Search results for: active snubber cell
5485 Lentiviral-Based Novel Bicistronic Therapeutic Vaccine against Chronic Hepatitis B Induces Robust Immune Response
Authors: Mohamad F. Jamiluddin, Emeline Sarry, Ana Bejanariu, Cécile Bauche
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Introduction: Over 360 million people are chronically infected with hepatitis B virus (HBV), of whom 1 million die each year from HBV-associated liver cirrhosis or hepatocellular carcinoma. Current treatment options for chronic hepatitis B depend on interferon-α (IFNα) or nucleos(t)ide analogs, which control virus replication but rarely eliminate the virus. Treatment with PEG-IFNα leads to a sustained antiviral response in only one third of patients. After withdrawal of the drugs, the rebound of viremia is observed in the majority of patients. Furthermore, the long-term treatment is subsequently associated with the appearance of drug resistant HBV strains that is often the cause of the therapy failure. Among the new therapeutic avenues being developed, therapeutic vaccine aimed at inducing immune responses similar to those found in resolvers is of growing interest. The high prevalence of chronic hepatitis B necessitates the design of better vaccination strategies capable of eliciting broad-spectrum of cell-mediated immunity(CMI) and humoral immune response that can control chronic hepatitis B. Induction of HBV-specific T cells and B cells by therapeutic vaccination may be an innovative strategy to overcome virus persistence. Lentiviral vectors developed and optimized by THERAVECTYS, due to their ability to transduce non-dividing cells, including dendritic cells, and induce CMI response, have demonstrated their effectiveness as vaccination tools. Method: To develop a HBV therapeutic vaccine that can induce a broad but specific immune response, we generated recombinant lentiviral vector carrying IRES(Internal Ribosome Entry Site)-containing bicistronic constructs which allow the coexpression of two vaccine products, namely HBV T- cell epitope vaccine and HBV virus like particle (VLP) vaccine. HBV T-cell epitope vaccine consists of immunodominant cluster of CD4 and CD8 epitopes with spacer in between them and epitopes are derived from HBV surface protein, HBV core, HBV X and polymerase. While HBV VLP vaccine is a HBV core protein based chimeric VLP with surface protein B-cell epitopes displayed. In order to evaluate the immunogenicity, mice were immunized with lentiviral constructs by intramuscular injection. The T cell and antibody immune responses of the two vaccine products were analyzed using IFN-γ ELISpot assay and ELISA respectively to quantify the adaptive response to HBV antigens. Results: Following a single administration in mice, lentiviral construct elicited robust antigen-specific IFN-γ responses to the encoded antigens. The HBV T- cell epitope vaccine demonstrated significantly higher T cell immunogenicity than HBV VLP vaccine. Importantly, we demonstrated by ELISA that antibodies are induced against both HBV surface protein and HBV core protein when mice injected with vaccine construct (p < 0.05). Conclusion: Our results highlight that THERAVECTYS lentiviral vectors may represent a powerful platform for immunization strategy against chronic hepatitis B. Our data suggests the likely importance of Lentiviral vector based novel bicistronic construct for further study, in combination with drugs or as standalone antigens, as a therapeutic lentiviral based HBV vaccines. THERAVECTYS bicistronic HBV vaccine will be further evaluated in animal efficacy studies.Keywords: chronic hepatitis B, lentiviral vectors, therapeutic vaccine, virus-like particle
Procedia PDF Downloads 3345484 Chemotactic Behaviour of Human Mesenchymal Stem Cells in Response to Silicate Substituted Hydroxyapatite
Authors: Dinara Ikramova, Karin A. Hing, Simon C. F. Rawlinson
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Silicate-substituted hydroxyapatite (SiHA) has been shown to enhance bone regeneration in vivo compared with phase pure stoichiometric hydroxyapatite. Evidence suggests that substrate chemistry dependent formation of a permissive protein layer on the surface of synthetic bone graft substitute materials is key for bioactivity and cell attachment. However, little information is available on whether the substrate chemistry may affect cell migration and recruitment. The aim of this study is to investigate whether or not human Mesenchymal Stem Cells (hMSCs) exhibit a chemotactic response to SiHA porous granules and if it can be linked to either the ion exchange or protein sequestering and enrichment on the surface of the material. 