Search results for: complete blood count

Authors: Chengcao Sun, Cuili Yang, Shujun Li, Ruilin Xue, Liang Wang, Yongyong Xi, Dejia Li

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Backgrounds: Sulforaphane, one of the most important isothiocyanates in the human diet, is known to have chemopreventive and antioxidant activities in different tissues via activation of NF-E2-related factor 2 (Nrf2)-mediated induction of antioxidant/phase II enzymes, such as heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). However, its effects on muscular dystrophy remain unknown. This work was undertaken to evaluate the effects of Sulforaphane on Duchenne muscular dystrophy (DMD). Methods: 4-week-old mdx mice were treated with SFN by gavage (2 mg/kg body weight per day) for 8 weeks. Blood was collected from eye socket every week, and tibial anterior, extensor digitorum longus, gastrocnemius, soleus, triceps brachii muscles and heart samples were collected after 8-week gavage. Force measurements and mice exercise capacity assays were detected. GSH/GSSG ratio, TBARS, CK and LDH levels were analyzed by spectrophotometric methods. H&E staining was used to analyze histological and morphometric of skeletal muscles of mdx mice, and Evas blue dye staining was made to detect sarcolemmal integrity of mdx mice. Further, the role of Sulforaphane on Nrf2/ARE signaling pathway was analyzed by ELISA, western blot and qRT-PCR. Results: Our results demonstrated that SFN treatment increased the expression and activity of muscle phase II enzymes NQO1 and HO-1 with Nrf2 dependent manner. SFN significantly increased skeletal muscle mass, muscle force (~30%), running distance (~20%) and GSH/GSSG ratio (~3.2 folds) of mdx mice, and decreased the activities of plasma creatine phosphokinase (CK) (~45%) and lactate dehydrogenase (LDH) (~40%), gastrocnemius hypertrophy (~25%), myocardial hypertrophy (~20%) and MDA levels (~60%). Further, SFN treatment also reduced the central nucleation (~40%), fiber size variability, inflammation and improved the sarcolemmal integrity of mdx mice. Conclusions: Collectively, these results show that SFN can improve muscle function, pathology and protect dystrophic muscle from oxidative damage in mdx mice through Nrf2 signaling pathway, which indicate Nrf2 may have clinical implications for the treatment of patients with muscular dystrophy.

Keywords: sulforaphane, duchenne muscular dystrophy, Nrf2, oxidative stress

Procedia PDF Downloads 323

Authors: Mohamed M. Ibrahim, Gaber A. M. Mersal, Salih Al-Juaid, Samir A. El-Shazly

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A series of mixed ligand complexes, viz., [Cu(BPy)(Gly)X]Y {X = Cl (1), Y = 0; X = 0, Y = ClO4- (2); X = H2O, Y = NO3- (3); X = H2O, Y = CH3COO- (4); and [Cu(BPy)(Gly)-(H2O)]2(SO4) (5) have been synthesized. Their structures and properties were characterized by elemental analysis, thermal analaysis, IR, UV–vis, and ESR spectroscopy, as well as electrochemical measurements including cyclic voltammetry, electrical molar conductivity, and magnetic moment measurements. Complexes 1 and 2 formed slightly distorted square-pyramidal coordination geometries of CuN3OCl and CuN3O2, respectively in which the N,O-donor glycine and N,N-donor bipyridyl bind at the basal plane with chloride ion or water as the axial ligand. Complex 3 shows square planar CuN3O coordination geometry, which exhibits chemically significant hydrogen bonding interactions besides showing coordination polymer formation. The superoxide dismutase and catalase-like activities of all complexes were tested and were found to be promising candidates as durable electron-transfer catalyst being close to the efficiency of the mimicking enzymes displaying either catalase or tyrosinase activity to serve for complete reactive oxygen species (ROS) detoxification, both with respect to superoxide radicals and related peroxides. The DNA binding interaction with super coiled pGEM-T plasmid DNA was investigated by using spectral (absorption and emission) titration and electrochemical techniques. The results revealed that DNA intercalate with complexes 1 and 2 through the groove binding mode. The calculated intrinsic binding constant (Kb) of 1 and 2 were 4.71 and 2.429 × 105 M−1, respectively. Gel electrophoresis study reveals the fact that both complexes cleave super coiled pGEM-T plasmid DNA to nicked and linear forms in the absence of any additives. On the other hand, the interaction of both complexes with DNA, the quasi-reversible CuII/CuI redox couple slightly improves its reversibility with considerable decrease in current intensity. All the experimental results indicate that the bipyridyl mixed copper(II) complex (1) intercalate more effectively into the DNA base pairs.

Keywords: enzyme mimics, mixed ligand complexes, X-ray structures, antioxidant, DNA-binding, DNA cleavage

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Authors: Sreejith Jayachandran, Mojtaba Ghods, Morteza Mohammadzaheri

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The modern busy world is running behind new embedded technologies based on computers and software; meanwhile, some people forget to do their health condition and regular medical check-ups. Some of them postpone medical check-ups due to a lack of time and convenience, while others skip these regular evaluations and medical examinations due to huge medical bills and hospital expenses. Engineers and medical experts have come together to give birth to a new device in the telemonitoring system capable of monitoring, checking, and evaluating the health status of the human body remotely through the internet for the needs of all kinds of people. The remote health monitoring device is a microcontroller-based embedded unit. Various types of sensors in this device are connected to the human body, and with the help of an Arduino UNO board, the required analogue data is collected from the sensors. The microcontroller on the Arduino board processes the analogue data collected in this way into digital data and transfers that information to the cloud, and stores it there, and the processed digital data is instantly displayed through the LCD attached to the machine. By accessing the cloud storage with a username and password, the concerned person’s health care teams/doctors and other health staff can collect this data for the assessment and follow-up of that patient. Besides that, the family members/guardians can use and evaluate this data for awareness of the patient's current health status. Moreover, the system is connected to a Global Positioning System (GPS) module. In emergencies, the concerned team can position the patient or the person with this device. The setup continuously evaluates and transfers the data to the cloud, and also the user can prefix a normal value range for the evaluation. For example, the blood pressure normal value is universally prefixed between 80/120 mmHg. Similarly, the RHMS is also allowed to fix the range of values referred to as normal coefficients. This IoT-based miniature system (11×10×10) cm³ with a low weight of 500 gr only consumes 10 mW. This smart monitoring system is manufactured with 100 GBP, which can be used not only for health systems, it can be used for numerous other uses including aerospace and transportation sections.

Keywords: embedded technology, telemonitoring system, microcontroller, Arduino UNO, cloud storage, global positioning system, remote health monitoring system, alert system

Procedia PDF Downloads 90

Authors: Ardiana Murtezani, Ilirijana Dallku, Teuta Osmani Vllasolli, Sabit Sllamniku

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Background: The use of foot orthoses are always indicated when there are alterations of the optimal biomechanics' position of the foot. Orthotics are very effective and very suitable for the majority of patients with pain due to overload which can be related to biomechanical disorders. Aim: To assess the frequency of patients requiring foot orthoses, type of orthoses and analysis of their disease leading to the use of foot orthoses. Material and Methods: Our study included 128 patients with various foot pathologies, treated at the outpatient department of the Ortho-Prosthetic Center of Kosovo (OPCK) in Prishtina. Prospective-descriptive clinical method was used during this study. Functional status of patients was examined, and the following parameters are noted: range of motion measurements for the affected joints/lower extremities, manual test for muscular strength below the knee and foot of the affected extremity, perimeter measurements of the lower extremities, measurements of lower extremities, foot length measurement, foot width measurements and size. In order to complete the measurements the following instruments are used: plantogram, pedogram, meter and cork shoe lift appliances. Results: The majority of subjects in this study are male (60.2% vs. 39.8%), and the dominant age group was 0-9 (47.7%), 61 subjects respectively. Most frequent foot disorders were: congenital disease 60.1%, trauma cases 13.3%, consequences from rheumatologic disease 12.5%, neurologic dysfunctions 11.7%, and the less frequented are the infectious cases 1.6%. Congenital anomalies were the most frequent cases, and from this group majority of cases suffered from pes planovalgus (37.5%), eqinovarus (15.6%) and discrepancies between extremities (6.3%). Furthermore, traumatic amputations (2.3%) and arthritis (0.8%). As far as neurologic disease, subjects with cerebral palsy are represented with (3.1%), peroneal nerve palsy (2.3%) and hemiparesis (1.6%). Infectious disease osteomyelitis sequels are represented with (1.6%). Conclusion: Based on our study results, we have concluded that the use of foot orthoses for patients suffering from rheumatoid arthritis and nonspecific arthropaty was effective treatment choice, leading to decrease of pain, less deformities and improves the quality of life.

