya

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INTRODUCTION: Physical Activity is defined as activity that involves bodily movement which is done as a part of daily activity in the form of working, playing, active transportation such as walking and also as a form of recreational activity. Physical inactivity has been identified as the fourth leading risk factor for global mortality and morbidity causing an estimated 3.2 million deaths globally and 5.5% of total deaths and it remains a pressing public health issue. There is a shift in the major causes of death from communicable to non-communicable diseases in many developed countries and this is fast becoming the case in developing countries. Physical activity is an important determinant of health and has been associated with lower mortality rates as it reduces the risk of developing chronic diseases such as diabetes mellitus, hypertension, stroke, cancer and osteoporosis. It improves musculoskeletal health, controls weight and reduces symptoms of depression. AIM: The aim is to study the knowledge, attitude and practices of physical activity among adults in Alimosho local government area. METHODOLOGY: This was a descriptive cross sectional survey designed to study the knowledge, attitude and practice of physical activity among adults in Alimosho Local Government Area. The study population were 250 adults aged 18-65 who were residents of the area of more than 6 months duration and had no chronic disease condition or physical disability. A multistage sampling method was used to select the respondents and data was collected using interviewer administered questionnaires. The data was analyzed with the use of EPI-info 2007 statistical software. Chi Square was thereafter used to test the association between selected variables. The level of statistical significance was set at 5% (p<0.05). RESULTS: In general, majority (61.6%) of the respondents had a good knowledge of what physical activity entails, 34.0% had fair knowledge and 4.4% had poor knowledge. There was a favorable attitude towards physical activity among the respondents with 82.4% having an overall positive attitude. Below a third of the respondents (26.4%) reported having a high physical activity (METS > 3001) while 40.0% had moderate (601-3000 METS) levels of activity and 33.6% were inactive (<600METS). There is statistical significance between the gender of the respondent and the levels of physical activity (p=0.0007); 75.2% males reached the minimum recommendations while 24.8% were inactive and 55.0% females reached the minimum recommendations while 45.0% were inactive. Results also showed that of 95 respondents who were satisfied with their levels of physical activity, 33.7% were insufficiently active while 66.3% were either minimally active or highly active and of 110 who were unsatisfied with their levels of physical activity, 72.0% were above the minimum recommendations while 38.0% were insufficiently active. CONCLUSION: In contrast to the high level of knowledge and favorable attitude towards physical activity, there was a lower level of practice of high or moderate physical activities. It is recommended that more awareness should be created on the recommended levels of physical activity especially for the vigorous intensity and moderate intensity physical activity.

Keywords: METS, physical activity, physical inactivity, public health

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333 Dexamethasone Treatment Deregulates Proteoglycans Expression in Normal Brain Tissue

Authors: A. Y. Tsidulko, T. M. Pankova, E. V. Grigorieva

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High-grade gliomas are the most frequent and most aggressive brain tumors which are characterized by active invasion of tumor cells into the surrounding brain tissue, where the extracellular matrix (ECM) plays a crucial role. Disruption of ECM can be involved in anticancer drugs effectiveness, side-effects and also in tumor relapses. The anti-inflammatory agent dexamethasone is a common drug used during high-grade glioma treatment for alleviating cerebral edema. Although dexamethasone is widely used in the clinic, its effects on normal brain tissue ECM remain poorly investigated. It is known that proteoglycans (PGs) are a major component of the extracellular matrix in the central nervous system. In our work, we studied the effects of dexamethasone on the ECM proteoglycans (syndecan-1, glypican-1, perlecan, versican, brevican, NG2, decorin, biglican, lumican) using RT-PCR in the experimental animal model. It was shown that proteoglycans in rat brain have age-specific expression patterns. In early post-natal rat brain (8 days old rat pups) overall PGs expression was quite high and mainly expressed PGs were biglycan, decorin, and syndecan-1. The overall transcriptional activity of PGs in adult rat brain is 1.5-fold decreased compared to post-natal brain. The expression pattern was changed as well with biglycan, decorin, syndecan-1, glypican-1 and brevican becoming almost equally expressed. PGs expression patterns create a specific tissue microenvironment that differs in developing and adult brain. Dexamethasone regimen close to the one used in the clinic during high-grade glioma treatment significantly affects proteoglycans expression. It was shown that overall PGs transcription activity is 1.5-2-folds increased after dexamethasone treatment. The most up-regulated PGs were biglycan, decorin, and lumican. The PGs expression pattern in adult brain changed after treatment becoming quite close to the expression pattern in developing brain. It is known that microenvironment in developing tissues promotes cells proliferation while in adult tissues proliferation is usually suppressed. The changes occurring in the adult brain after dexamethasone treatment may lead to re-activation of cell proliferation due to signals from changed microenvironment. Taken together obtained data show that dexamethasone treatment significantly affects the normal brain ECM, creating the appropriate microenvironment for tumor cells proliferation and thus can reduce the effectiveness of anticancer treatment and promote tumor relapses. This work has been supported by a Russian Science Foundation (RSF Grant 16-15-10243)