150mg of SiHA granules with 80% total porosity and 20% strut porosity were incubated in 1ml of either Serum Free Media (SFM) or 10% Serum Containing Media (SCM) under static cell culture conditions (37°C, 5% CO2) in absence of cells. Protein sequestering and exchange of calcium, phosphate and silicate ions were analysed at 0.5, 1, 2, 4, 8, 16 and 24 hours with n=12 per time point. Migration of hMSCs in the presence of 150mg of SiHA granules was assessed over 24 hours using a modified transwell migration system in either SFM or SCM (n=6) with 30% serum containing media acting as a positive control. At 24 hours protein sequestering and ionic exchange were analysed, and the number of cells was quantified using a high throughput confocal microscope (IN Cell Analyser 6000). In acellular condition, both calcium and phosphate ion concentrations in media showed a decrease at 24 hours which was greater in SFM than in SCM. This suggests possible formation and precipitation of a bone like apatite on the surface of SiHA. Reduction in this activity observed in SCM indicates that the presence of serum proteins is interfering with the ion exchange at the material and media interface. Adsorbed protein levels showed fluctuation over time followed by sharp decrease at 24 hours, suggesting a possible protein rearrangement on the surface of the material. The ion analysis performed on SFM and SCM after 24-hour incubation with cells in the presence of granules showed a greater reduction in phosphate concentration in both SFM and SCM compared to phosphate levels in acellular condition. Silicate concentration in SCM increased from 1.6mM (absence of cells) to 5.1mM (presence of cells). This indicates that the cells are promoting the uptake of phosphate and release of silicate ions. No significant change was seen in levels of adsorbed proteins in the presence and absence of cells. Further analysis is required to determine whether the species of these proteins change over time. The analysis of cell migration after 24-hour incubation showed more cells migrating towards the granules, 12.7% in SFM and 8.3% in SCM, than in positive control, 4.5% in SFM and 3.6% in SCM respectively. These results suggest that SiHA has a chemotactic activity independent of serum proteins. A property which has not previously been demonstrated for a synthetic bone graft material.Keywords: cell migration, hMSCs, SiHA, transwell migration system
Procedia PDF Downloads 1315483 Bacterio-Algal Microbial Fuel Cells for Sustainable Power Production, Wastewater Treatment, and Desalination
Authors: Ann D. Christy, Beenish Saba
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The Microbial fuel Cell (MFC) is a successful integrated technology for power production and wastewater treatment. MFCs are recognized for their dual function, but research in this field is still ongoing to increase efficiency and power output. One such effort is successful integration of phototrophic and autotrophic microorganisms to create bacterio-algal MFCs for sustainable electricity production along with wastewater treatment and algal biomass production. An MFC is typically configured with an anaerobic anodic chamber containing exoelectrogenic microorganisms separated by a cation exchange membrane from an adjacent aerobic cathodic chamber. The two electrodes are connected by an external circuit. This conventional MFC can be converted into a phototrophic MFC by introducing photosynthetic microorganisms into the cathode chamber. This study examines adding a third desalination chamber to a two-chamber bacterio-algal MFC. Successful results have been observed from these three-chamber MFCs demonstrating wastewater treatment in the anodic chamber, phototrophic algal growth in the cathodic chamber, and desalination in the middle chamber. The present article will summarize successful results of the bacterio-algal fuel cells and offer insights about the mechanisms involved. Tables summarizing the input substrate along with optimized operational conditions and output performance in terms of power production and efficiencies of water and wastewater treatment will be presented. The negative impacts and challenges will be discussed, along with possible future research directions. Results suggest that the three chamber bacterio-algal desalination cell has potential as a feasible technology for power production, wastewater treatment and desalination, but it needs further investigation under optimized conditions.Keywords: bacterio-algal MFC, three chamber, microbial fuel cell, wastewater treatment and desalination
Procedia PDF Downloads 3625482 Investigation of Alumina Membrane Coated Titanium Implants on Osseointegration
Authors: Pinar Erturk, Sevde Altuntas, Fatih Buyukserin
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In order to obtain an effective integration between an implant and a bone, implant surfaces should have similar properties to bone tissue surfaces. Especially mimicry of the chemical, mechanical and topographic properties of the implant to the bone is crucial for fast and effective osseointegration. Titanium-based biomaterials are more preferred in clinical use, and there are studies of coating these implants with oxide layers that have chemical/nanotopographic properties stimulating cell interactions for enhanced osseointegration. There are low success rates of current implantations, especially in craniofacial implant applications, which are large and vital zones, and the oxide layer coating increases bone-implant integration providing long-lasting implants without requiring revision surgery. Our aim in this study is to examine bone-cell behavior on titanium implants with an aluminum oxide layer (AAO) on effective osseointegration potential in the deformation of large zones with difficult spontaneous healing. In our study, aluminum layer coated titanium surfaces were anodized in sulfuric, phosphoric, and oxalic acid, which are the most common used AAO anodization electrolytes. After morphologic, chemical, and mechanical tests