Keywords: orthoses, epidemiological analysis, rheumatoid arthritis, rehabilitation

Procedia PDF Downloads 232

Authors: Asma'u Mahe, Abdullahi A. Imam, Adamu J. Alhassan, Nasiru Abdullahi, Sadiya A. Bichi, Nura Lawal, Kamaluddeen Babagana

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Malaria is a disease with global health significance. It is caused by parasites and transmitted by Anopheles mosquitoes. Increase in insecticide resistance threatens the disease vector control. The strength of selection pressure acting on a mosquito population in relation to insecticide resistance can be assess by determining the genetic diversity of a fragment spanning exon- 20 of IIS6 of the voltage gated sodium channel (VGSC). Larval samples reared to adulthood were identified and kdr (knock down resistance) profile was determined. The DNA sequences were used to assess the patterns of genetic differentiation by determining the levels of genetic variability between the Anopheles mosquitoes. Genetic differentiation of the Anopheles mosquitoes based on a portion of the voltage gated sodium channel gene was obtained. Polymorphisms were detected; sequence variation and analysis were presented as a phylogenetic tree. Phylogenetic tree of VGSC haplotypes was constructed for samples of the Anopheles mosquitoes using the maximum likelihood method in MEGA 6.0 software. DNA sequences were edited using BioEdit sequence editor. The edited sequences were aligned with reference sequence (Kisumu strain). Analyses were performed as contained in dnaSP 5.10. Results of genetic parameters of polymorphism and haplotype reconstruction were presented in count. Twenty sequences were used for the analysis. Regions selected were 1- 576, invariable (monomorphic) sites were 460 while variable (polymorphic) sites were 5 giving the number of total mutations observed in this study. Mutations obtained from the study were at codon 105: TTC- Phenylalanine replaces TCC- Serine, codon 513: TAG- Termination replaces TTG- Leucine, codon 153, 300 and 553 mutations were non-synonymous. From the constructed phylogenetic tree, some groups were shown to be closer with Exon20Gambiae Kisumu (Reference strain) having some genetic distance, while 5-Exon20Gambiae-F I13.ab1, 18-Exon20Gambiae-F C17.ab1, and 2-Exon20Gambiae-F C13.ab1 clustered together genetically differentiated away from others. Mutations observed in this study can be attributed to the high insecticide resistance profile recorded in the study areas. Haplotype networks of pattern of genetic variability and polymorphism for the fragment of the VGSC sequences of sampled Anopheles mosquitoes revealed low haplotypes for the present study. Haplotypes are set of closely linked DNA variation on X-chromosome. Haplotypes were scaled accordingly to reflect their respective frequencies. Low haplotype number, four VGSC-1014F haplotypes were observed in this study. A positive association was previously established between low haplotype number of VGSC diversity and pyrethroid resistance through kdr mechanism. Significant values at (P < 0.05) of Tajima D and Fu and Li D’ were observed for some of the results indicating possible signature of positive selection on the fragment of VGSC in the study. This is the first report of VGSC-1014F in the study site. Based on the results, the mutation was present in low frequencies. However, the roles played by the observed mutations need further investigation. Mutations, environmental factors among others can affect genetic diversity. The study area has recorded increase in insecticide resistance that can affect vector control in the area. This finding might affect the efforts made against malaria. Sequences were deposited in GenBank for Accession Number.

Keywords: anopheles mosquitoes, insecticide resistance, kdr, malaria, voltage gated sodium channel

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Authors: Subrat Partha Sarathi Pattnaik, Rajan N.K.S.

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Integrated rocket ramjet engines are highly suitable for long range missile applications. Designing the fixed geometry intakes for such missiles that can operate efficiently over a range of operating conditions is a highly challenging task. Hence, the present study aims to evaluate the effect of throat design on the performance of a rectangular mixed compression intake for operation in the Mach number range of 1.8 – 2.5. The analysis has been carried out at four different Mach numbers of 1.8, 2, 2.2, 2.5 and two angle-of-attacks of +5 and +10 degrees. For the throat design, three different throat heights have been considered, one corresponding to a 3- external shock design and two heights corresponding to a 2-external shock design leading to different internal contraction ratios. The on-design Mach number for the study is M 2.2. To obtain the viscous flow field in the intake, the theoretical designs have been considered for computational fluid dynamic analysis. For which Favre averaged Navier- Stokes (FANS) equations with two equation SST k-w model have been solved. The analysis shows that for zero angle of attack at on-design and high off-design Mach number operations the three-ramp design leads to a higher total pressure recovery (TPR) compared to the two-ramp design at both contraction ratios maintaining same mass flow ratio (MFR). But at low off-design Mach numbers the total pressure shows an opposite trend that is maximum for the two-ramp low contraction ratio design due to lower shock loss across the external shocks similarly the MFR is higher for low contraction ratio design as the external ramp shocks move closer to the cowl. At both the angle of attack conditions and complete range of Mach numbers the total pressure recovery and mass flow ratios are highest for two ramp low contraction design due to lower stagnation pressure loss across the detached bow shock formed at the ramp and lower mass spillage. Hence, low contraction design is found to be suitable for higher off-design performance.

Keywords: internal contraction ratio, mass flow ratio, mixed compression intake, performance, supersonic flows

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Authors: David Serero, Loic Couton, Jean-Denis Parisse, Robert Leroy

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This paper presents an analysis method of airflow at the periphery of several typologies of architectural volumes. To understand the complexity of the urban environment on the airflows in the city, we compared three sites at different architectural scale. The research sets a method to identify the optimal location for the installation of wind turbines on the edges of a building and to achieve an improvement in the performance of energy extracted by precise localization of an accelerating wing called “aero foil”. The objective is to define principles for the installation of wind turbines and natural ventilation design of buildings. Instead of theoretical winds analysis, we combined numerical aeraulic simulations using STAR CCM + software with wind data, over long periods of time (greater than 1 year). If airflows computer fluid analysis (CFD) simulation of buildings are current, we have calibrated a virtual wind tunnel with wind data using in situ anemometers (to establish localized cartography of urban winds). We can then develop a complete volumetric model of the behavior of the wind on a roof area, or an entire urban island. With this method, we can categorize: - the different types of wind in urban areas and identify the minimum and maximum wind spectrum, - select the type of harvesting devices - fixing to the roof of a building, - the altimetry of the device in relation to the levels of the roofs - The potential nuisances around. This study is carried out from the recovery of a geolocated data flow, and the connection of this information with the technical specifications of wind turbines, their energy performance and their speed of engagement. Thanks to this method, we can thus define the characteristics of wind turbines to maximize their performance in urban sites and in a turbulent airflow regime. We also study the installation of a wind accelerator associated with buildings. The “aerofoils which are integrated are improvement to control the speed of the air, to orientate it on the wind turbine, to accelerate it and to hide, thanks to its profile, the device on the roof of the building.

