Search results for: cancer specificity
1017 Glycan Analyzer: Software to Annotate Glycan Structures from Exoglycosidase Experiments
Authors: Ian Walsh, Terry Nguyen-Khuong, Christopher H. Taron, Pauline M. Rudd
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Glycoproteins and their covalently bonded glycans play critical roles in the immune system, cell communication, disease and disease prognosis. Ultra performance liquid chromatography (UPLC) coupled with mass spectrometry is conventionally used to qualitatively and quantitatively characterise glycan structures in a given sample. Exoglycosidases are enzymes that catalyze sequential removal of monosaccharides from the non-reducing end of glycans. They naturally have specificity for a particular type of sugar, its stereochemistry (α or β anomer) and its position of attachment to an adjacent sugar on the glycan. Thus, monitoring the peak movements (both in the UPLC and MS1) after application of exoglycosidases provides a unique and effective way to annotate sugars with high detail - i.e. differentiating positional and linkage isomers. Manual annotation of an exoglycosidase experiment is difficult and time consuming. As such, with increasing sample complexity and the number of exoglycosidases, the analysis could result in manually interpreting hundreds of peak movements. Recently, we have implemented pattern recognition software for automated interpretation of UPLC-MS1 exoglycosidase digestions. In this work, we explain the software, indicate how much time it will save and provide example usage showing the annotation of positional and linkage isomers in Immunoglobulin G, apolipoprotein J, and simple glycan standards.Keywords: bioinformatics, automated glycan assignment, liquid chromatography, mass spectrometry
Procedia PDF Downloads 2001016 Metabolic and Adaptive Laboratory Evolutionary Engineering (ALE) of Saccharomyces cerevisiae for Second Generation Biofuel Production
Authors: Farnaz Yusuf, Naseem A. Gaur
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The increase in environmental concerns, rapid depletion of fossil fuel reserves and intense interest in achieving energy security has led to a global research effort towards developing renewable sources of fuels. Second generation biofuels have attracted more attention recently as the use of lignocellulosic biomass can reduce fossil fuel dependence and is environment-friendly. Xylose is the main pentose and second most abundant sugar after glucose in lignocelluloses. Saccharomyces cerevisiae does not readily uptake and use pentose sugars. For an economically feasible biofuel production, both hexose and pentose sugars must be fermented to ethanol. Therefore, it is important to develop S. cerevisiae host platforms with more efficient xylose utilization. This work aims to construct a xylose fermenting yeast strains with engineered oxido-reductative pathway for xylose metabolism. Engineered strain was further improved by adaptive evolutionary engineering approach. The engineered strain is able to grow on xylose as sole carbon source with the maximum ethanol yield of 0.39g/g xylose and productivity of 0.139g/l/h at 96 hours. The further improvement in strain development involves over expression of pentose phosphate pathway and protein engineering of xylose reductase/xylitol dehydrogenase to change their cofactor specificity in order to reduce xylitol accumulation.Keywords: biofuel, lignocellulosic biomass, saccharomyces cerevisiae, xylose
Procedia PDF Downloads 2141015 An Electrocardiography Deep Learning Model to Detect Atrial Fibrillation on Clinical Application
Authors: Jui-Chien Hsieh
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Background:12-lead electrocardiography(ECG) is one of frequently-used tools to detect atrial fibrillation (AF), which might degenerate into life-threaten stroke, in clinical Practice. Based on this study, the AF detection by the clinically-used 12-lead ECG device has only 0.73~0.77 positive predictive value (ppv). Objective: It is on great demand to develop a new algorithm to improve the precision of AF detection using 12-lead ECG. Due to the progress on artificial intelligence (AI), we develop an ECG deep model that has the ability to recognize AF patterns and reduce false-positive errors. Methods: In this study, (1) 570-sample 12-lead ECG reports whose computer interpretation by the ECG device was AF were collected as the training dataset. The ECG reports were interpreted by 2 senior cardiologists, and confirmed that the precision of AF detection by the ECG device is 0.73.; (2) 88 12-lead ECG reports whose computer interpretation generated by the ECG device was AF were used as test dataset. Cardiologist confirmed that 68 cases of 88 reports were AF, and others were not AF. The precision of AF detection by ECG device is about 0.77; (3) A parallel 4-layer 1 dimensional convolutional neural network (CNN) was developed to identify AF based on limb-lead ECGs and chest-lead ECGs. Results: The results indicated that this model has better performance on AF detection than traditional computer interpretation of the ECG device in 88 test samples with 0.94 ppv, 0.98 sensitivity, 0.80 specificity. Conclusions: As compared to the clinical ECG device, this AI ECG model promotes the precision of AF detection from 0.77 to 0.94, and can generate impacts on clinical applications.Keywords: 12-lead ECG, atrial fibrillation, deep learning, convolutional neural network
Procedia PDF Downloads 1141014 Synthesis of Monocyclic, Bicyclic, and Benzocyclobutene Amino Endoperoxides through Visible Light Catalysis
Authors: Enoch Kudoahor, Nan Zheng
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We describe the use of readily available self-doped TiO2 and visible light, under a mild condition to synthesize a class of monocyclic, bicyclic, and benzocyclobutene amino compounds containing the endoperoxide bridges; their derivatives and further test their effective clinical activities against malaria, cancer, and their resistances. Considering their stable under photooxidation conditions and recyclability, we use a self-doped TiO2 under a visible condition to synthesize these classes of amino endoperoxides. These amino endoperoxides are stable over a period compared to classes of endoperoxides.Keywords: catalysis, endoperoxides, titanium dioxide, visible light
Procedia PDF Downloads 1541013 RP-HPLC Method Development and Its Validation for Simultaneous Estimation of Metoprolol Succinate and Olmesartan Medoxomil Combination in Bulk and Tablet Dosage Form
Authors: S. Jain, R. Savalia, V. Saini
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A simple, accurate, precise, sensitive and specific RP-HPLC method was developed and validated for simultaneous estimation of Metoprolol Succinate and Olmesartan Medoxomil in bulk and tablet dosage form. The RP-HPLC method has shown adequate separation for Metoprolol Succinate and Olmesartan Medoxomil from its degradation products. The separation was achieved on a Phenomenex luna ODS C18 (250mm X 4.6mm i.d., 5μm particle size) with an isocratic mixture of acetonitrile: 50mM phosphate buffer pH 4.0 adjusted with glacial acetic acid in the ratio of 55:45 v/v. The mobile phase at a flow rate of 1.0ml/min, Injection volume 20μl and wavelength of detection was kept at 225nm. The retention time for Metoprolol Succinate and Olmesartan Medoxomil was 2.451±0.1min and 6.167±0.1min, respectively. The linearity of the proposed method was investigated in the range of 5-50μg/ml and 2-20μg/ml for Metoprolol Succinate and Olmesartan Medoxomil, respectively. Correlation coefficient was 0.999 and 0.9996 for Metoprolol Succinate and Olmesartan Medoxomil, respectively. The limit of detection was 0.2847μg/ml and 0.1251μg/ml for Metoprolol Succinate and Olmesartan Medoxomil, respectively and the limit of quantification was 0.8630μg/ml and 0.3793μg/ml for Metoprolol and Olmesartan, respectively. Proposed methods were validated as per ICH guidelines for linearity, accuracy, precision, specificity and robustness for estimation of Metoprolol Succinate and Olmesartan Medoxomil in commercially available tablet dosage form and results were found to be satisfactory. Thus the developed and validated stability indicating method can be used successfully for marketed formulations.Keywords: metoprolol succinate, olmesartan medoxomil, RP-HPLC method, validation, ICH
Procedia PDF Downloads 3151012 Full Mini Nutritional Assessment Questionnaire and the Risk of Malnutrition and Mortality in Elderly, Hospitalized Patients: A Cross-Sectional Study
Authors: Christos E. Lampropoulos, Maria Konsta, Tamta Sirbilatze, Ifigenia Apostolou, Vicky Dradaki, Konstantina Panouria, Irini Dri, Christina Kordali, Vaggelis Lambas, Georgios Mavras