on AAO coated Ti substrates, viability, adhesion, and mineralization of adult bone cells on these substrates were analyzed. Besides with atomic layer deposition (ALD) as a sensitive and conformal technique, these surfaces were coated with pure alumina (5 nm); thus, cell studies were performed on ALD-coated nanoporous oxide layers with suppressed ionic content too. Lastly, in order to investigate the effect of the topography on the cell behavior, flat non-porous alumina layers on silicon wafers formed by ALD were compared with the porous ones. Cell viability ratio was similar between anodized surfaces, but pure alumina coated titanium and anodized surfaces showed a higher viability ratio compared to bare titanium and bare anodized ones. Alumina coated titanium surfaces, which anodized in phosphoric acid, showed significantly different mineralization ratios after 21 days over other bare titanium and titanium surfaces which anodized in other electrolytes. Bare titanium was the second surface that had the highest mineralization ratio. Otherwise, titanium, which is anodized in oxalic acid electrolyte, demonstrated the lowest mineralization. No significant difference was shown between bare titanium and anodized surfaces except AAO titanium surface anodized in phosphoric acid. Currently, osteogenic activities of these cells on the genetic level are investigated by quantitative real-time polymerase chain reaction (qRT-PCR) analysis results of RUNX-2, VEGF, OPG, and osteopontin genes. Also, as a result of the activities of the genes mentioned before, Western Blot will be used for protein detection. Acknowledgment: The project is supported by The Scientific and Technological Research Council of Turkey.Keywords: alumina, craniofacial implant, MG-63 cell line, osseointegration, oxalic acid, phosphoric acid, sulphuric acid, titanium
Procedia PDF Downloads 1315481 D-Lysine Assisted 1-Ethyl-3-(3-Dimethylaminopropyl)Carbodiimide / N-Hydroxy Succinimide Initiated Crosslinked Collagen Scaffold with Controlled Structural and Surface Properties
Authors: G. Krishnamoorthy, S. Anandhakumar
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The effect of D-Lysine (D-Lys) on collagen with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide(EDC)/N-hydroxysuccinimide(NHS) initiated cross linking using experimental and modelling tools are evaluated. The results of the Coll-D-Lys-EDC/NHS scaffold also indicate an increase in the tensile strength (TS), percentage of elongation (% E), denaturation temperature (Td), and decrease the decomposition rate compared to L-Lys-EDC/NHS. Scanning electron microscopic (SEM) and atomic force microscopic (AFM) analyses revealed a well ordered with properly oriented and well-aligned structure of scaffold. The D-Lys stabilizes the scaffold against degradation by collagenase than L-Lys. The cell assay showed more than 98% fibroblast viability (NIH3T3) and improved cell adhesions, protein adsorption after 72h of culture when compared with native scaffold. Cell attachment after 74h was robust, with cytoskeletal analysis showing that the attached cells were aligned along the fibers assuming a spindle-shape appearance, despite, gene expression analyses revealed no apparent alterations in mRNA levels, although cell proliferation was not adversely affected. D-Lysine (D-Lys) plays a pivotal role in the self-assembly and conformation of collagen fibrils. The D-Lys assisted EDC/NHS initiated cross-linking induces the formation of an carboxamide by the activation of the side chain -COOH group, followed by aminolysis of the O-iso acylurea intermediates by the -NH2 groups are directly joined via an isopeptides bond. This leads to the formation of intra- and inter-helical cross links. Modeling studies indicated that D-Lys bind with collagen-like peptide (CLP) through multiple H-bonding and hydrophobic interactions. Orientational changes in collagenase on CLP-D-Lys are observed which may decrease its accessibility to degradation and stabilize CLP against the action of the former. D-Lys has lowest binding energy and improved fibrillar-assembly and staggered alignment without the undesired structural stiffness and aggregations. The proteolytic machinery is not well equipped to deal with Coll-D-Lys than Coll-L-Lys scaffold. The information derived from the present study could help in designing collagenolytically stable heterochiral collagen based scaffold for biomedical applications.Keywords: collagen, collagenase, collagen like peptide, D-lysine, heterochiral collagen scaffold
Procedia PDF Downloads 3915480 Choral Singers' Preference for Expressive Priming Techniques
Authors: Shawn Michael Condon
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Current research on teaching expressivity mainly involves instrumentalists. This study focuses on choral singers’ preference of priming techniques based on four methods for teaching expressivity. 112 choral singers answered the survey about their preferred methods for priming expressivity (vocal modelling, using metaphor, tapping into felt emotions, and drawing on past experiences) in three conditions (active, passive, and instructor). Analysis revealed higher preference for drawing on past experience among more experienced singers. The most preferred technique in the passive and instructor roles was vocal modelling, with metaphors and tapping into felt emotions favoured in an active role. Priming techniques are often used in combination with other methods to enhance singing technique or expressivity and are dependent upon the situation, repertoire, and the preferences of the instructor and performer.Keywords: emotion, expressivity, performance, singing, teaching