Keywords: wind energy harvesting, wind turbine selection, urban wind potential analysis, CFD simulation for architectural design

Procedia PDF Downloads 151

Authors: Arpit Kumar Shrivastava, Subrat Kumar, Rajani Kanta Mohapatra, Priyadarshi Soumyaranjan Sahu

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Computational approaches to predict structure, function and other biological characteristics of proteins are becoming more common in comparison to the traditional methods in drug discovery. Cryptosporidiosis is a major zoonotic diarrheal disease particularly in children, which is caused primarily by Cryptosporidium hominis and Cryptosporidium parvum. Currently, there are no vaccines for cryptosporidiosis and recommended drugs are not effective. With the availability of complete genome sequence of C. hominis, new targets have been recognized for the development of effective and better drugs and/or vaccines. We identified a unique hypothetical epitopic protein in C. hominis genome through BLASTP analysis. A 3D model of the hypothetical protein was generated using I-Tasser server through threading methodology. The quality of the model was validated through Ramachandran plot by PROCHECK server. The functional annotation of the hypothetical protein through DALI server revealed structural similarity with human Transportin 3. Phylogenetic analysis for this hypothetical protein also showed C. hominis hypothetical protein (CUV04613) was the closely related to human transportin 3 protein. The 3D protein model is further subjected to virtual screening study with inhibitors from the Zinc Database by using Dock Blaster software. Docking study reported N-(3-chlorobenzyl) ethane-1,2-diamine as the best inhibitor in terms of docking score. Docking analysis elucidated that Leu 525, Ile 526, Glu 528, Glu 529 are critical residues for ligand–receptor interactions. The molecular dynamic simulation was done to access the reliability of the binding pose of inhibitor and protein complex using GROMACS software at 10ns time point. Trajectories were analyzed at each 2.5 ns time interval, among which, H-bond with LEU-525 and GLY- 530 are significantly present in MD trajectories. Furthermore, antigenic determinants of the protein were determined with the help of DNA Star software. Our study findings showed a great potential in order to provide insights in the development of new drug(s) or vaccine(s) for control as well as prevention of cryptosporidiosis among humans and animals.

Keywords: cryptosporidium hominis, hypothetical protein, molecular docking, molecular dynamics simulation

Procedia PDF Downloads 365

Authors: Zi-Yan Liao, Shan-Yu Zhang, Ya-Xian Lin, Ya-Lun Lee, Shih-Chuan Huang, Hong-Ru Lin

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Traditional wound dressings, such as gauze, bandages, etc., are easy to adhere to the tissue fluid exuded from the wound, causing secondary damage to the wound during removal. This study takes this as the idea to develop a hydrogel dressing, to explore that the dressing will not cause secondary damage to the wound when it is torn off, and at the same time, create an environment conducive to wound healing. First, the temperature-sensitive material N-isopropylacrylamide (NIPAAm) was used as the substrate. Due to its low mechanical properties, the hydrogel would break due to pulling during human activities. Polyvinyl alcohol (PVA) interpenetrates into it to enhance the mechanical properties, and a semi-interpenetration (semi-IPN) composed of poly(N-isopropylacrylamide) (PNIPAAm) and polyvinyl alcohol (PVA) was prepared by free radical polymerization. PNIPAAm was cross-linked with N,N'-methylenebisacrylamide (NMBA) in an ice bath in the presence of linear PVA, and tetramethylhexamethylenediamine (TEMED) was added as a promoter to speed up the gel formation. The polymerization stage was carried out at 16°C for 17 hours and washed with distilled water for three days after gel formation, and the water was changed several times in the middle to complete the preparation of semi-IPN hydrogel. Finally, various tests were used to analyze the effects of different ratios of PNIPAAm and PVA on semi-IPN hydrogels. In the swelling test, it was found that the maximum swelling ratio can reach about 50% under the environment of 21°C, and the higher the ratio of PVA, the more water can be absorbed. The saturated moisture content test results show that when more PVA is added, the higher saturated water content. The water vapor transmission rate test results show that the value of the semi-IPN hydrogel is about 57 g/m²/24hr, which is not much related to the proportion of PVA. It is found in the LCST test compared with the PNIPAAm hydrogel; the semi-IPN hydrogel possesses the same critical solution temperature (30-35°C). The semi-IPN hydrogel prepared in this study has a good effect on temperature response and has the characteristics of thermal sensitivity. It is expected that after improvement, it can be used in the treatment of surface wounds, replacing the traditional dressing shortcoming.

Keywords: hydrogel, N-isopropylacrylamide, polyvinyl alcohol, hydrogel wound dressing, semi-interpenetrating polymer network

Procedia PDF Downloads 80

Authors: Sandra Pietri, Helene Dubout, Sabrina Ena, Candice Hoste, Enrico Bastianelli

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Bone Therapeutics is a bone cell therapy company addressing high unmet medical needs in the field of bone fracture repair, more specifically in non-union and delayed-union fractures where the bone repair process is impaired. The company has developed a unique allogeneic osteoblastic cell product (ALLOB®) derived from bone marrow which is currently tested in humans in the indication of delayed-union fractures. The purpose of our study was to directly compare ALLOB® vs. non-differentiated mesenchymal stem cells (MSC) for their in vitro osteogenic characteristics and their in vivo osteogenic potential in order to determine which cellular type would be the most adapted for bone fracture repair. Methods: Healthy volunteers’ bone marrow aspirates (n=6) were expended (i) into BM-MSCs using a complete MSC culture medium or (ii) into ALLOB® cells according to its manufacturing process. Cells were characterized in vitro by morphology, immunophenotype, gene expression and differentiation potential. Additionally, their osteogenic potential was assessed in vivo in the subperiosteal calvaria bone formation model in nude mice. Results: The in vitro side-by-side comparison studies showed that although ALLOB® and BM-MSC shared some common general characteristics such as the 3 minimal MSC criteria, ALLOB® expressed significantly higher levels of chondro/osteoblastic genes such as BMP2 (fold change (FC) > 100), ALPL (FC > 12), CBFA1 (FC > 3) and differentiated significantly earlier than BM-MSC toward the osteogenic lineage. Moreover the bone formation model in nude mice demonstrated that used at the same cellular concentration, ALLOB® was able to induce significantly more (160% vs.107% for control animals) bone formation than BM-MSC (118% vs. 107 % for control animals) two weeks after administration. Conclusion: Our side-by-side comparison studies demonstrated that in vitro and in vivo, ALLOB® displays superior osteogenic capacity to BM-MScs and is therefore a better candidate for the treatment of bone fractures.

Keywords: gene expression, histomorphometry, mesenchymal stem cells, osteogenic differentiation potential, preclinical

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Authors: Pampita Chakraborty, Sukumar Mukherjee

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Diabetes Mellitus (DM) is commonly encountered metabolic disorder in clinical practice. An estimated 25 percent of DM patients develop foot problems. Foot ulceration and infection are one of the major causes of morbidity, hospitalization or even amputation. Objective: To isolate and identify bacterial pathogens in Diabetic Foot Ulcer (DFU) and to observe its antimicrobial sensitivity pattern. Methodology: A prospective study was conducted for a period of 9 months at the Department of Microbiology, GD Hospital & Diabetes Institute, Kolkata. 75 DFU patients were recruited in the study. Specimens for microbiological studies obtained from ulcer base were examined as gram stained smear and was cultured aerobically on Nutrient agar, Blood agar and MacConkey agar plates. Antimicrobial sensitivity test was performed by disc diffusion techniques according to CLSI guidelines. Result: In this study out of 75cases, 73% (55/75) were male and 27% (20/75) were females with mean (SD) age of 51.11(±10) years. Out of 75 pus cultures, 63(84%) showed growth of microorganism making total of 81 bacterial isolates with 71.42% of monomicrobial infection and 28.57% of polymicrobial infection. Out of 81 isolates 53(65.43%) were gram negative and 21(25.92%) were gram positive. E.coli was relatively common isolate 21(26%) followed by Staphylococcus aureus 15(18.5%), Klebsiella pneumonia 14(17.28%), Pseudomonas aeruginosa 12 (14.81%), Proteus spp. 3 (3.70%), and Enterococcus faecalis 6 (7.40%). 75% of Gram-negative microorganism were extended Beta-lactamase enzyme (ESBL) producer and around 20 % of Klebsiella and Proteus spp. were carbapenemase enzyme producer. Among Gram positive, around 50% of S.aureus was MRSA, sensitive only to Vancomycin, Teicoplanin & Linezolid. Conclusion: More prevalence of monomicrobial gram-negative bacteria than gram-positive bacteria in DFU was observed. This study emphasizes that Beta-Lactam group of antibiotics should not be the empirical treatment of choice for Gram-negative isolates; instead alternatives like Carbapenems, Amikacin could be a better option. On the other hand, Vancomycin and Linezolid are preferred for most of the infection with gram-positive aerobes. Continuous surveillance of resistant bacteria is required for empiric therapy.