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Objectives: Full Mini Nutritional Assessment (MNA) questionnaire is one of the most useful tools in diagnosis of malnutrition in hospitalized patients, which is related to increased morbidity and mortality. The purpose of our study was to assess the nutritional status of elderly, hospitalized patients and examine the hypothesis that MNA may predict mortality and extension of hospitalization. Methods: One hundred fifty patients (78 men, 72 women, mean age 80±8.2) were included in this cross-sectional study. The following data were taken into account in analysis: anthropometric and laboratory data, physical activity (International Physical Activity Questionnaires, IPAQ), smoking status, dietary habits, cause and duration of current admission, medical history (co-morbidities, previous admissions). Primary endpoints were mortality (from admission until 6 months afterwards) and duration of admission. The latter was compared to national guidelines for closed consolidated medical expenses. Logistic regression and linear regression analysis were performed in order to identify independent predictors for mortality and extended hospitalization respectively. Results: According to MNA, nutrition was normal in 54/150 (36%) of patients, 46/150 (30.7%) of them were at risk of malnutrition and the rest 50/150 (33.3%) were malnourished. After performing multivariate logistic regression analysis we found that the odds of death decreased 20% per each unit increase of full MNA score (OR=0.8, 95% CI 0.74-0.89, p < 0.0001). Patients who admitted due to cancer were 23 times more likely to die, compared to those with infection (OR=23, 95% CI 3.8-141.6, p=0.001). Similarly, patients who admitted due to stroke were 7 times more likely to die (OR=7, 95% CI 1.4-34.5, p=0.02), while these with all other causes of admission were less likely (OR=0.2, 95% CI 0.06-0.8, p=0.03), compared to patients with infection. According to multivariate linear regression analysis, each increase of unit of full MNA, decreased the admission duration on average 0.3 days (b:-0.3, 95% CI -0.45 - -0.15, p < 0.0001). Patients admitted due to cancer had on average 6.8 days higher extension of hospitalization, compared to those admitted for infection (b:6.8, 95% CI 3.2-10.3, p < 0.0001). Conclusion: Mortality and extension of hospitalization is significantly increased in elderly, malnourished patients. Full MNA score is a useful diagnostic tool of malnutrition.Keywords: duration of admission, malnutrition, mini nutritional assessment score, prognostic factors for mortality
Procedia PDF Downloads 3131011 Magnesium Nanoparticles for Photothermal Therapy
Authors: E. Locatelli, I. Monaco, R. C. Martin, Y. Li, R. Pini, M. Chiariello, M. Comes Franchini
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Despite the many advantages of application of nanomaterials in the field of nanomedicine, increasing concerns have been expressed on their potential adverse effects on human health. There is urgency for novel green strategies toward novel materials with enhanced biocompatibility using safe reagents. Photothermal ablation therapy, which exploits localized heat increase of a few degrees to kill cancer cells, has appeared recently as a non-invasive and highly efficient therapy against various cancer types; anyway new agents able to generate hyperthermia when irradiated are needed and must have precise biocompatibility in order to avoid damage to healthy tissues and prevent toxicity. Recently, there has been increasing interest in magnesium as a biomaterial: it is the fourth most abundant cation in the human body, and it is essential for human metabolism. However magnesium nanoparticles (Mg NPs) have had limited diffusion due to the high reduction potential of magnesium cations, which makes NPs synthesis challenging. Herein, we report the synthesis of Mg NPs and their surface functionalization for the obtainment of a stable and biocompatible nanomaterial suitable for photothermal ablation therapy against cancer. We synthesized the Mg crystals by reducing MgCl2 with metallic lithium and exploiting naphthalene as an electron carrier: the lithium–naphthalene complex acts as the real reducing agent. Firstly, the nanocrystal particles were coated with the ligand 12-ethoxy ester dodecanehydroxamic acid, and then entrapped into water-dispersible polymeric micelles (PMs) made of the FDA-approved PLGA-b-PEG-COOH copolymer using the oil-in-water emulsion technique. Lately, we developed a more straightforward methodology by introducing chitosan, a highly biocompatible natural product, at the beginning of the process, simultaneously using lithium–naphthalene complex, thus having a one-pot procedure for the formation and surface modification of MgNPs. The obtained MgNPs were purified and fully characterized, showing diameters in the range of 50-300 nm. Notably, when coated with chitosan the particles remained stable as dry powder for more than 10 months. We proved the possibility of generating a temperature rise of a few to several degrees once MgNPs were illuminated using a 810 nm diode laser operating in continuous wave mode: the temperature rise resulted significant (0-15 °C) and concentration dependent. We then investigated potential cytotoxicity of the MgNPs: we used HN13 epithelial cells, derived from a head and neck squamous cell carcinoma and the hepa1-6 cell line, derived from hepatocellular carcinoma and very low toxicity was observed for both nanosystems. Finally, in vivo photothermal therapy was performed on xenograft hepa1-6 tumor bearing mice: the animals were treated with MgNPs coated with chitosan and showed no sign of suffering after the injection. After 12 hours the tumor was exposed to near-infrared laser light. The results clearly showed an extensive damage to tumor tissue after only 2 minutes of laser irradiation at 3Wcm-1, while no damage was reported when the tumor was treated with the laser and saline alone in control group. Despite the lower photothermal efficiency of Mg with respect to Au NPs, we consider MgNPs a promising, safe and green candidate for future clinical translations.Keywords: chitosan, magnesium nanoparticles, nanomedicine, photothermal therapy
Procedia PDF Downloads 2701010 Oncolytic Efficacy of Thymidine Kinase-Deleted Vaccinia Virus Strain Tiantan (oncoVV-TT) in Glioma
Authors: Seyedeh Nasim Mirbahari, Taha Azad, Mehdi Totonchi
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Oncolytic viruses, which only replicate in tumor cells, are being extensively studied for their use in cancer therapy. A particular virus known as the vaccinia virus, a member of the poxvirus family, has demonstrated oncolytic abilities glioma. Treating Glioma with traditional methods such as chemotherapy and radiotherapy is quite challenging. Even though oncolytic viruses have shown immense potential in cancer treatment, their effectiveness in glioblastoma treatment is still low. Therefore, there is a need to improve and optimize immunotherapies for better results. In this study, we have designed oncoVV-TT, which can more effectively target tumor cells while minimizing replication in normal cells by replacing the thymidine kinase gene with a luc-p2a-GFP gene expression cassette. Human glioblastoma cell line U251 MG, rat glioblastoma cell line C6, and non-tumor cell line HFF were plated at 105 cells in a 12-well plates in 2 mL of DMEM-F2 medium with 10% FBS added to each well. Then incubated at 37°C. After 16 hours, the cells were treated with oncoVV-TT at an MOI of 0.01, 0.1 and left in the incubator for a further 24, 48, 72 and 96 hours. Viral replication assay, fluorescence imaging and viability tests, including trypan blue and crystal violet, were conducted to evaluate the cytotoxic effect of oncoVV-TT. The finding shows that oncoVV-TT had significantly higher cytotoxic activity and proliferation rates in tumor cells in a dose and time-dependent manner, with the strongest effect observed in U251 MG. To conclude, oncoVV-TT has the potential to be a promising oncolytic virus for cancer treatment, with a more cytotoxic effect in human glioblastoma cells versus rat glioma cells. To assess the effectiveness of vaccinia virus-mediated viral therapy, we have tested U251mg and C6 tumor cell lines taken from human and rat gliomas, respectively. The study evaluated oncoVV-TT's ability to replicate and lyse cells and analyzed the survival rates of the tested cell lines when treated with different doses of oncoVV-TT. Additionally, we compared the sensitivity of human and mouse glioma cell lines to the oncolytic vaccinia virus. All experiments regarding viruses were conducted under biosafety level 2. We engineered a Vaccinia-based