Procedia PDF Downloads 1555479 Enhancement of Growth Regulators to Callus Formation and Silymarin Content from Different Explants of Silybum marianum Seedling
Authors: M. A. Hamza, H. A. Bosila, M. A. Zewil, I. M. Harridy
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Silymarin is one active component extracted from milk thistle Silybum marianum; it is flavonoid recognized for its ability to benefit people with liver disorders and as a protective compound against liver damaging agents. For this reason, this research aims to study the effect of growth regulators (BA+NAA) and explant type (cotyledon, hypocotyl, and root) to increase the growth and active ingredients (silymarin) in callus of S. mariaum plant. The results showed that cotyledon explant which have been cultured in MS medium supplemented with BA 0.4 mg/l. +NAA 0.25 mg/l. Led to obtain the best results in callus fresh weight (1.847a) and callus dry weight (0.155a). On the other hand, the same explant (cotyledon) cultured in MS medium supplemented with BA 1.6 mg/l. + NAA 0.5 mg/l. The suitable condition to silymarin content (0.132 mg/100 mg dry weight). And also, it turned out, lack of importance of the use of hypocotyl and root in the production of callus and silymarin compared to cotyledon.Keywords: silybum, callus, tissue culture, cotyledon
Procedia PDF Downloads 1985478 Lipid-Chitosan Hybrid Nanoparticles for Controlled Delivery of Cisplatin
Authors: Muhammad Muzamil Khan, Asadullah Madni, Nina Filipczek, Jiayi Pan, Nayab Tahir, Hassan Shah, Vladimir Torchilin
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Lipid-polymer hybrid nanoparticles (LPHNP) are delivery systems for controlled drug delivery at tumor sites. The superior biocompatible properties of lipid and structural advantages of polymer can be obtained via this system for controlled drug delivery. In the present study, cisplatin-loaded lipid-chitosan hybrid nanoparticles were formulated by the single step ionic gelation method based on ionic interaction of positively charged chitosan and negatively charged lipid. Formulations with various chitosan to lipid ratio were investigated to obtain the optimal particle size, encapsulation efficiency, and controlled release pattern. Transmission electron microscope and dynamic light scattering analysis demonstrated a size range of 181-245 nm and a zeta potential range of 20-30 mV. Compatibility among the components and the stability of formulation were demonstrated with FTIR analysis and thermal studies, respectively. The therapeutic efficacy and cellular interaction of cisplatin-loaded LPHNP were investigated using in vitro cell-based assays in A2780/ADR ovarian carcinoma cell line. Additionally, the cisplatin loaded LPHNP exhibited a low toxicity profile in rats. The in-vivo pharmacokinetics study also proved a controlled delivery of cisplatin with enhanced mean residual time and half-life. Our studies suggested that the cisplatin-loaded LPHNP being a promising platform for controlled delivery of cisplatin in cancer therapy.Keywords: cisplatin, lipid-polymer hybrid nanoparticle, chitosan, in vitro cell line study
Procedia PDF Downloads 1305477 Gravity and Geodetic Control of Geodynamic Activity near Aswan Lake, Egypt
Authors: Anwar H. Radwan, Jan Mrlina, El-Sayed A. Issawy, Ali Rayan, Salah M. Mahmoud
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Geodynamic investigations in the Aswan Lake region were started after the M=5.5 earthquake in 1981, triggered by the lake water fluctuations. Besides establishing the seismological networks, also the geodetic observations focused on the Kalabsha and Sayal fault zones were started. It was found that the Kalabsha fault is an active dextral strike-slip with normal component indicating uplift on its southern side. However, the annual velocity rates in both components do not exceed 2 mm/y, and do not therefore represent extremely active faulting. We also launched gravity monitoring in 1997, and performed another two campaigns in 2000 and 2002. The observed non- tidal temporal gravity changes indicate rather the flood water infiltration into the porous Nubian sandstone, than tectonic stress effect. The station nearest to the lake exhibited about 60 μGal positive gravity change within the 1997-2002 period.Keywords: gravity monitoring, surface movements, Lake Aswan, groundwater change
Procedia PDF Downloads 5015476 Influence of Elicitors on Callus Growth and Active Ingredient in Echinacea purpurea
Authors: Mohamed Abdelfattah Meawad Hamza, H. A. Bosila, M. A. Zewil