Keywords: dexamthasone, extracellular matrix, glioma, proteoglycan

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332 Constitutive Androstane Receptor (CAR) Inhibitor CINPA1 as a Tool to Understand CAR Structure and Function

Authors: Milu T. Cherian, Sergio C. Chai, Morgan A. Casal, Taosheng Chen

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This study aims to use CINPA1, a recently discovered small-molecule inhibitor of the xenobiotic receptor CAR (constitutive androstane receptor) for understanding the binding modes of CAR and to guide CAR-mediated gene expression profiling studies in human primary hepatocytes. CAR and PXR are xenobiotic sensors that respond to drugs and endobiotics by modulating the expression of metabolic genes that enhance detoxification and elimination. Elevated levels of drug metabolizing enzymes and efflux transporters resulting from CAR activation promote the elimination of chemotherapeutic agents leading to reduced therapeutic effectiveness. Multidrug resistance in tumors after chemotherapy could be associated with errant CAR activity, as shown in the case of neuroblastoma. CAR inhibitors used in combination with existing chemotherapeutics could be utilized to attenuate multidrug resistance and resensitize chemo-resistant cancer cells. CAR and PXR have many overlapping modulating ligands as well as many overlapping target genes which confounded attempts to understand and regulate receptor-specific activity. Through a directed screening approach we previously identified a new CAR inhibitor, CINPA1, which is novel in its ability to inhibit CAR function without activating PXR. The cellular mechanisms by which CINPA1 inhibits CAR function were also extensively examined along with its pharmacokinetic properties. CINPA1 binding was shown to change CAR-coregulator interactions as well as modify CAR recruitment at DNA response elements of regulated genes. CINPA1 was shown to be broken down in the liver to form two, mostly inactive, metabolites. The structure-activity differences of CINPA1 and its metabolites were used to guide computational modeling using the CAR-LBD structure. To rationalize how ligand binding may lead to different CAR pharmacology, an analysis of the docked poses of human CAR bound to CITCO (a CAR activator) vs. CINPA1 or the metabolites was conducted. From our modeling, strong hydrogen bonding of CINPA1 with N165 and H203 in the CAR-LBD was predicted. These residues were validated to be important for CINPA1 binding using single amino-acid CAR mutants in a CAR-mediated functional reporter assay. Also predicted were residues making key hydrophobic interactions with CINPA1 but not the inactive metabolites. Some of these hydrophobic amino acids were also identified and additionally, the differential coregulator interactions of these mutants were determined in mammalian two-hybrid systems. CINPA1 represents an excellent starting point for future optimization into highly relevant probe molecules to study the function of the CAR receptor in normal- and pathophysiology, and possible development of therapeutics (for e.g. use for resensitizing chemoresistant neuroblastoma cells).

Keywords: antagonist, chemoresistance, constitutive androstane receptor (CAR), multi-drug resistance, structure activity relationship (SAR), xenobiotic resistance

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