oncolytic virus called oncoVV-TT to replicate specifically in tumor cells. To propagate the oncoVV-TT virus, HeLa cells (5 × 104/well) were plated in 24-well plates and incubated overnight to attach to the bottom of the wells. Subsequently, 10 MOI virus was added. After 48 h, cells were harvested by scraping, and viruses were collected by 3 sequential freezing and thawing cycles followed by removal of cell debris by centrifugation (1500 rpm, 5 min). The supernatant was stored at −80 ◦C for the following experiments. To measure the replication of the virus in Hela, cells (5 × 104/well) were plated in 24-well plates and incubated overnight to attach to the bottom of the wells. Subsequently, 5 MOI virus or equal dilution of PBS was added. At the treatment time of 0 h, 24 h, 48 h, 72 h and 96 h, the viral titers were determined under the fluorescence microscope (BZ-X700; Keyence, Osaka, Japan). Fluorescence intensity was quantified using the imagej software according to the manufacturer’s protocol. For the isolation of single-virus clones, HeLa cells seeded in six-well plates (5×105 cells/well). After 24 h (100% confluent), the cells were infected with a 10-fold dilution series of TianTan green fluorescent protein (GFP)virus and incubated for 4 h. To examine the cytotoxic effect of oncoVV-TT virus ofn U251mg and C6 cell, trypan blue and crystal violet assay was used.Keywords: oncolytic virus, immune therapy, glioma, vaccinia virus
Procedia PDF Downloads 791009 Nursing System Development in Patients Undergoing Operation in 3C Ward
Authors: Darawan Augsornwan, Artitaya Sabangbal, Maneewan Srijan, Kanokarn Kongpitee, Lalida Petphai, Palakorn Surakunprapha
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Background: Srinagarind Hospital, Ward 3C, has patients with head and neck cancer, congenital urology anomalies such as hypospadis, cleft lip and cleft palate and congenital megacolon who need surgery. Undergoing surgery is a difficult time for patients/ family; they feel fear and anxiety. Nurses work closely with patients and family for 24 hours in the process of patients care, so should have the good nursing ability, innovation and an efficient nursing care system to promote patients self-care ability reducing suffering and preventing complications. From previous nursing outcomes we found patients did not receive appropriate information, could not take care of their wound, not early ambulation after the operation and lost follow-up. Objective: to develop the nursing system for patients who were undergoing an operation. Method: this is a participation action research. The sample population was 11 nurses and 60 patients. This study was divided into 3 phase: Phase 1. Situation review In this phase we review the clinical outcomes, the process of care from documents such as nurses note and interview nurses, patients and family about the process of care by nurses. Phase 2: focus group with 11 nurses, searching guideline for specific care, nursing care system then establish the protocol. This phase we have the protocol for giving information, teaching protocol and teaching record, leaflet for all of top five diseases, make video media to convey information, ambulation package and protocol for patients with head and neck cancer, patients zoning, primary nurse, improved job description for each staff level. Program to record number of patients, kind of medical procedures for showing nurses activity each day. Phase 3 implementation and evaluation. Result: patients/family receive appropriate information about deep breathing exercise, cough, early ambulation after the operation, information during the stay in the hospital. Patients family satisfaction is 95.04 percent, appropriate job description for a practical nurse, nurse aid, and worker. Nurses satisfaction is 95 percent. The complications can be prevented. Conclusion: the nursing system is the dynamic process using evidence to develop nursing care. The appropriate system depends on context and needs to keep an eye on every event.Keywords: development, nursing system, patients undergoing operation, 3C Ward
Procedia PDF Downloads 2651008 Patient Outcomes Following Out-of-Hospital Cardiac Arrest
Authors: Scott Ashby, Emily Granger, Mark Connellan
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Background: In-hospital management of Out-of-Hospital Cardiac Arrest (OHCA) is complex as the aetiologies are varied. Acute coronary angiography has been shown to improve outcomes for patients with coronary occlusion as the cause; however, these patients are difficult to identify. ECG results may help identify these patients, but the accuracy of this diagnostic test is under debate, and requires further investigation. Methods: Arrest and hospital management information was collated retrospectively for OHCA patients who presented to a single clinical site between 2009 and 2013. Angiography results were then collected and checked for significance with survival to discharge. The presence of a severe lesion (>70%) was then compared to categorised ECG findings, and the accuracy of the test was calculated. Results: 104 patients were included in this study, 44 survived to discharge, 52 died and 8 were transferred to other clinical sites. Angiography appears to significantly correlate with survival to discharge. ECG showed 54.8% sensitivity for detecting the presence of a severe lesion within the group that received angiography. A combined criterion including any ECG pathology showed 100% sensitivity and negative predictive value, however, a low specificity and positive predictive value. Conclusion: In the cohort investigated, ST elevation on ECG is not a sensitive enough screening test to be used to determine whether OHCA patients have coronary stenosis as the likely cause of their arrest, and more investigation into whether screening with a combined ECG criterion, or whether all patients should receive angiography routinely following OHCA is needed.Keywords: out of hospital cardiac arrest, coronary angiography, resuscitation, emergency medicine
Procedia PDF Downloads 3951007 Soy Candle vs Paraffin Candle
Authors: Otana A. Jakpor
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Air pollution is without a doubt one of the gravest environmental threats the world is facing today in terms of its sheer toll on human lives. Each year an estimated 70,000 Americans lose their lives to air pollution -- a number equal to deaths from both breast and prostate cancer combined. Since Americans spend nearly 90% of their time indoors, more research is needed on indoor air pollution and common exposures such as candles. Paraffin wax is a by-product of petroleum, and similarities have been observed between fine particulate emissions from paraffin candles and diesel exhaust. The purpose of this study is to determine whether or not paraffin candles are a major potential source of indoor air pollution. Furthermore, this study aims to determine whether or not soy candles are a safer, cleaner alternative to paraffin candles.Keywords: soy candle, soy, paraffin candle, paraffin
Procedia PDF Downloads 2551006 Introduce a New Model of Anomaly Detection in Computer Networks Using Artificial Immune Systems
Authors: Mehrshad Khosraviani, Faramarz Abbaspour Leyl Abadi
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The fundamental component of the computer network of modern information society will be considered. These networks are connected to the network of the internet generally. Due to the fact that the primary purpose of the Internet is not designed for, in recent decades, none of these networks in many of the attacks has been very important. Today, for the provision of security, different security tools and systems, including intrusion detection systems are used in the network. A common diagnosis system based on artificial immunity, the designer, the Adhasaz Foundation has been evaluated. The idea of using artificial safety methods in the diagnosis of abnormalities in computer networks it has been stimulated in the direction of their specificity, there are safety systems are similar to the common needs of m, that is non-diagnostic. For example, such methods can be used to detect any abnormalities, a variety of attacks, being memory, learning ability, and Khodtnzimi method of artificial immune algorithm pointed out. Diagnosis of the common system of education offered in this paper using only the normal samples is required for network and any additional data about the type of attacks is not. In the proposed system of positive selection and negative selection processes, selection of samples to create a distinction between the colony of normal attack is used. Copa real data collection on the evaluation of ij indicates the proposed system in the false alarm rate is often low compared to other ir methods and the detection rate is in the variations.Keywords: artificial immune system, abnormality detection, intrusion detection, computer networks