Keywords: antibiotic resistant, antimicrobial susceptibility, diabetic foot ulcer, surveillance

Procedia PDF Downloads 369

Authors: Francisco Liaño-Carrera, José Isaac Ramírez-Macías, David Salas-Monreal, Mayra Lorena Riveron-Enzastiga, Marcos Rangel-Avalos, Adriana Andrea Roldán-Ubando

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The construction of most coastal infrastructure developments around the world are usually made considering wave height, current velocities and river discharges; however, little effort has been paid to surveying sediment transport during dredging or the modification to currents outside the ports or marinas during and after the construction. This study shows a complete survey during the construction of one of the largest ports of the Gulf of Mexico. An anchored Acoustic Doppler Current Velocity profiler (ADCP), a towed ADCP and a combination of model outputs were used at the Veracruz port construction in order to describe the hourly sediment transport and current modifications in and out of the new port. Owing to the stability of the system the new port was construction inside Vergara Bay, a low wave energy system with a tidal range of up to 0.40 m. The results show a two-current system pattern within the bay. The north side of the bay has an anticyclonic gyre, while the southern part of the bay shows a cyclonic gyre. Sediment transport trajectories were made every hour using the anchored ADCP, a numerical model and the weekly data obtained from the towed ADCP within the entire bay. The sediment transport trajectories were carefully tracked since the bay is surrounded by coral reef structures which are sensitive to sedimentation rate and water turbidity. The survey shows that during dredging and rock input used to build the wave breaker sediments were locally added (< 2500 m²) and local currents disperse it in less than 4 h. While the river input located in the middle of the bay and the sewer system plant may add more than 10 times this amount during a rainy day or during the tourist season. Finally, the coastal line obtained seasonally with a drone suggests that the southern part of the bay has not been modified by the construction of the new port located in the northern part of the bay, owing to the two subsystem division of the bay.

Keywords: Acoustic Doppler Current Profiler, construction around coral reefs, dredging, port construction, sediment transport monitoring,

Procedia PDF Downloads 227

Authors: Enes Caliskan, Hatice Camgoz Akdag

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There is no doubt that humanity needs to realize the sustainability problems in the world and take serious action regarding that. All members of the United Nations adopted the 2030 Agenda for Sustainable Development, the most comprehensive study on sustainability internationally, in 2015. The summary of the study is 17 sustainable development goals. It covers everything about sustainability, such as environment, society and governance. The use of Information and Communication Technology (ICT), such as the Internet, mobile phones, and satellites, is essential for tackling the main issues facing sustainable development. Hence, the contributions of 3 major ICT companies to the sustainable development goals are assessed in this study. Quality Function Deployment (QFD) is utilized as a methodology for this study. Since QFD is an excellent instrument for comparing businesses on relevant subjects, a House of Quality must be established to complete the QFD application. In order to develop a House of Quality, the demanded qualities (voice of the customer) and quality characteristics (technical requirements) must first be determined. UN SDGs are used as demanded qualities. Quality characteristics are derived from annual sustainability and corporate social responsibility reports of ICT companies. The companies' efforts, as indicated by the QFD results, are concentrated on the use of recycled raw materials and recycling, reducing GHG emissions through energy saving and improved connectivity, decarbonizing the value chain, protecting the environment and water resources by collaborating with businesses that have completed CDP water assessments and paying attention to reducing water consumption, ethical business practices, and reducing inequality. The evaluations of the three businesses are found to be very similar when they are compared. The small differences between the companies are usually about the region they serve. Efforts made by the companies mostly concentrate on responsible consumption and production, life below water, climate action, and sustainable cities and community goals. These efforts include improving connectivity in needed areas for providing access to information, education and healthcare.

Keywords: multi-criteria decision-making, sustainable supply chain risk, supply chain agility, quality function deployment, Sustainable development goals

Procedia PDF Downloads 49

Authors: Abenezer Nigussie

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Strategic control practice is a critical exercise, as it provides a sturdy influence towards firms or production partners to achieve the full implementation of effective predetermined plans. The importance of strategic control in a company is often measured by observing the relationship between strategic management and organizational performance. The conventional philosophy of strategic control in academia and the industry places significant emphasis on the ability to plan and execute initiatives. In contrast, the same emphasis on strategic management has received less attention in the housing industry. Although the pressures of project performance can often obscure the wider social, economic, and professional context in which strategic management is undertaken, it is these broad contextual areas that make strategic control a vital issue for construction businesses. Rapidly changing social and technological issues are creating an informed environment that will appear very different in the coming decades from what is experienced in today’s companies. Construction project activity is not adequately led by strategic management tools; projects are mostly executed through simple plans and schedules. The issues that this thesis addresses and solves involve the successful accompaniment of the construction project process through these strategic management tools. The second important aspect is an evaluation of project activity, which is mostly done through simple economic and technical valuation. However, during this research, effective strategic management tools are evaluated and suggested for the assessment of project activities. The research introduces a study of the current strategic management practices of construction companies and also presents the concept of strategic management and the areas that companies need to address to compete in the global market. A summary of an industry survey is documented along with the historical research that prompted the investigation of these topics with a focus on the implementation of tools. Strategic management is a concept that concerns making decisions and taking corrective actions to achieve the future goals and objectives of a company. The objective of this paper is to review the practice of strategic management in construction companies. Questionnaires were distributed to major construction companies listed under categories of each project capable of specifying the complete expression of strategic management tools. Findings of the research showed that the majority of development companies practice strategic management tools in the process and implementation of each tool.

Keywords: strategic management, management, analysis, project management

Procedia PDF Downloads 67

Authors: Yung-Chih Kuo, Yung-I Lou

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Cationic solid lipid nanoparticles (CSLNs) with anti-melanotransferrin (AMT) and apolipoprotein E (ApoE) were used to carry antimitotic doxorubicin (Dox) across the blood–brain barrier (BBB) for glioblastoma multiforme (GBM) treatment. Dox-loaded CSLNs were prepared in microemulsion, grafted covalently with AMT and ApoE, and applied to human brain microvascular endothelial cells (HBMECs), human astrocytes, and U87MG cells. Experimental results revealed that an increase in the weight percentage of stearyl amine (SA) from 0% to 20% increased the size of AMT-ApoE-Dox-CSLNs. In addition, an increase in the stirring rate from 150 rpm to 450 rpm decreased the size of AMT-ApoE-Dox-CSLNs. An increase in the weight percentage of SA from 0% to 20% enhanced the zeta potential of AMT-ApoE-Dox-CSLNs. Moreover, an increase in the stirring rate from 150 rpm to 450 rpm reduced the zeta potential of AMT-ApoE-Dox-CSLNs. AMT-ApoE-Dox-CSLNs exhibited a spheroid-like geometry, a minor irregular boundary deviating from spheroid, and a somewhat distorted surface with a few zigzags and sharp angles. The encapsulation efficiency of Dox in CSLNs decreased with increasing weight percentage of Dox and the order in the encapsulation efficiency of Dox was 10% SA > 20% SA > 0% SA. However, the reverse order was true for the release rate of Dox, suggesting that AMT-ApoE-Dox-CSLNs containing 10% SA had better-sustained release characteristics. An increase in the concentration of AMT from 2.5 to 7.5 μg/mL slightly decreased the grafting efficiency of AMT and an increase in that from 7.5 to 10 μg/mL significantly decreased the grafting efficiency. Furthermore, an increase in the concentration of ApoE from 2.5 to 5 μg/mL slightly reduced the grafting efficiency of ApoE and an increase in that from 5 to 10 μg/mL significantly reduced the grafting efficiency. Also, AMT-ApoE-Dox-CSLNs at 10 μg/mL of ApoE could slightly reduce the transendothelial electrical resistance (TEER) and increase the permeability of propidium iodide (PI). An incorporation of 10 μg/mL of ApoE could reduce the TEER and increase the permeability of PI. AMT-ApoE-Dox-CSLNs at 10 μg/mL of AMT and 5-10 μg/mL of ApoE could significantly enhance the permeability of Dox across the BBB. AMT-ApoE-Dox-CSLNs did not induce serious cytotoxicity to HBMECs. The viability of HBMECs was in the following order: AMT-ApoE-Dox-CSLNs = AMT-Dox-CSLNs = Dox-CSLNs > Dox. The order in the efficacy of inhibiting U87MG cells was AMT-ApoE-Dox-CSLNs > AMT-Dox-CSLNs > Dox-CSLNs > Dox. A surface modification of AMT and ApoE could promote the delivery of AMT-ApoE-Dox-CSLNs to cross the BBB via melanotransferrin and low density lipoprotein receptor. Thus, AMT-ApoE-Dox-CSLNs have appropriate physicochemical properties and can be a potential colloidal delivery system for brain tumor chemotherapy.