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This research aims to study the effect of different sources of elicitors for increase growth and active ingredients in callus of Echinacea purpurea plant. Callus that have been obtained from leaf explant, was used to conduct the following studies. A study of the impact of both the phenylalanine and tyrosine (50, 100,150 and 200 mg/l.) individually and casein hydrolysate (100, 200 and 300 mg/l.) supplemented to MS medium. Results show that Casein hydrolysate 100 mg/l. has achieved the better results in both callus fresh weight 1.881 g/explant after 8 weeks of the incubation period and callus growth rate 0.398 g/explant after 6 weeks of the incubation period, while gave add 200 mg/l. The best results in total carbohydrate 2.444 mg/ 100 mg dry weight. Phenylalanine 150 mg/l. has achieved the best results in callus dry weight 0.156 g/explant after 8 weeks of incubation period. Tyrosine 200 mg/l. recorded the best result for positive production of caffeic acid 0.460 mg/ 100 mg dry weight after 4 weeks incubation period.Keywords: tissue culture, echinacea, tyrosine, casein
Procedia PDF Downloads 2735475 A Case Study Approach on Co-Constructing the Idea of 'Safety' with Children
Authors: Beng Zhen Yeow
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In most work that involves children, the voice of the children is often not heard. This is ironic since a lot of discussions might involve their welfare and safety. It might seem natural that the professionals should hear from them about what they wish for instead of deciding what is best for them. However, this, unfortunately, might be more the exception than the norm in most case and hence in many instances, children are merely 'subjects' in conversations about safety instead of active participants in the construction or creation of safety in the family. There might be many reasons why it does not happen in our work. Firstly, professionals have learnt how to 'socialise' into their professional roles and hence in the process become 'un-childlike'. Secondly, there is also a lack of professional training with regards to how to talk with children. Finally, there might be also a lack of concrete tools and techniques that are developed to facilitate the process. In this paper, the case study method is used to show how the idea of safety could be concretised and discussed with children and their family members, and hence making them active participants and co-creators of their own safety. Specific skills and techniques are highlighted through the case study. In this case, there was improvement in outcomes like no repeated offence or abuse. In addition, children were also able to advocate for their own safety after six months of intervention and how the family members were able to explicitly say what they can do to improve safety. The professionals in the safety network reported significant improvements. On top of that, the abused child who was removed due to child protection concerns, had verbalized observations of change in mother’s parenting abilities, and has requested for home leave to begin due to ownership of safety planning and having confidence to co-create safety for her siblings and herself together with the professionals in the safety network. Children becoming active participants in the co-creation of safety not only serve the purpose in allowing them to own a 'voice' but at the same time, give them greater confidence to protect themselves at home and in other contexts outside of home.Keywords: partnering for safety, collaborative social work, family and systemic psychotherapy, child protection
Procedia PDF Downloads 1205474 Genotyping of G/P No Typable Group a Rotavirus Strains Revealed G2 and G9 Genotype Circulations in Moroccan Children Fully Vaccinated with Rotarix™
Authors: H. Boulahyaoui, S. Alaoui Amine, C. Loutfi, H. El Annaz, N. Touil, El M. El Fahim, S. Mrani
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Three Moroccan children fully vaccinated with Rotarix™ have been hospitalized for Rotavirus Gastroenteritis (RVGE) in the pediatric division of the Farabi Hospital, Oujda. Rotavirus G/P genotypes could not be typed because of their delayed crossing threshold (Ct) resolute with a group A rotavirus (RVA) real time RT-PCR. These strains were adapted to cell culture. All viruses replicated and caused extensive cytopathic effects after four or five passages in MA104 cell lines. Significant improvements have been obtained in the amount of viral particles. Each virus multiplied to a high titer (7.5 TCID50/ml). VP7 and VP4 partial gene sequencing revealed distinct genotypes compared to the Rotarix(®) vaccine strain. Two strains were of G2P[4] genotype whereas the third was G9P[8] genotype. Virus isolation while labor intensive, is recommended as a second test, especially when higher sensitivity for conventional RVA genotyping RT-PCR is needed. VP7 antigenic similarities between these strains and Rotarix were determined.Keywords: esacpe-vaccine, Morocco, Rotarix, G2P[4], G9P[8]
Procedia PDF Downloads 3335473 Smart Surveillance with 5G: A Performance Study in Adama City
Authors: Shenko Chura Aredo, Hailu Belay, Kevin T. Kornegay
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In light of Adama City’s smart city development vision, this study thoroughly investigates the performance of smart security systems with Fifth Generation (5G) network capabilities. It can be logistically difficult to install a lot of cabling, particularly in big or dynamic settings. Moreover, latency issues might affect linked systems, making it difficult for them to monitor in real time. Through a focused analysis that employs Adama City as a case study, the performance has been evaluated in terms of spectrum and energy efficiency using empirical data and basic signal processing formulations at different frequency resources. The findings also demonstrate that cameras working at higher 5G frequencies have more capacity than those operating at sub-6 GHz, notwithstanding frequency-related issues. It has also been noted that when the beams of such cameras are adaptively focussed based on the distance of the last cell edge user rather than the maximum cell radius, less energy is required than with conventional fixed power ramping.Keywords: 5G, energy efficiency, safety, smart security, spectral efficiency