Procedia PDF Downloads 3531005 Nanorods Based Dielectrophoresis for Protein Concentration and Immunoassay
Authors: Zhen Cao, Yu Zhu, Junxue Fu
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Immunoassay, i.e., antigen-antibody reaction, is crucial for disease diagnostics. To achieve the adequate signal of the antigen protein detection, a large amount of sample and long incubation time is needed. However, the amount of protein is usually small at the early stage, which makes it difficult to detect. Unlike cells and DNAs, no valid chemical method exists for protein amplification. Thus, an alternative way to improve the signal is through particle manipulation techniques to concentrate proteins, among which dielectrophoresis (DEP) is an effective one. DEP is a technique that concentrates particles to the designated region through a force created by the gradient in a non-uniform electric field. Since DEP force is proportional to the cube of particle size and square of electric field gradient, it is relatively easy to capture larger particles such as cells. For smaller ones like proteins, a super high gradient is then required. In this work, three-dimensional Ag/SiO2 nanorods arrays, fabricated by an easy physical vapor deposition technique called as oblique angle deposition, have been integrated with a DEP device and created the field gradient as high as of 2.6×10²⁴ V²/m³. The nanorods based DEP device is able to enrich bovine serum albumin (BSA) protein by 1800-fold and the rate has reached 180-fold/s when only applying 5 V electric potential. Based on the above nanorods integrated DEP platform, an immunoassay of mouse immunoglobulin G (IgG) proteins has been performed. Briefly, specific antibodies are immobilized onto nanorods, then IgG proteins are concentrated and captured, and finally, the signal from fluorescence-labelled antibodies are detected. The limit of detection (LoD) is measured as 275.3 fg/mL (~1.8 fM), which is a 20,000-fold enhancement compared with identical assays performed on blank glass plates. Further, prostate-specific antigen (PSA), which is a cancer biomarker for diagnosis of prostate cancer after radical prostatectomy, is also quantified with a LoD as low as 2.6 pg/mL. The time to signal saturation has been significantly reduced to one minute. In summary, together with an easy nanorod fabrication and integration method, this nanorods based DEP platform has demonstrated highly sensitive immunoassay performance and thus poses great potentials in applications for early point-of-care diagnostics.Keywords: dielectrophoresis, immunoassay, oblique angle deposition, protein concentration
Procedia PDF Downloads 1031004 A Pipeline for Detecting Copy Number Variation from Whole Exome Sequencing Using Comprehensive Tools
Authors: Cheng-Yang Lee, Petrus Tang, Tzu-Hao Chang
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Copy number variations (CNVs) have played an important role in many kinds of human diseases, such as Autism, Schizophrenia and a number of cancers. Many diseases are found in genome coding regions and whole exome sequencing (WES) is a cost-effective and powerful technology in detecting variants that are enriched in exons and have potential applications in clinical setting. Although several algorithms have been developed to detect CNVs using WES and compared with other algorithms for finding the most suitable methods using their own samples, there were not consistent datasets across most of algorithms to evaluate the ability of CNV detection. On the other hand, most of algorithms is using command line interface that may greatly limit the analysis capability of many laboratories. We create a series of simulated WES datasets from UCSC hg19 chromosome 22, and then evaluate the CNV detective ability of 19 algorithms from OMICtools database using our simulated WES datasets. We compute the sensitivity, specificity and accuracy in each algorithm for validation of the exome-derived CNVs. After comparison of 19 algorithms from OMICtools database, we construct a platform to install all of the algorithms in a virtual machine like VirtualBox which can be established conveniently in local computers, and then create a simple script that can be easily to use for detecting CNVs using algorithms selected by users. We also build a table to elaborate on many kinds of events, such as input requirement, CNV detective ability, for all of the algorithms that can provide users a specification to choose optimum algorithms.Keywords: whole exome sequencing, copy number variations, omictools, pipeline
Procedia PDF Downloads 3191003 A Comparative Analysis on Survival in Patients with Node Positive Cutaneous Head and Neck Squamous Cell Carcinoma as per TNM 7th and Tnm 8th Editions
Authors: Petr Daniel Edward Kovarik, Malcolm Jackson, Charles Kelly, Rahul Patil, Shahid Iqbal
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Introduction: Recognition of the presence of extra capsular spread (ECS) has been a major change in the TNM 8th edition published by the American Joint Committee on Cancer in 2018. Irrespective of the size or number of lymph nodes, the presence of ECS makes N3b disease a stage IV disease. The objective of this retrospective observational study was to conduct a comparative analysis of survival outcomes in patients with lymph node-positive cutaneous head and neck squamous cell carcinoma (CHNSCC) based on their TNM 7th and TNM 8th editions classification. Materials and Methods: From January 2010 to December 2020, 71 patients with CHNSCC were identified from our centre’s database who were treated with radical surgery and adjuvant radiotherapy. All histopathological reports were reviewed, and comprehensive nodal mapping was performed. The data were collected retrospectively and survival outcomes were compared using TNM 7th and 8th editions. Results: The median age of the whole group of 71 patients was 78 years, range 54 – 94 years, 63 were male and 8 female. In total, 2246 lymph nodes were analysed; 195 were positive for cancer. ECS was present in 130 lymph nodes, which led to a change in TNM staging. The details on N-stage as per TNM 7th edition was as follows; pN1 = 23, pN2a = 14, pN2b = 32, pN2c = 0, pN3 = 2. After incorporating the TNM 8th edition criterion (presence of ECS), the details on N-stage were as follows; pN1 = 6, pN2a = 5, pN2b = 3, pN2c = 0, pN3a = 0, pN3b = 57. This showed an increase in overall stage. According to TNM 7th edition, there were 23 patients were with stage III and remaining 48 patients, stage IV. As per TNM 8th edition, there were only 6 patients with stage III as compared to 65 patients with stage IV. For all patients, 2-year disease specific survival (DSS) and overall survival (OS) were 70% and 46%. 5-year DSS and OS rates were 66% and 20% respectively. Comparing the survival between stage III and stage IV of the two cohorts using both TNM 7th and 8th editions, there is an obvious greater survival difference between the stages if TNM 8th staging is used. However, meaningful statistics were not possible as the majority of patients (n = 65) were with stage IV and only 6 patients were stage III in the TNM 8th cohort. Conclusion: Our study provides a comprehensive analysis on lymph node data mapping in this specific patient population. It shows a better differentiation between stage III and stage IV in the TNM 8th edition as compared to TNM 7th however meaningful statistics were not possible due to the imbalance of patients in the sub-cohorts of the groups.Keywords: cutaneous head and neck squamous cell carcinoma, extra capsular spread, neck lymphadenopathy, TNM 7th and 8th editions
Procedia PDF Downloads 1071002 Systems Strengthening for Sustainable Family Planning Service Provision in Uganda
Authors: D. Muyama, M. Luyiga, P. Buyungo, D. Chemonges, M. Namukwaya, L. Ssekabembe, B. Lukwago, D. Kyamagwa