Keywords: anti-melanotransferrin, apolipoprotein E, cationic catanionic solid lipid nanoparticle, doxorubicin, U87MG cells

Procedia PDF Downloads 284

Authors: Ade O. Oyewole, Sunday O. Okoh, Ruth O. Ishola, Adenike D. Odusote, Chima C. Igwe, Gloria N. Elemo, Anthony I. Okoh

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Azadirachta indica (Neem tree) also referred to as an all-purpose tree is used in a wide range of medical preparations in tropical and subtropical countries for prevention and management of various livestock, crops products and human diseases. In Nigeria however, the potentials of this plant have not been fully exploited thus it causes an environmental nuisance during the fruiting season. With a rise in the demand for herbal personal care products globally extracts from different parts of the neem plant were used as the bio-active ingredients in the formulation of personal care products. In this study, formulated neem soap, body cream, lotion, toothpaste and shampoo are analyzed to determine their antibacterial, antifungal, and toxicity properties. The efficacies of these products for management of infectious diseases, both oral and dermal, were also investigated in vitro. Oil from the neem seeds obtained using a mechanical press and acetone extracts of both the neem bark and leaves obtained by the maceration method were used in the formulation and production of the neem personal care products. The antimicrobial and toxicity properties of these products were investigated by agar diffusion, and haemolytic methods respectively. The five neem products (NPs) exhibited strong antibacterial activities against four multi–drug resistant pathogenic and three none pathogenic bacterial strains (Escherichia coli (180), Listeria ivanovii, Staphylococcus aureus, Enterobacter cloacae, Vibro spp., Streptococcus uberis, Mycobacterium smegmatis), except the neem lotion with insignificant activity against E. coli and S. aureus. The minimum inhibitory concentration (MIC) range was between 0.20-0.40 mg/ mL. The 5 NPs demonstrated moderate activity against three clinical dermatophytes isolates (Tinea corporis, Tinea capitis, and Tinea cruiz) as well as one fungal strain (Candida albican) with the MIC ranging between 0.30 - 0.50 mg/ mL and 0.550 mg/mL respectively. The soap and shampoo were the most active against test bacteria and fungi. The haemolytic analysis results on the 5 NPs indicated none toxicity at 0.50 mg/ mL in sheep red blood cells (SRBC).

Keywords: antimicrobial, Azadirachta indica, multi–drug resistant pathogenic bacteria, personal care products

Procedia PDF Downloads 270

Authors: Zdzislaw Kaminski, Zbigniew Czyz, Tytus Tulwin

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This paper describes the geometrical model, algorithm and CFD simulation of an airflow around a Vertical Axis Wind Turbine rotor. A solver, ANSYS Fluent, was applied for the numerical simulation. Numerical simulation, unlike experiments, enables us to validate project assumptions when it is designed to avoid a costly preparation of a model or a prototype for a bench test. This research focuses on the rotor designed according to patent no PL 219985 with its blades capable of modifying their working surfaces, i.e. absorbing wind kinetic energy. The operation of this rotor is based on a regulation of blade angle α between the top and bottom parts of blades mounted on an axis. If angle α increases, the working surface which absorbs wind kinetic energy also increases. CFD calculations enable us to compare aerodynamic characteristics of forces acting on rotor working surfaces and specify rotor operation parameters like torque or turbine assembly power output. This paper is part of the research to improve an efficiency of a rotor assembly and it contains investigation of the impact of a blade angle of wind turbine working blades on the power output as a function of rotor torque, specific rotational speed and wind speed. The simulation was made for wind speeds ranging from 3.4 m/s to 6.2 m/s and blade angles of 30°, 60°, 90°. The simulation enables us to create a mathematical model to describe how aerodynamic forces acting each of the blade of the studied rotor are generated. Also, the simulation results are compared with the wind tunnel ones. This investigation enables us to estimate the growth in turbine power output if a blade angle changes. The regulation of blade angle α enables a smooth change in turbine rotor power, which is a kind of safety measures if the wind is strong. Decreasing blade angle α reduces the risk of damaging or destroying a turbine that is still in operation and there is no complete rotor braking as it is in other Horizontal Axis Wind Turbines. This work has been financed by the Polish Ministry of Science and Higher Education.

Keywords: computational fluid dynamics, mathematical model, numerical analysis, power, renewable energy, wind turbine

Procedia PDF Downloads 337

Authors: Junaid Mahmood Alam, Sana Anwar, Sarah Sughra Asghar

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Chronic hepatitis or Hepatitis C viral (HCV) infection has been identified as one of the factors that could elicit autoimmune disease resulting in the development of auto-antibodies. Furthermore, HCV is implicated in contravening of forbearance to antigens, therefore, inciting auto-reactivity. In this regard, several near and past studies noted the prevalence of thyroid dysfunction and production of anti-thyroid antibodies (ATAb) such as anti-thyroid peroxidase (AntiTPO) and anti-thyroglobulin (AntiTG) in patients with HCV. Likewise, one of the etiologies of augmentation of thyroid disease is basically interferon therapy for HCV infections, for which a number of autoimmune diseases have been noted including Grave’s disease, Hishimoto thyroiditis. A prospectively case-control study was therefore carried out at department of clinical biochemistry lab services and chemical pathology in collaboration with department of clinical microbiology, at Liaquat National Hospital and Medical College, Karachi Pakistan for the period January 2015 to December 2017. Two control groups were inducted for comparison purpose, control group 1 = without HCV infection and with thyroid disorders (n = 20), control group 2 = with HCV infection and without thyroid disorders (n = 20), whereas HCV infected were n = 40 where more than half were noted to be positive for either of HCV IgG and Ag. In HCV group, patients with existing sub-clinical hypothyroidism and clinical hyperthyroidism were less than 5%. Analysis showed the presence of AntiTG in 12 HCV patients (30%), AntiTPO in 15 (37.5%) and both AntiTG and antiTPO in 10 patients (25%). Only 3 patients were found with the history of anti-thyroid auto-antibodies (7.5%) and one with parents and relatives with auto-immune disorders (2.5%). Patients that remained untreated were 12 (30%), under treatment 18 (45%) and with complete-course of treatment 10 (25%). As per review of the literature, meta-analysis of evident data and cross-sectional studies of selective cohorts (as studied in presented research), thyroid connection is designated as one of the most recurrent endocrine ailment associated with chronic HCV infection. Moreover, it also represents an extrahepatic disease in the continuum of HCV syndrome. In conclusion, HCV patients were more likely to encompass thyroid disorders especially related to development of either of ATAb or both antiTG and AntiTPO.

Keywords: Hepatitis C viral (HCV) infection, anti-thyroid antibodies, anti-thyroid peroxidase antibodies, anti-thyroglobulin antibodies

Procedia PDF Downloads 157

Authors: Song Hung Chi, Lee Chun Benn

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Follow by the “A Research on Types of Settlement Housing Alterations of Chinese New Village in Malaysia- A Study in Ampang New Village, Selangor” preliminary informed that the main factors for expansion and enlargement suitably due to the needs of user's life and restoration purpose. The alterations behavior generally derived at the rear position of main house with different types of derivatives, the averages expansion area are not exceeding of 100㎡, while building materials used were wooden, wooden structure, and zinc which are non-permanent building materials. Therefore, a subsequent studies taken in this paper, further to analyze the drawing with summarize method, to explore the derived forms and the constituted rules of housing alterations in Ampang Village, as a more complete presentation of housing alterations in New Village. Firstly, classified the existing housing alterations into three types by using summarize method, which are Type 1, Additional of Prototype House; Type 2, Expansion of Prototype House; and Type 3, Diffusion of Additional. The results shows that the derivative mode of alterations can be divided into the use of "continuous wall" or "non-continuous wall," this will affects the structural systems and roof styles of alterations, and formed the different layers of interior space with "stages" and "continuity". On the aspects of spatial distribution, sacrificial area as a prescriptive function of space, it was mostly remains in the original location which in the center of living area after alterations. It is an important characteristic in a New Village house, reflecting the traditional Ethics of Hakka Chinese communities in the settlement. In addition, wooden as the main building materials of constituted rules for the prototype house, although there were appeared other building materials, such as cement, brick, glass, metal and zinc after alterations, but still mostly as "wooden house" pattern. Result show because of the economy of village does not significantly improve, and also forming the similarity types in alterations and constructions of the additional building with the existing. It did not significantly improve on the quality of living, but only increased the area of usage space.