Procedia PDF Downloads 185472 Nano-Immunoassay for Diagnosis of Active Schistosomal Infection
Authors: Manal M. Kame, Hanan G. El-Baz, Zeinab A.Demerdash, Engy M. Abd El-Moneem, Mohamed A. Hendawy, Ibrahim R. Bayoumi
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There is a constant need to improve the performance of current diagnostic assays of schistosomiasis as well as develop innovative testing strategies to meet new testing challenges. This study aims at increasing the diagnostic efficiency of monoclonal antibody (MAb)-based antigen detection assays through gold nanoparticles conjugated with specific anti-Schistosoma mansoni monoclonal antibodies. In this study, several hybidoma cell lines secreting MAbs against adult worm tegumental Schistosoma antigen (AWTA) were produced at Immunology Department of Theodor Bilharz Research Institute and preserved in liquid nitrogen. One MAb (6D/6F) was chosen for this study due to its high reactivity to schistosome antigens with highest optical density (OD) values. Gold nanoparticles (AuNPs) were functionalized and conjugated with MAb (6D/6F). The study was conducted on serum samples of 116 subjects: 71 patients with S. mansoni eggs in their stool samples group (gp 1), 25 with other parasites (gp2) and 20 negative healthy controls (gp3). Patients in gp1 were further subdivided according to egg count in their stool samples into Light infection {≤ 50 egg per gram(epg) (n= 17)}, moderate {51-100 epg (n= 33)} and severe infection {>100 epg(n= 21)}. Sandwich ELISA was performed using (AuNPs -MAb) for detection of circulating schistosomal antigen (CSA) levels in serum samples of all groups and the results were compared with that after using MAb/ sandwich ELISA system. Results Gold- MAb/ ELISA system reached a lower detection limit of 10 ng/ml compared to 85 ng/ml on using MAb/ ELISA and the optimal concentrations of AuNPs -MAb were found to be 12 folds less than that of MAb/ ELISA system for detection of CSA. The sensitivity and specificity of sandwich ELISA for detection of CSA levels using AuNPs -MAb were 100% & 97.8 % respectively compared to 87.3% &93.38% respectively on using MAb/ ELISA system. It was found that CSA was detected in 9 out of 71 S.mansoni infected patients on using AuNPs - MAb/ ELISA system and was not detected by MAb/ ELISA system. All those patients (9) was found to have an egg count below 50 epg feces (patients with light infections). ROC curve analyses revealed that sandwich ELISA using gold-MAb was an excellent diagnostic investigator that could differentiate Schistosoma patients from healthy controls, on the other hand it revealed that sandwich ELISA using MAb was not accurate enough as it could not recognize nine out of 71 patients with light infections. Conclusion Our data demonstrated that: Loading gold nanoparticles with MAb (6D/6F) increases the sensitivity and specificity of sandwich ELISA for detection of CSA, thus active (early) and light infections could be easily detected. Moreover this binding will decrease the amount of MAb consumed in the assay and lower the coast. The significant positive correlation that was detected between ova count (intensity of infection) and OD reading in sandwich ELISA using gold- MAb enables its use to detect the severity of infections and follow up patients after treatment for monitoring of cure.Keywords: Schistosomiasis, nanoparticles, gold, monoclonal antibodies, ELISA
Procedia PDF Downloads 3715471 Identification of Genomic Mutations in Prostate Cancer and Cancer Stem Cells By Single Cell RNAseq Analysis
Authors: Wen-Yang Hu, Ranli Lu, Mark Maienschein-Cline, Danping Hu, Larisa Nonn, Toshi Shioda, Gail S. Prins
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Background: Genetic mutations are highly associated with increased prostate cancer risk. In addition to whole genome sequencing, somatic mutations can be identified by aligning transcriptome sequences to the human genome. Here we analyzed bulk RNAseq and single cell RNAseq data of human prostate cancer cells and their matched non-cancer cells in benign regions from 4 individual patients. Methods: Sequencing raw reads were aligned to the reference genome hg38 using STAR. Variants were annotated using Annovar with respect to overlap gene annotation information, effect on gene and protein sequence, and SIFT annotation of nonsynonymous variant effect. We determined cancer-specific novel alleles by comparing variant calls in cancer cells to matched benign cells from the same individual by selecting unique alleles that were only detected in the cancer samples. Results: In bulk RNAseq data from 3 patients, the most common variants were the noncoding mutations at UTR3/UTR5, and the major variant types were single-nucleotide polymorphisms (SNP) including frameshift mutations. C>T