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Context: The study focuses on the sustainability of health interventions in Uganda, particularly in the private sector, beyond donor-funded project periods. The Population Services International (PSI) implemented the Women Health Project (WHP) to ensure continued access to quality family planning, cervical cancer screening, and post-abortion care services through private clinics. Research Aim: The aim of the study is to assess the continued access to quality family planning, cervical cancer screening, and post-abortion care services through the private sector after the closure or reduction in funding of the WHP. Methodology: PSI trained and mentored 83 clinics to establish functional systems in self-regulatory quality improvement, supply chain, referral, and demand creation. The clinics were also connected to the national reporting system and utilized Ministry of Health reporting tools. An assessment tool with six criteria was designed and used to evaluate the progress of the clinics. Clinics scoring 75% and above were considered independent and graduated from the program. Findings: Out of the 83 private clinics, 56 successfully met the graduation criteria and graduated from the program, while 25 lost interest and were gradually dropped. Two clinics failed to achieve the criteria due to leadership challenges. The 59 graduating clinics continued to provide high-quality family planning services, including IUD, implant, Depo-Provera, oral contraceptives, and post-abortion care. All graduating clinics were reassessed and found to still be capable of offering services, attributing their success to government stock availability and acquired skills through mentorships. The clinics expressed appreciation to PSI for the sustainable plan that allowed them to operate beyond the project period. Theoretical Importance: This study contributes to the understanding of sustainability planning and the importance of clinic owners' attitudes and buy-in for continued service provision. It emphasizes the implementation of sustainability plans through existing structures to leverage available resources and ensure continuity of care. Data Collection and Analysis Procedures: The study collected data through the assessment tool that evaluated the progress of clinics based on the established criteria. The tool was scored out of 100%, and clinics scoring above 75% were deemed independent. The findings were analyzed quantitatively to determine the success rate of clinics in meeting the graduation criteria. Questions Addressed: The study addresses the question of whether private clinics in Uganda can sustain the provision of family planning, cervical cancer screening, and post-abortion care services after the closure or reduction in funding of the WHP. Conclusion: The study concludes that the attitude and buy-in of clinic owners are essential for sustainability planning. Implementing sustainability plans through existing structures and leveraging available resources are crucial for the continuity of care after the end of a project or reduced funding. The findings highlight the importance of establishing sustainable plans to ensure continued access to essential health services beyond the project period. Contributions: This study contributes to the existing knowledge for programmers implementing or intending to implement donor-funded projects. It provides insights into designing sustainable plans that enable the independent operation of clinics even after the end of a project.Keywords: graduation, family planning, systems strengthening, sustainability
Procedia PDF Downloads 661001 Prospective Validation of the FibroTest Score in Assessing Liver Fibrosis in Hepatitis C Infection with Genotype 4
Authors: G. Shiha, S. Seif, W. Samir, K. Zalata
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Prospective Validation of the FibroTest Score in assessing Liver Fibrosis in Hepatitis C Infection with Genotype 4 FibroTest (FT) is non-invasive score of liver fibrosis that combines the quantitative results of 5 serum biochemical markers (alpha-2-macroglobulin, haptoglobin, apolipoprotein A1, gamma glutamyl transpeptidase (GGT) and bilirubin) and adjusted with the patient's age and sex in a patented algorithm to generate a measure of fibrosis. FT has been validated in patients with chronic hepatitis C (CHC) (Halfon et al., Gastroenterol. Clin Biol.( 2008), 32 6suppl 1, 22-39). The validation of fibro test ( FT) in genotype IV is not well studied. Our aim was to evaluate the performance of FibroTest in an independent prospective cohort of hepatitis C patients with genotype 4. Subject was 122 patients with CHC. All liver biopsies were scored using METAVIR system. Our fibrosis score(FT) were measured, and the performance of the cut-off score were done using ROC curve. Among patients with advanced fibrosis, the FT was identically matched with the liver biopsy in 18.6%, overestimated the stage of fibrosis in 44.2% and underestimated the stage of fibrosis in 37.7% of cases. Also in patients with no/mild fibrosis, identical matching was detected in 39.2% of cases with overestimation in 48.1% and underestimation in 12.7%. So, the overall results of the test were identical matching, overestimation and underestimation in 32%, 46.7% and 21.3% respectively. Using ROC curve it was found that (FT) at the cut-off point of 0.555 could discriminate early from advanced stages of fibrosis with an area under ROC curve (AUC) of 0.72, sensitivity of 65%, specificity of 69%, PPV of 68%, NPV of 66% and accuracy of 67%. As FibroTest Score overestimates the stage of advanced fibrosis, it should not be considered as a reliable surrogate for liver biopsy in hepatitis C infection with genotype 4.Keywords: fibrotest, chronic Hepatitis C, genotype 4, liver biopsy
Procedia PDF Downloads 4151000 Prevalence of Cyp2d6 and Its Implications for Personalized Medicine in Saudi Arabs
Authors: Hamsa T. Tayeb, Mohammad A. Arafah, Dana M. Bakheet, Duaa M. Khalaf, Agnieszka Tarnoska, Nduna Dzimiri
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Background: CYP2D6 is a member of the cytochrome P450 mixed-function oxidase system. The enzyme is responsible for the metabolism and elimination of approximately 25% of clinically used drugs, especially in breast cancer and psychiatric therapy. Different phenotypes have been described displaying alleles that lead to a complete loss of enzyme activity, reduced function (poor metabolizers – PM), hyperfunctionality (ultrarapid metabolizers–UM) and therefore drug intoxication or loss of drug effect. The prevalence of these variants may vary among different ethnic groups. Furthermore, the xTAG system has been developed to categorized all patients into different groups based on their CYP2D6 substrate metabolization. Aim of the study: To determine the prevalence of the different CYP2D6 variants in our population, and to evaluate their clinical relevance in personalized medicine. Methodology: We used the Luminex xMAP genotyping system to sequence 305 Saudi individuals visiting the Blood Bank of our Institution and determine which polymorphisms of CYP2D6 gene are prevalent in our region. Results: xTAG genotyping showed that 36.72% (112 out of 305 individuals) carried the CYP2D6_*2. Out of the 112 individuals with the *2 SNP, 6.23% had multiple copies of *2 SNP (19 individuals out of 305 individuals), resulting in an UM phenotype. About 33.44% carried the CYP2D6_*41, which leads to decreased activity of the CYP2D6 enzyme. 19.67% had the wild-type alleles and thus had normal enzyme function. Furthermore, 15.74% carried the CYP2D6_*4, which is the most common nonfunctional form of the CYP2D6 enzyme worldwide. 6.56% carried the CYP2D6_*17, resulting in decreased enzyme activity. Approximately 5.73% carried the CYP2D6_*10, consequently decreasing the enzyme activity, resulting in a PM phenotype. 2.30% carried the CYP2D6_*29, leading to decreased metabolic activity of the enzyme, and 2.30% carried the CYP2D6_*35, resulting in an UM phenotype, 1.64% had a whole-gene deletion CYP2D6_*5, thus resulting in the loss of CYP2D6 enzyme production, 0.66% carried the CYP2D6_*6 variant. One individual carried the CYP2D6_*3(B), producing an inactive form of the enzyme, which leads to decrease of enzyme activity, resulting in a PM phenotype. Finally, one individual carried the CYP2D6_*9, which decreases the enzyme activity. Conclusions: Our study demonstrates that different CYP2D6 variants are highly prevalent in ethnic Saudi Arabs. This finding sets a basis for informed genotyping for these variants in personalized medicine. The study also suggests that xTAG is an appropriate procedure for genotyping the CYP2D6 variants in personalized medicine.Keywords: CYP2D6, hormonal breast cancer, pharmacogenetics, polymorphism, psychiatric treatment, Saudi population
Procedia PDF Downloads 572999 Correlation Analysis between the Corporate Governance and Financial Performance of Banking Sectors Using Parameter Estimation
Authors: Vishwa Nath Maurya, Rama Shanker Sharma, Saad Talib Hasson Aljebori, Avadhesh Kumar Maurya, Diwinder Kaur Arora