Keywords: Ampang new village, derived forms, constituted rules, alterations

Procedia PDF Downloads 320

Authors: Kittitara Chunlakittiphan, Patompong Satapornpong

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Introduction: The variation of genetics affects how our body responds to pharmaceuticals elucidates the correlation between long-term use of medical cannabis and adverse drug reactions (ADRs). Medical cannabis is regarded as the treatment for chronic pain, cancer pain, acute pain, psychological disorders, multiple sclerosis and migraine management. However, previous studies have shown that delta-9-Tetrahydrocannabinol (THC), an ingredient found in cannabis, was the cause of ADRs in CB1 receptors found in humans. Previous research suggests that distributions of the cannabinoid type 1 (CB1) receptor gene and pharmacogenetic markers, which vary amongst different populations, might affect incidences of ADRs. Although there is an evident need to investigate the level of the CB1 receptor gene (rs806365), studies on the distribution of CB1-pharmacogenetics markers in Thai patients are limited. Objective: Therefore, the aim of this study is to investigate the distribution of the rs806365 polymorphism in Thai patients who have been treated with medical cannabis. Materials and Methods: We enrolled 31 Thai patients with THC-induced ADRs and 34 THC-tolerant controls to take part in this study. All patients with THC-induced ADRs were accessed through a review of medical records by physicians. EDTA blood of 3ml was collected to obtain the CNR1 gene (rs806365) and genotyping of this gene was conducted using the real-time PCR ViiA7 (ABI, Foster City, CA, USA) following the manufacturer’s instruction. Results: The sample consisted of 65 patients (40/61.54%) were females and (25/38.46%) were males, with an age range of 19-87 years, who have been treated with medical cannabis. In this study, the most common THC-induced ADRs were dry mouth and/or dry throat, tachycardia, nausea, and arrhythmia. Across the whole sample, we found that 52.31% of Thai patients carried a heterozygous variant (rs806365, CT allele). Moreover, the number of rs806365 (CC, homozygous variant) carriers totaled seventeen people (26.15%) amongst the subjects of Thai patients treated with medical cannabis. Furthermore, 17 out of 22 patients (77.27%) who experienced severe ADRs: Tachycardia and/or arrhythmia, carried an abnormal rs806365 gene (CT and CC alleles). Conclusions: The results propose that the rs806365 gene is widely distributed amongst the Thai population and there is a link between this gene and vulnerability to developing THC-induced ADRs after being treated with medical cannabis. Therefore, it is necessary to screen for the rs806365 gene before using medical cannabis to treat a patient.

Keywords: rs806365, THC-induced adverse drug reactions, CB1 receptor, Thai population

Procedia PDF Downloads 101

Authors: Shouta Sora, Shizuki Kuriu, Radhika Mishra, Ariunbuyan Sukhbaatar, Maya Sakamoto, Shiro Mori, Tetsuya Kodama

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Lymph node (LN) metastasis accounts for 20 - 30 % of all deaths in patients with head and neck cancer. Therefore, the control of metastatic lymph nodes (MLNs) is necessary to improve the life prognosis of patients with cancer. In a classical metastatic theory, tumor cells are thought to metastasize hematogenously through a bead-like network of lymph nodes. Recently, a lymph node-mediated hematogenous metastasis theory has been proposed, in which sentinel LNs are regarded as a source of distant metastasis. Therefore, the treatment of MLNs at the early stage is essential to prevent distant metastasis. Radiation therapy is one of the primary therapeutic modalities in cancer treatment. In addition, total body irradiation (TBI) has been reported to act as activation of natural killer cells and increase of infiltration of CD4+ T-cells to tumor tissues. However, the treatment effect of TBI for MLNs remains unclear. This study evaluated the possibilities of low-dose total body irradiation (L-TBI) and middle-dose total body irradiation (M-TBI) for the treatment of MLNs. Mouse breast cancer FM3A-Luc cells were injected into subiliac lymph node (SiLN) of MXH10/Mo/LPR mice to induce the metastasis to the proper axillary lymph node (PALN) and lung. Mice were irradiated for the whole body on 4 days after tumor injection. The L-TBI and M-TBI were defined as irradiations to the whole body at 0.2 Gy and 1.0 Gy, respectively. Tumor growth was evaluated by in vivo bioluminescence imaging system. In the non-irradiated group, tumor activities on SiLN and PALN significantly increased over time, and the metastasis to the lung from LNs was confirmed 28 days after tumor injection. The L-TBI led to a tumor growth delay in PALN but did not control tumor growth in SiLN and metastasis to the lung. In contrast, it was found that the M-TBI significantly delayed the tumor growth of both SiLN and PALN and controlled the distant metastasis to the lung compared with non-irradiated and L-TBI groups. These results suggest that the M-TBI is an effective treatment method for MLNs in the early stage and distant metastasis from lymph nodes via blood vessels connected with LNs.

Keywords: metastatic lymph node, lung metastasis, radiation therapy, total body irradiation, lymphatic system

Procedia PDF Downloads 181

Authors: Ji Jiazheng, Wang Jingrao, Jin Xin, Zhang Hong

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Diabetes mellitus is a metabolic disease characterized by high blood sugar. A long-standing hyperglycemic state can lead to various tissue damage. Diabetic retinopathy is the most common and widely studied ocular complication and has become the leading cause of blindness in my country. At the same time, diabetes has profound clinically relevant effects on the cornea, leading to keratopathy and vision-threatening. The cornea is an avascular tissue and is sensitive to hyperglycemia, Keratopathy caused by diabetes is usually chronic, they are called diabetic keratopathy or diabetic neurotrophic keratopathy, leading to several diabetic corneal complications including delayed epithelial wound healing, recurrent erosions, neuropathy, loss of sensitivity. Corneal stem cell dysfunction in diabetic patients as an important influencing factor of diabetic keratopathy. The consequences of this condition are often underestimated. The limbus is located between the cornea and the sclera tissue. The limbal stroma consists of a series of radial elevations with fibrovascular centers known as palisades of Vogt (POV). Previous studies have shown that palisades of Vogt (POV), as the main site of limbal stem cells, plays an important role in the homeostasis of the corneal epithelium. Therefore, POV plays a vital role in the healing of corneal epithelial surgery and postoperative evaluation. IVCM can observe the condition of the corneal epithelium at the cellular level. It has profound significance and guidance for the evaluation of limbal and limbal stem cells. We have previously observed structural changes in POV in HSK and HZO patients on IVCM. At present, there have been reports involving limbal stem cell dysfunction in diabetic patients, but the specific pathogenesis is still unclear. However, there are no studies on POV morphological changes in patients with DM. Therefore, we performed statistics and compared the correlation between POV morphological changes and corneal epithelial basal cell density, corneal nerves, and length of disease in DM patients and normal humans using IVCM studies. At the same time, fundoscopy was used to observe the correlation between the thickness of RNFL and the thickness of GCC and POV in diabetic patients. And to observe the correlation between SVD, DVD and POV for research.