transversion is the most frequently presented substitution of SNP. A total of 222 genes carrying unique exonic or UTR variants were revealed in cancer cells across 3 patients but not in benign cells. Among them, transcriptome levels of 7 genes (CITED2, YOD1, MCM4, HNRNPA2B1, KIF20B, DPYSL2, NR4A1) were significantly up or down regulated in cancer stem cells. Out of the 222 commonly mutated genes in cancer, 19 have nonsynonymous variants and 11 are damaged genes with variants including SIFT, frameshifts, stop gain/loss, and insertions/deletions (indels). Two damaged genes, activating transcription factor 6 (ATF6) and histone demethylase KDM3A are of particular interest; the former is a survival factor for certain cancer cells while the later positively activates androgen receptor target genes in prostate cancer. Further, single cell RNAseq data of cancer cells and their matched non-cancer benign cells from both primary 2D and 3D tumoroid cultures were analyzed. Similar to the bulk RNAseq data, single cell RNAseq in cancer demonstrated that the exonic mutations are less common than noncoding variants, with SNPs including frameshift mutations the most frequently presented types in cancer. Compared to cancer stem cell enriched-3D tumoroids, 2D cancer cells carried 3-times higher variants, 8-times more coding mutations and 10-times more nonsynonymous SNP. Finally, in both 2D primary and 3D tumoroid cultures, cancer stem cells exhibited fewer coding mutations and noncoding SNP or insertions/deletions than non-stem cancer cells. Summary: Our study demonstrates the usefulness of bulk and single cell RNAseaq data in identifying somatic mutations in prostate cancer, providing an alternative method in screening candidate genes for prostate cancer diagnosis and potential therapeutic targets. Cancer stem cells carry fewer somatic mutations than non-stem cancer cells due to their inherited immortal stand DNA from parental stem cells that explains their long-lived characteristics.Keywords: prostate cancer, stem cell, genomic mutation, RNAseq
Procedia PDF Downloads 185470 Spatial Distribution and Time Series Analysis of COVID-19 Pandemic in Italy: A Geospatial Perspective
Authors: Muhammad Farhan Ul Moazzam, Tamkeen Urooj Paracha, Ghani Rahman, Byung Gul Lee, Nasir Farid, Adnan Arshad
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The novel coronavirus pandemic disease (COVID-19) affected the whole globe, though there is a lack of clinical studies and its epidemiological features. But as per the observation, it has been seen that most of the COVID-19 infected patients show mild to moderate symptoms, and they get better without any medical assistance due to a better immune system to generate antibodies against the novel coronavirus. In this study, the active cases, serious cases, recovered cases, deaths and total confirmed cases had been analyzed using the geospatial inverse distance weightage technique (IDW) within the time span of 2nd March to 3rd June 2020. As of 3rd June, the total number of COVID-19 cases in Italy were 231,238, total deaths 33,310, serious cases 350, recovered cases 158,951, and active cases were 39,177, which has been reported by the Ministry of Health, Italy. March 2nd-June 3rd, 2020 a sum of 231,238 cases has been reported in Italy out of which 38.68% cases reported in the Lombardia region with a death rate of 18%, which is high from its national mortality rate followed by Emilia-Romagna (14.89% deaths), Piemonte (12.68% deaths), and Vento (10% deaths). As per the total cases in the region, the highest number of recoveries has been observed in Umbria (92.52%), followed by Basilicata (87%), Valle d'Aosta (86.85%), and Trento (84.54%). The COVID-19 evolution in Italy has been particularly found in the major urban area, i.e., Rome, Milan, Naples, Bologna, and Florence. Geospatial technology played a vital role in this pandemic by tracking infected patient, active cases, and recovered cases. Geospatial techniques are very important in terms of monitoring and planning to control the pandemic spread in the country.Keywords: COVID-19, public health, geospatial analysis, IDW, Italy
Procedia PDF Downloads 1535469 Development of Self Emulsifying Drug Delivery Systems (SEDDS) of Anticancer Agents Used in AYUSH System of Medicine for Improved Oral Bioavailability Followed by Their Pharmacological Evaluation Using Biotechnological Techniques
Authors: Meenu Mehta, Munish Garg
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The use of oral anticancer drugs from AYUSH system of medicine is widely increased among the society due to their low cost, enhanced efficacy, increased patient preference, lack of inconveniences related to infusion and they provide an opportunity to develop chronic treatment regimens. However, oral delivery of these drugs usually laid down by the limited bioavailability of the drug, which is associated with a wide variation. As most of the cytotoxic agents have a narrow therapeutic window and are dosed at or near the maximum tolerated dose, a wide variability in the bioavailability can negatively affect treatment result. It is estimated that 40% of active substances are poorly soluble in water. The improvement of bio-availability of drugs with such properties presents one of the greatest challenges in drug formulations. There are several techniques reported in literature. Among all these Self Emulsifying Drug Delivery System (SEDDS) has gained more attention due to enhanced oral bio-availability enabling a reduction in dose. Thus, SEDDS anticancer drugs will have the increased bioavailability and efficacy. These dosage form will provide societal benefit in a cost-effective manner as compared to other oral dosage forms. Present study reflects on the formulation strategies as SEDDS for oral anticancer agents of AYUSH system for enhanced bioavailability with proven efficacy by cancer cell lines.Keywords: anticancer agents, AYUSH system, bioavailability, SEDDS