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Present paper deals with problems of determining the relationship between the variables of corporate governance and financial performance of Islamic banks. Here, we dealt with the corporate governance in the banking sector, where increasing the importance of corporate governance, due to their special nature, as the bankruptcy of banks affects not only the relevant parties from customers, depositors and lenders, but also affect financial stability and then the economy as a whole. Through this paper we dealt to the specificity of governance in Islamic banks, which face double governance: Anglo-Saxon governance system and Islamic governance system. In addition, we focused our attention to measure the impact of corporate governance variables on financial performance through an empirical study on a sample of Islamic banks during the period 2005-2012 in the GCC region. Our present study implies that there is a very strong relationship between the variables of governance and financial performance of Islamic banks, where there is a positive relationship between return on assets and the composition of the Board of Directors, the size of the Board of Directors, the number of committees in the Council, as well as the number of members of the Sharia Supervisory Board, while it is clear that there is a negative relationship between return on assets and concentration ownership.Keywords: correlation analysis, parametric estimation, corporate governance, financial performance, financial stability, conventional banks, bankruptcy, Islamic governance system
Procedia PDF Downloads 516998 An Application of Remote Sensing for Modeling Local Warming Trend
Authors: Khan R. Rahaman, Quazi K. Hassan
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Global changes in climate, environment, economies, populations, governments, institutions, and cultures converge in localities. Changes at a local scale, in turn, contribute to global changes as well as being affected by them. Our hypothesis is built on a consideration that temperature does vary at local level (i.e., termed as local warming) in comparison to the predicted models at the regional and/or global scale. To date, the bulk of the research relating local places to global climate change has been top-down, from the global toward the local, concentrating on methods of impact analysis that use as a starting point climate change scenarios derived from global models, even though these have little regional or local specificity. Thus, our focus is to understand such trends over the southern Alberta, which will enable decision makers, scientists, researcher community, and local people to adapt their policies based on local level temperature variations and to act accordingly. Specific objectives in this study are: (i) to understand the local warming (temperature in particular) trend in context of temperature normal during the period 1961-2010 at point locations using meteorological data; (ii) to validate the data by using specific yearly data, and (iii) to delineate the spatial extent of the local warming trends and understanding influential factors to adopt situation by local governments. Existing data has brought the evidence of such changes and future research emphasis will be given to validate this hypothesis based on remotely sensed data (i.e. MODIS product by NASA).Keywords: local warming, climate change, urban area, Alberta, Canada
Procedia PDF Downloads 339997 Microwave-Assisted Synthesis of a Class of Pyridine and Purine Thioglycoside Analogs
Authors: Mamdouh Abu-Zaied, K. Mohamed, Galal A. Nawwar
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Microwave-assisted synthesis of a new class of pyridine or purine thioglycoside analogs from readily available starting materials has been described. The key step of this protocol is the formation of sodium pyridine 4-thiolate 4 and pyrazolo[1,5-a]pyrimidine-7-thiolate 5 derivatives via condensation of 1 with cyanoacetanilide derivative 2 or 5-aminopyrazole derivative 3 respectively under microwave irradiation, followed by coupling with halo sugars to give the corresponding pyridine and purine thioglycoside analogs. The obtained compounds were evaluated in vitro against lung (A549), colon (HCT116), liver (HEPG2), and MCF-7(breast) cancer cell lines. Some of them recorded promising activities.Keywords: antitumor, cyclic sugars, pyrazoles, pyridines, pyrimidines, purines, thioglycosides
Procedia PDF Downloads 241996 Generation of Numerical Data for the Facilitation of the Personalized Hyperthermic Treatment of Cancer with An Interstital Antenna Array Using the Method of Symmetrical Components
Authors: Prodromos E. Atlamazoglou
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The method of moments combined with the method of symmetrical components is used for the analysis of interstitial hyperthermia applicators. The basis and testing functions are both piecewise sinusoids, qualifying our technique as a Galerkin one. The dielectric coatings are modeled by equivalent volume polarization currents, which are simply related to the conduction current distribution, avoiding in that way the introduction of additional unknowns or numerical integrations. The results of our method for a four dipole circular array, are in agreement with those already published in literature for a same hyperthermia configuration. Apart from being accurate, our approach is more general, more computationally efficient and takes into account the coupling between the antennas.Keywords: hyperthermia, integral equations, insulated antennas, method of symmetrical components
Procedia PDF Downloads 257995 Senior Entrepreneurship and the Takeover of Family Businesses: The Case of Moroccan Family-Owned Small Medium-Sized Enterprises
Authors: Brahim Ouzaka, Said Ouhadi
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Family businesses (FB) represent the oldest and most resilient form of organization. However, they are weakened by problems of entrepreneurial discontinuity. The objective of this paper is to analyze the problem of the succession of FBs created by senior entrepreneurs. This study analyzes and explores the constructs of senior entrepreneurship and the strategy and takeover policies of the Moroccan Family owned Small and Medium-Sized Businesses. Our main research question is formulated as follows: how does senior entrepreneurship promote the takeover of Moroccan family SMEs? So we aim through this study to analyze the challenge of the takeover of the FB created by senior entrepreneurs in order to explore and understand the specificities, choices and strategies as well as the reality of the takeover process among this category of senior entrepreneurs. After a review of the literature on the relationship between the constructs of senior entrepreneurship and the takeover of FBs, the empirical study will consist of an exploratory qualitative approach of 3 family SMEs created by senior entrepreneurs and subsequently transmitted to their descendants. This qualitative research serves to explore the choices, the strategies as well as the specificities of the entrepreneurial acts and processes of this category of entrepreneurs. The interviews were conducted with senior entrepreneurs and successors of three Moroccan family SMEs, focusing on the specificity of entrepreneurial actions and strategies in the case of SMEs launched by senior entrepreneurs and on the reality of the conduct and preparation of the takeover process, the methods of socialization and training of buyers in the context of these companies.Keywords: senior entrepreneurship, family SME, family business, takeover
Procedia PDF Downloads 87994 Hybrid Materials on the Basis of Magnetite and Magnetite-Gold Nanoparticles for Biomedical Application
Authors: Mariia V. Efremova, Iana O. Tcareva, Anastasia D. Blokhina, Ivan S. Grebennikov, Anastasia S. Garanina, Maxim A. Abakumov, Yury I. Golovin, Alexander G. Savchenko, Alexander G. Majouga, Natalya L. Klyachko