Keywords: confocal microscopy, fundus, limbal stem cells, diabetes

Procedia PDF Downloads 83

Authors: Vaishali Patil, Neeraj Masand

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In older people, Alzheimer’s disease (AD) is turning out to be a lethal disease. According to the amyloid hypothesis, aggregation of the amyloid β–protein (Aβ), particularly its 42-residue variant (Aβ42), plays direct role in the pathogenesis of AD. Aβ is generated through sequential cleavage of amyloid precursor protein (APP) by β–secretase (BACE) and γ–secretase (GS). Thus in the treatment of AD, γ-secretase modulators (GSMs) are potential disease-modifying as they selectively lower pathogenic Aβ42 levels by shifting the enzyme cleavage sites without inhibiting γ–secretase activity. This possibly avoids known adverse effects observed with complete inhibition of the enzyme complex. Virtual screening, via drug-like ADMET filter, QSAR and molecular docking analyses, has been utilized to identify novel γ–secretase modulators with sulphonamide nucleus. Based on QSAR analyses and docking score, some novel analogs have been synthesized. The results obtained by in silico studies have been validated by performing in vivo analysis. In the first step, behavioral assessment has been carried out using Scopolamine induced amnesia methodology. Later the same series has been evaluated for neuroprotective potential against the oxidative stress induced by Scopolamine. Biochemical estimation was performed to evaluate the changes in biochemical markers of Alzheimer’s disease such as lipid peroxidation (LPO), Glutathione reductase (GSH), and Catalase. The Scopolamine induced amnesia model has shown increased Acetylcholinesterase (AChE) levels and the inhibitory effect of test compounds in the brain AChE levels have been evaluated. In all the studies Donapezil (Dose: 50µg/kg) has been used as reference drug. The reduced AChE activity is shown by compounds 3f, 3c, and 3e. In the later stage, the most potent compounds have been evaluated for Aβ42 inhibitory profile. It can be hypothesized that this series of alkyl-aryl sulphonamides exhibit anti-AD activity by inhibition of Acetylcholinesterase (AChE) enzyme as well as inhibition of plaque formation on prolong dosage along with neuroprotection from oxidative stress.

Keywords: gamma-secretase inhibitors, Alzzheimer's disease, sulphonamides, QSAR

Procedia PDF Downloads 255

Authors: Portia Murphy, Danica Vasic, Anoja W. Gunaratne, Encarnita Sitchon, Teresita Tugonon, Marou Ison, Antoinette Le Busque, Christelle Pagonis, Thomas J. Borody

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Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder that affects an estimated 11% of the population globally with the most predominant symptoms being abdominal pain, bloating and altered bowel movements. All age groups suffer from IBS although the prevalence of IBS decreases for age groups over 50 years. Women are more likely to suffer from IBS than men. IBS can be categorized into 3 groups based on the type of altered bowel movement: diarrhea-predominant IBS (IBS-D), constipation-predominant IBS (IBS-C) and IBS with mixed bowel habit (IBS-M). The contribution of the gut microbiome to the etiology of IBS is becoming increasingly recognized with rising use of anti-microbial agents. Previous studies on vancomycin and rifaximin used as monotherapy or in combination have been conducted mainly on IBS-C and showed marked improvements in the symptoms. According to our knowledge, no studies reported using these two combinations of antibiotics for IBS-D. Here, we report a consecutive cohort of 18 patients treated with both vancomycin and rifaximin for IBS-D. These patients’ records were reviewed retrospectively. In this cohort, patients ages were between 24-74 years (mean 44 years) and 9 were female. Baseline all patients had diarrhea, 4 with mucus and one with blood. Patients reported other symptoms were abdominal pain (n=11) bloating (n=9), flatulence (n=7), fatigue (n=4) and nausea (n=3). Patients treatments were personalized according to their symptom severity and tolerability and were treated with combination of rifaximin (500 - 3000mg/d) and vancomycin (500mg - 1500mg/d) for an ongoing period. Follow-ups were conducted between 2-32 weeks’ time. Of all patients, 89% patients reported improvement of the symptoms, 1 reported no change and 1 patient’s symptoms got worse. The mechanism of action for both vancomycin and rifaximin involves the inhibition of bacterial cell wall and protein synthesis respectively. The role of these medications in improving the symptoms of this cohort suggests that IBS-D may be microbiome infection driven. In this cohort, similar patient presentations to Clostridium difficile, as well as symptom improvement with the use of rifaximin and particularly vancomycin, suggest that the infectious agent may be an unidentified Clostridium. These preliminary results offer an alternative etiology for IBS-D not previously considered and open the avenue for new research.

Keywords: clostridium deficile, diarrhea predominant Irritable Bowel Syndrome, microbiome, vancomycin/rifaximin combination

Procedia PDF Downloads 131

Authors: Sujesh F. Sujan, Steve W. Jones, Arto Kiviniemi

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The use of Building Information Modelling (BIM) in the Architectural-Engineering-Construction (AEC) industry is a form of systemic innovation. Unlike incremental innovation, (such as the technological development of CAD from hand based drawings to 2D electronically printed drawings) any form of systemic innovation in Project-Based Inter-Organisational Networks requires complete collaboration and results in numerous benefits if adopted and utilised properly. Proper use of BIM involves people collaborating with the use of interoperable BIM compliant tools. The AEC industry globally has been known for its adversarial and fragmented nature where firms take advantage of one another to increase their own profitability. Due to the industry’s nature, getting people to collaborate by unifying their goals is critical to successful BIM adoption. However, this form of innovation is often being forced artificially in the old ways of working which do not suit collaboration. This may be one of the reasons for its low global use even though the technology was developed more than 20 years ago. Therefore, there is a need to develop a metric/method to support and allow industry players to gain confidence in their investment into BIM software and workflow methods. This paper departs from defining systemic risk as a risk that affects all the project participants at a given stage of a project and defines categories of systemic risks. The need to generalise is to allow method applicability to any industry where the category will be the same, but the example of the risk will depend on the industry the study is done in. The method proposed seeks to use individual perception of an example of systemic risk as a key parameter. The significance of this study lies in relating the variance of individual perception of systemic risk to how much the team is collaborating. The method bases its notions on the claim that a more unified range of individual perceptions would mean a higher probability that the team is collaborating better. Since contracts and procurement devise how a project team operates, the method could also break the methodological barrier of highly subjective findings that case studies inflict, which has limited the possibility of generalising between global industries. Since human nature applies in all industries, the authors’ intuition is that perception can be a valuable parameter to study collaboration which is essential especially in projects that utilise systemic innovation such as BIM.

Keywords: building information modelling, perception of risk, systemic innovation, team collaboration

Procedia PDF Downloads 185

Authors: Ziwei Song, Junjun Fan, Jeremy Teo, Yang Yu, Yukun Ma, Jie Yan, Shupei Mo, Lisa Tucker-Kellogg, Peter So, Hanry Yu

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Liver is the center of detoxification and exposed to toxic metabolites all the time. It is highly regenerative after injury, with the ability to restore even after 70% partial hepatectomy. Most of the previous studies were using hepatectomy as injury models for liver regeneration study. There is limited understanding of small-scale liver injury, which can be caused by either low dose drug consumption or hepatocyte routine metabolism. Although these small in situ injuries do not cause immediate symptoms, repeated injuries will lead to aberrant wound healing in liver. Therefore, the cellular dynamics during liver regeneration is critical for our understanding of liver regeneration mechanism. We aim to study the liver regeneration of small-scale in situ liver injury in transgenic mice labeling actin (Lifeact-GFP). Previous studies have been using sample sections and biopsies of liver, which lack real-time information. In order to trace every individual hepatocyte during the regeneration process, we have developed and optimized an intravital imaging system that allows in vivo imaging of mouse liver for consecutive 5 days, allowing real-time cellular tracking and quantification of hepatocytes. We used femtosecond-laser ablation to make controlled and repeatable liver injury model, which mimics the real-life small in situ liver injury. This injury model is the first case of its kind for in vivo study on liver. We found that small-scale in situ liver injury is repaired by the coordination of hypertrophy and migration of hepatocytes. Hypertrophy is only transient at initial phase, while migration is the main driving force to complete the regeneration process. From cellular aspect, Akt/mTOR pathway is activated immediately after injury, which leads to transient hepatocyte hypertrophy. From mechano-sensing aspect, the actin cable, formed at apical surface of wound proximal hepatocytes, provides mechanical tension for hepatocyte migration. This study provides important information on both chemical and mechanical signals that promote liver regeneration of small in situ injury. We conclude that hypertrophy and migration play a dominant role at different stages of liver regeneration.