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During last decades magnetite nanoparticles (NPs) attract a deep interest of scientists due to their potential application in therapy and diagnostics. However, magnetite nanoparticles are toxic and non-stable in physiological conditions. To solve these problems, we decided to create two types of hybrid systems based on magnetite and gold which is inert and biocompatible: gold as a shell material (first type) and gold as separate NPs interfacially bond to magnetite NPs (second type). The synthesis of the first type hybrid nanoparticles was carried out as follows: Magnetite nanoparticles with an average diameter of 9±2 nm were obtained by co-precipitation of iron (II, III) chlorides then they were covered with gold shell by iterative reduction of hydrogen tetrachloroaurate with hydroxylamine hydrochloride. According to the TEM, ICP MS and EDX data, final nanoparticles had an average diameter of 31±4 nm and contained iron even after hydrochloric acid treatment. However, iron signals (K-line, 7,1 keV) were not localized so we can’t speak about one single magnetic core. Described nanoparticles covered with mercapto-PEG acid were non-toxic for human prostate cancer PC-3/ LNCaP cell lines (more than 90% survived cells as compared to control) and had high R2-relaxivity rates (>190 mМ-1s-1) that exceed the transverse relaxation rate of commercial MRI-contrasting agents. These nanoparticles were also used for chymotrypsin enzyme immobilization. The effect of alternating magnetic field on catalytic properties of chymotrypsin immobilized on magnetite nanoparticles, notably the slowdown of catalyzed reaction at the level of 35-40 % was found. The synthesis of the second type hybrid nanoparticles also involved two steps. Firstly, spherical gold nanoparticles with an average diameter of 9±2 nm were synthesized by the reduction of hydrogen tetrachloroaurate with oleylamine; secondly, they were used as seeds during magnetite synthesis by thermal decomposition of iron pentacarbonyl in octadecene. As a result, so-called dumbbell-like structures were obtained where magnetite (cubes with 25±6 nm diagonal) and gold nanoparticles were connected together pairwise. By HRTEM method (first time for this type of structure) an epitaxial growth of magnetite nanoparticles on gold surface with co-orientation of (111) planes was discovered. These nanoparticles were transferred into water by means of block-copolymer Pluronic F127 then loaded with anti-cancer drug doxorubicin and also PSMA-vector specific for LNCaP cell line. Obtained nanoparticles were found to have moderate toxicity for human prostate cancer cells and got into the intracellular space after 45 minutes of incubation (according to fluorescence microscopy data). These materials are also perspective from MRI point of view (R2-relaxivity rates >70 mМ-1s-1). Thereby, in this work magnetite-gold hybrid nanoparticles, which have a strong potential for biomedical application, particularly in targeted drug delivery and magnetic resonance imaging, were synthesized and characterized. That paves the way to the development of special medicine types – theranostics. The authors knowledge financial support from Ministry of Education and Science of the Russian Federation (14.607.21.0132, RFMEFI60715X0132). This work was also supported by Grant of Ministry of Education and Science of the Russian Federation К1-2014-022, Grant of Russian Scientific Foundation 14-13-00731 and MSU development program 5.13.Keywords: drug delivery, magnetite-gold, MRI contrast agents, nanoparticles, toxicity
Procedia PDF Downloads 382993 Indirect Genotoxicity of Diesel Engine Emission: An in vivo Study Under Controlled Conditions
Authors: Y. Landkocz, P. Gosset, A. Héliot, C. Corbière, C. Vendeville, V. Keravec, S. Billet, A. Verdin, C. Monteil, D. Préterre, J-P. Morin, F. Sichel, T. Douki, P. J. Martin
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Air Pollution produced by automobile traffic is one of the main sources of pollutants in urban atmosphere and is largely due to exhausts of the diesel engine powered vehicles. The International Agency for Research on Cancer, which is part of the World Health Organization, classified in 2012 diesel engine exhaust as carcinogenic to humans (Group 1), based on sufficient evidence that exposure is associated with an increased risk for lung cancer. Amongst the strategies aimed at limiting exhausts in order to take into consideration the health impact of automobile pollution, filtration of the emissions and use of biofuels are developed, but their toxicological impact is largely unknown. Diesel exhausts are indeed complex mixtures of toxic substances difficult to study from a toxicological point of view, due to both the necessary characterization of the pollutants, sampling difficulties, potential synergy between the compounds and the wide variety of biological effects. Here, we studied the potential indirect genotoxicity of emission of Diesel engines through on-line exposure of rats in inhalation chambers to a subchronic high but realistic dose. Following exposure to standard gasoil +/- rapeseed methyl ester either upstream or downstream of a particle filter or control treatment, rats have been sacrificed and their lungs collected. The following indirect genotoxic parameters have been measured: (i) telomerase activity and telomeres length associated with rTERT and rTERC gene expression by RT-qPCR on frozen lungs, (ii) γH2AX quantification, representing double-strand DNA breaks, by immunohistochemistry on formalin fixed-paraffin embedded (FFPE) lung samples. These preliminary results will be then associated with global cellular response analyzed by pan-genomic microarrays, monitoring of oxidative stress and the quantification of primary DNA lesions in order to identify biological markers associated with a potential pro-carcinogenic response of diesel or biodiesel, with or without filters, in a relevant system of in vivo exposition.Keywords: diesel exhaust exposed rats, γH2AX, indirect genotoxicity, lung carcinogenicity, telomerase activity, telomeres length
Procedia PDF Downloads 390992 Modeling Local Warming Trend: An Application of Remote Sensing Technique
Authors: Khan R. Rahaman, Quazi K. Hassan
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Global changes in climate, environment, economies, populations, governments, institutions, and cultures converge in localities. Changes at a local scale, in turn, contribute to global changes as well as being affected by them. Our hypothesis is built on a consideration that temperature does vary at local level (i.e., termed as local warming) in comparison to the predicted models at the regional and/or global scale. To date, the bulk of the research relating local places to global climate change has been top-down, from the global toward the local, concentrating on methods of impact analysis that use as a starting point climate change scenarios derived from global models, even though these have little regional or local specificity. Thus, our focus is to understand such trends over the southern Alberta, which will enable decision makers, scientists, researcher community, and local people to adapt their policies based on local level temperature variations and to act accordingly. Specific objectives in this study are: (i) to understand the local warming (temperature in particular) trend in context of temperature normal during the period 1961-2010 at point locations using meteorological data; (ii) to validate the data by using specific yearly data, and (iii) to delineate the spatial extent of the local warming trends and understanding influential factors to adopt situation by local governments. Existing data has brought the evidence of such changes and future research emphasis will be given to validate this hypothesis based on remotely sensed data (i.e. MODIS product by NASA).Keywords: local warming, climate change, urban area, Alberta, Canada
Procedia PDF Downloads 346991 Evaluation of the Influence of Graphene Oxide on Spheroid and Monolayer Culture under Flow Conditions
Authors: A. Zuchowska, A. Buta, M. Mazurkiewicz-Pawlicka, A. Malolepszy, L. Stobinski, Z. Brzozka
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In recent years, graphene-based materials are finding more and more applications in biological science. As a thin, tough, transparent and chemically resistant materials, they appear to be a very good material for the production of implants and biosensors. Interest in graphene derivatives also resulted at the beginning of research about the possibility of their application in cancer therapy. Currently, the analysis of their potential use in photothermal therapy and as a drug carrier is mostly performed. Moreover, the direct anticancer properties of graphene-based materials are also tested. Nowadays, cytotoxic studies are conducted on in vitro cell culture in standard culture vessels (macroscale). However, in this type of cell culture, the cells grow on the synthetic surface in static conditions. For this reason, cell culture in macroscale does not reflect in vivo environment. The microfluidic systems, called Lab-on-a-chip, are proposed as a solution for improvement of cytotoxicity analysis of new compounds. Here, we present the evaluation of cytotoxic properties of graphene oxide (GO) on breast, liver and colon cancer cell line in a microfluidic system in two spatial models (2D and 3D). Before cell introduction, the microchambers surface was modified by the fibronectin (2D, monolayer) and poly(vinyl alcohol) (3D, spheroids) covering. After spheroid creation (3D) and cell attachment (2D, monolayer) the selected concentration of GO was introduced into microsystems. Then monolayer and spheroids viability/proliferation using alamarBlue® assay and standard microplate reader was checked for three days. Moreover, in every day of the culture, the morphological changes of cells were determined using microscopic analysis. Additionally, on the last day of the culture differential staining using Calcein AM and Propidium iodide were performed. We were able to note that the GO has an influence on all tested cell line viability in both monolayer and spheroid arrangement. We showed that GO caused higher viability/proliferation decrease for spheroids than a monolayer (this was observed for all tested cell lines). Higher cytotoxicity of GO on spheroid culture can be caused by different geometry of the microchambers for 2D and 3D cell cultures. Probably, GO was removed from the flat microchambers for 2D culture. Those results were also confirmed by differential staining. Comparing our results with the studies conducted in the macroscale, we also proved that the cytotoxic properties of GO are changed depending on the cell culture conditions (static/ flow).Keywords: cytotoxicity, graphene oxide, monolayer, spheroid