Keywords: hepatocyte, hypertrophy, intravital imaging, liver regeneration, migration

Procedia PDF Downloads 205

Authors: Josée Charette

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The academic and educational success of immigrant students is a current issue in education, especially in western societies such in the province of Quebec, in Canada. For people who immigrate with school-age children, the success of the family’s migratory project is often measured by the benefits drawn by children from the educational institutions of their host society. In order to support the academic achievement of their children, immigrant parents try to develop practices that derive from their representations of school and related challenges inspired by the socio-cultural context of their country of origin. These findings lead us to the following question: How does strategies implemented by immigrant parents to manage the representational distance between school of their country of origin and school of the host society support or not the academic and educational success of their child? In the context of a qualitative exploratory approach, we have made interviews in the French-, English- and Spanish-languages with 32 newly immigrated parents and 10 of their children. Parents were invited to complete a network of free associations about «School in Quebec» as a premise for the interview. The objective of this communication is to present strategies implemented by immigrant parents to manage the distance between their representations of schools in their country of origin and in the host society, and to explore the influence of this management on their child’s academic and educational trajectories. Data analysis led us to develop various types of strategies, such as continuity, adaptation, resources mobilization, compensation and "return to basics" strategies. These strategies seem to be part of a continuum from oppositional-conflict scenario, in which parental strategies act as a risk factor, to conciliator-integrator scenario, in which parental strategies act as a protective factor for immigrant students’ academic and educational success. In conclusion, we believe that our research helps in providing a more efficient support to immigrant parents and contributes to develop a wider portrait of immigrant students’ academic achievement. In addition, we think that by improving the experience of immigrant families in Quebec schools, a greater number of migratory projects will be effective.

Keywords: immigrant students, family’s migratory project, school of origin and school of host society, immigrants parental strategies

Procedia PDF Downloads 444

Authors: Nalan Kaya, Gonca Ozan, Elif Erdem, Neriman Colakoglu, Enver Ozan

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The toxic effects of tobacco smoke exposure have been detected in numerous studies. Ellagic acid (EA), (2,3,7,8-tetrahydroxy [1]-benzopyranol [5,4,3-cde] benzopyran 5,10-dione), a natural phenolic lactone compound, is found in various plant species including pomegranate, grape, strawberries, blackberries and raspberries. Similar to the other effective antioxidants, EA can safely interact with the free radicals and reduces oxidative stress through the phenolic ring and hydroxyl components in its structure. The aim of the present study was to examine the protective effects of ellagic acid against oxidative damage on lung tissues of rats induced by tobacco smoke. Twenty-four male adult (8 weeks old) Spraque-Dawley rats were divided randomly into 4 equal groups: group I (Control), group II (Tobacco smoke), group III (Tobacco smoke + corn oil) and group IV (Tobacco smoke + ellagic acid). The rats in group II, III and IV, were exposed to tobacco smoke 1 hour twice a day for 12 weeks. In addition to tobacco smoke exposure, 12 mg/kg ellagic acid (dissolved in corn oil), was applied to the rats in group IV by oral gavage. Equal amount of corn oil used in solving ellagic acid was applied to the rats by oral gavage in group III. At the end of the experimental period, rats were decapitated. Lung tissues and blood samples were taken. The lung slides were stained by H&E and Masson’s Trichrome methods. Also, galactin-3 stain was applied. Biochemical analyzes were performed. Vascular congestion and inflammatory cell infiltration in pulmonary interstitium, thickness in interalveolar septum, cytoplasmic vacuolation in some macrophages and galactin-3 positive cells were observed in histological examination of tobacco smoke group. In addition to these findings, hemorrhage in pulmonary interstitium and bronchial lumen was detected in tobacco smoke + corn oil group. Reduced vascular congestion and hemorrhage in pulmoner interstitium and rarely thickness in interalveolar septum were shown in tobacco smoke + EA group. Compared to group-I, group-II GSH level was decreased and MDA level was increased significantly. Nevertheless group-IV GSH level was higher and MDA level was lower than group-II. The results indicate that ellagic acid could protect the lung tissue from the tobacco smoke harmful effects.

Keywords: ellagic acid, lung, rat, tobacco smoke

Procedia PDF Downloads 214

Authors: Roberto Coppo, Francesca Orso, Daniela Dettori, Elena Quaglino, Lei Nie, Mehran M. Sadeghi, Daniela Taverna

Abstract:

Malignant melanoma is currently the fifth most common cancer in the white population and it is fatal in its metastatic stage. Several research studies in recent years have provided evidence that cancer initiation and progression are driven by genetic alterations of the tumor and paracrine interactions between tumor and microenvironment. Scattered data show that the Endothelial and Smooth muscle cell-Derived Neuropilin-like molecule (ESDN) controls cell proliferation and movement of stroma and tumor cells. To investigate the role of ESDN in the tumor microenvironment during melanoma progression, murine melanoma cells (B16 or B16-F10) were injected in ESDN knockout mice in order to evaluate how the absence of ESDN in stromal cells could influence melanoma progression. While no effect was found on primary tumor growth, increased cell extravasation and lung metastasis formation was observed in ESDN knockout mice compared to wild type controls. In order to understand how cancer cells cross the endothelial barrier during metastatic dissemination in an ESDN-null microenvironment, structure, and permeability of lung blood vessels were analyzed. Interestingly, ESDN knockout mice showed structurally altered and more permeable vessels compared to wild type animals. Since cell surface molecules mediate the process of tumor cell extravasation, the expression of a panel of extravasation-related ligands and receptors was analyzed. Importantly, modulations of N-cadherin, E-selectin, ICAM-1 and VAP-1 were observed in ESDN knockout endothelial cells, suggesting the presence of a favorable tumor microenvironment which facilitates melanoma cell extravasation and metastasis formation in the absence of ESDN. Furthermore, a potential contribution of immune cells in tumor dissemination was investigated. An increased recruitment of macrophages in the lungs of ESDN knockout mice carrying subcutaneous B16-F10 tumors was found. In conclusion, our data suggest a functional role of ESDN in the tumor microenvironment during melanoma progression and the identification of the mechanisms that regulate tumor cell extravasation could lead to the development of new therapies to reduce metastasis formation.

Keywords: melanoma, tumor microenvironment, extravasation, cell surface molecules

Procedia PDF Downloads 334

Authors: Shujun Xie, Shirong Zhang, Shenglin Ma

Abstract:

Background: Chronic inflammation might lead to many malignancies, and inadequate resolution could play a crucial role in tumor invasion, progression, and metastases. A randomised, double-blind, placebo-controlled trial shows that IL-1β inhibition with canakinumab could reduce incident lung cancer and lung cancer mortality in patients with atherosclerosis. The process and secretion of proinflammatory cytokine IL-1β are controlled by the inflammasome. Here we showed the correlation of the innate immune system and afatinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) in non-small cell lung cancer. Methods: Murine Bone marrow derived macrophages (BMDMs), peritoneal macrophages (PMs) and THP-1 were used to check the effect of afatinib on the activation of NLRP3 inflammasome. The assembly of NLRP3 inflammasome was check by co-immunoprecipitation of NLRP3 and apoptosis-associated speck-like protein containing CARD (ASC), disuccinimidyl suberate (DSS)-cross link of ASC. Lipopolysaccharide (LPS)-induced sepsis and Alum-induced peritonitis were conducted to confirm that afatinib could inhibit the activation of NLRP3 in vivo. Peripheral blood mononuclear cells (PBMCs) from non-small cell lung cancer (NSCLC) patients before or after taking afatinib were used to check that afatinib inhibits inflammation in NSCLC therapy. Results: Our data showed that afatinib could inhibit the secretion of IL-1β in a dose-dependent manner in macrophage. Moreover, afatinib could inhibit the maturation of IL-1β and caspase-1 without affecting the precursors of IL-1β and caspase-1. Next, we found that afatinib could block the assembly of NLRP3 inflammasome and the ASC speck by blocking the interaction of the sensor protein NLRP3 and the adaptor protein ASC. We also found that afatinib was able to alleviate the LPS-induced sepsis in vivo. Conclusion: Our study found that afatinib could inhibit the activation of NLRP3 inflammasome in macrophage, providing new evidence that afatinib could target the innate immune system to control chronic inflammation. These investigations will provide significant experimental evidence in afatinib as therapeutic drug for non-small cell lung cancer or other tumors and NLRP3-related diseases and will explore new targets for afatinib.

Keywords: inflammasome, afatinib, inflammation, tyrosine kinase inhibitor

Procedia PDF Downloads 118