Procedia PDF Downloads 125990 Nanoliposomes in Photothermal Therapy: Advancements and Applications
Authors: Mehrnaz Mostafavi
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Nanoliposomes, minute lipid-based vesicles at the nano-scale, show promise in the realm of photothermal therapy (PTT). This study presents an extensive overview of nanoliposomes in PTT, exploring their distinct attributes and the significant progress in this therapeutic methodology. The research delves into the fundamental traits of nanoliposomes, emphasizing their adaptability, compatibility with biological systems, and their capacity to encapsulate diverse therapeutic substances. Specifically, it examines the integration of light-absorbing materials, like gold nanoparticles or organic dyes, into nanoliposomal formulations, enabling their efficacy as proficient agents for photothermal treatment Additionally, this paper elucidates the mechanisms involved in nanoliposome-mediated PTT, highlighting their capability to convert light energy into localized heat, facilitating the precise targeting of diseased cells or tissues. This precise regulation of light absorption and heat generation by nanoliposomes presents a non-invasive and precisely focused therapeutic approach, particularly in conditions like cancer. The study explores advancements in nanoliposomal formulations aimed at optimizing PTT outcomes. These advancements include strategies for improved stability, enhanced drug loading, and the targeted delivery of therapeutic agents to specific cells or tissues. Furthermore, the paper discusses multifunctional nanoliposomal systems, integrating imaging components or targeting elements for real-time monitoring and improved accuracy in PTT. Moreover, the review highlights recent preclinical and clinical trials showcasing the effectiveness and safety of nanoliposome-based PTT across various disease models. It also addresses challenges in clinical implementation, such as scalability, regulatory considerations, and long-term safety assessments. In conclusion, this paper underscores the substantial potential of nanoliposomes in advancing PTT as a promising therapeutic approach. Their distinctive characteristics, combined with their precise ability to convert light into heat, offer a tailored and efficient method for treating targeted diseases. The encouraging outcomes from preclinical studies pave the way for further exploration and potential clinical applications of nanoliposome-based PTT.Keywords: nanoliposomes, photothermal therapy, light absorption, heat conversion, therapeutic agents, targeted delivery, cancer therapy
Procedia PDF Downloads 112989 Audit on Antibiotic Prophylaxis and Post-Procedure Complication Rate for Patients Undergoing Transperineal Template Biopsies of the Prostate
Authors: W. Hajuthman, R. Warner, S. Rahman, M. Abraham, H. Helliwell, D. Bodiwala
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Context: Prostate cancer is a prevalent cancer in males in Europe and the US, with diagnosis primarily relying on PSA testing, mpMRI, and subsequent biopsies. However, this diagnostic strategy may lead to complications for patients. Research Aim: The aim of this study is to assess compliance with trust guidelines for antibiotic prophylaxis in patients undergoing transperineal template biopsies of the prostate and evaluate the rate of post-procedure complications. Methodology: This study is conducted retrospectively over an 8-month period. Data collection includes patient demographics, compliance with trust guidelines, associated risk factors, and post-procedure complications such as infection, haematuria, and urinary retention. Findings: The audit includes 100 patients with a median age of 66.11. The compliance with pre-procedure antibiotics was 98%, while compliance with antibiotic prophylaxis recommended by trust guidelines was 68%. Among the patients, 3% developed post-procedure sepsis, with 2 requiring admission for intravenous antibiotics. No evident risk factors were identified in these cases. Additionally, post-procedure urinary retention occurred in 3% of patients and post-procedure haematuria in 2%. Theoretical Importance: This study highlights the increasing use of transperineal template biopsies across UK centres and suggests that having a standardized protocol and compliance with guidelines can reduce confusion, ensure appropriate administration of antibiotics, and mitigate post-procedure complications. Data Collection and Analysis Procedures: Data for this study is collected retrospectively, involving the extraction and analysis of relevant information from patient records over the specified 8-month period. Question Addressed: This study addresses the following research questions: (1) What is the compliance rate with trust guidelines for antibiotic prophylaxis in transperineal template biopsies of the prostate? (2) What is the rate of post-procedure complications, such as infection, haematuria, and urinary retention? Conclusion: Transperineal template biopsies are becoming increasingly prevalent in the UK. Implementing a standardized protocol and ensuring compliance with guidelines can reduce confusion, ensure proper administration of antibiotics, and potentially minimize post-procedure complications. Additionally, considering that studies show no difference in outcomes when prophylactic antibiotics are not used, the reminder to follow trust guidelines may prompt a re-evaluation of antibiotic prescribing practices.Keywords: prostate, transperineal template biopsies of prostate, antibiotics, complications, microbiology, guidelines
Procedia PDF Downloads 79988 Development of an Aptamer-Molecularly Imprinted Polymer Based Electrochemical Sensor to Detect Pathogenic Bacteria
Authors: Meltem Agar, Maisem Laabei, Hannah Leese, Pedro Estrela
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Pathogenic bacteria and the diseases they cause have become a global problem. Their early detection is vital and can only be possible by detecting the bacteria causing the disease accurately and rapidly. Great progress has been made in this field with the use of biosensors. Molecularly imprinted polymers have gain broad interest because of their excellent properties over natural receptors, such as being stable in a variety of conditions, inexpensive, biocompatible and having long shelf life. These properties make molecularly imprinted polymers an attractive candidate to be used in biosensors. In this study it is aimed to produce an aptamer-molecularly imprinted polymer based electrochemical sensor by utilizing the properties of molecularly imprinted polymers coupled with the enhanced specificity offered by DNA aptamers. These ‘apta-MIP’ sensors were used for the detection of Staphylococcus aureus and Escherichia coli. The experimental parameters for the fabrication of sensor were optimized, and detection of the bacteria was evaluated via Electrochemical Impedance Spectroscopy. Sensitivity and selectivity experiments were conducted. Furthermore, molecularly imprinted polymer only and aptamer only electrochemical sensors were produced separately, and their performance were compared with the electrochemical sensor produced in this study. Aptamer-molecularly imprinted polymer based electrochemical sensor showed good sensitivity and selectivity in terms of detection of Staphylococcus aureus and Escherichia coli. The performance of the sensor was assessed in buffer solution and tap water.Keywords: aptamer, electrochemical sensor, staphylococcus aureus, molecularly imprinted polymer
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