Procedia PDF Downloads 3065468 Rhizome-Soaking with Plant-Derived Smoke-Water (Pdsw) And Karrikinolide Boosts the Essential-Oil Yield, Active Constituents and Leaf Physiological Parameters of Mentha Arvensis L
Authors: Sarika Singh, Moin Uddin, M. Masroor A. Khan, Aman Sobia Chishti, Sangram Singh, Urooj Hassan Bhatt
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Mentha arvensis L. (Japanese mint) is a perennial plant carrying medicinal, aromatic, antiseptic, and anaesthetic properties. Plant-derived smoke-water (PDSW) plays a significant role in seed germination, seedling growth, and other physiological attributes. To ascertain the effect of PDSW and karrikinolide on Mentha arvensis L., a rhizome-soaking experiment was conducted on Mentha arvensis. Prior to planting, mint rhizomes were soaked for 24 hours with aqueous solutions of various concentrations of PDSW (1:125v/v, 1:250 v/v, 1:500 v/v, and 1:1000 v/v), karrikinolide (10-6M, 10⁻⁷M, 10⁻⁸M, and 10⁻⁹M) using double distilled water as control treatment. Rhizome soaking with 1:500 v/v concentration of PDSW and 10⁻⁸M concentration of KAR1 increased the growth attributes, including plant height, fresh weight, dry, leaf area, and leaf yield per plant of Mentha arvensis. Leaf physiological-parameters, viz. chlorophyll fluorescence, PSII activity, and total chlorophyll and carotenoid content, were also increased as a result of the application of this treatment PDSW (1:500 v/v) and KAR1 (10⁻⁸M). In addition, treatment with 1:500 v/v and 10⁻⁸M significantly increased the essential oil yield and active constituents of Mentha arvensis compared to the control. Results indicated that PDSW, being a cheap source of karrikins, might be successfully used to augment mint essential oil production.Keywords: active constituents, essential oil, medicinal plant, mentha arvensis L
Procedia PDF Downloads 895467 Determination of the Toxicity of a Lunar Dust Simulant on Human Alveolar Epithelial Cells and Macrophages in vitro
Authors: Agatha Bebbington, Terry Tetley, Kathryn Hadler
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Background: Astronauts will set foot on the Moon later this decade, and are at high risk of lunar dust inhalation. Freshly-fractured lunar dust produces reactive oxygen species in solution, which are known to cause cellular damage and inflammation. Cytotoxicity and inflammatory mediator release was measured in pulmonary alveolar epithelial cells (cells that line the gas-exchange zone of the lung) exposed to a lunar dust simulant, LMS-1. It was hypothesised that freshly-fractured LMS-1 would result in increased cytotoxicity and inflammatory mediator release, owing to the angular morphology and high reactivity of fractured particles. Methods: A human alveolar epithelial type 1-like cell line (TT1) and a human macrophage-like cell line (THP-1) were exposed to 0-200μg/ml of unground, aged-ground, and freshly-ground LMS-1 (screened at <22μm). Cell viability, cytotoxicity, and inflammatory mediator release (IL-6, IL-8) were assessed using MMT, LDH, and ELISA assays, respectively. LMS-1 particles were characterised for their size, surface area, and morphology before and after grinding. Results: Exposure to LMS-1 particles did not result in overt cytotoxicity in either TT1 epithelial cells or THP-1 macrophage-like cells. A dose-dependent increase in IL-8 release was observed in TT1 cells, whereas THP-1 cell exposure, even at low particle concentrations, resulted in increased IL-8 release. Both cytotoxic and pro-inflammatory responses were most marked and significantly greater in TT1 and THP-1 cells exposed to freshly-fractured LMS-1. Discussion: LMS-1 is a novel lunar dust simulant; this is the first study to determine its toxicological effects on respiratory cells in vitro. An increased inflammatory response in TT1 and THP-1 cells exposed to ground LMS-1 suggests that low particle size, increased surface area, and angularity likely contribute to toxicity. Conclusions: Evenlow levels of exposure to LMS-1 could result in alveolar inflammation. This may have pathological consequences for astronauts exposed to lunar dust on future long-duration missions. Future research should test the effect of low-dose, intermittent lunar dust exposure on the respiratory system.Keywords: lunar dust, LMS-1, lunar dust simulant, long-duration space travel, lunar dust toxicity
Procedia PDF Downloads 2145466 Hepatic Regenerative Capacity after Acetaminophen-Induced Liver Injury in Mouse Model
Authors: N. F. Hamid, A. Kipar, J. Stewart, D. J. Antoine, B. K. Park, D. P. Williams
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Acetaminophen (APAP) is a widely used analgesic that is safe at therapeutic doses. The mouse model of APAP has been extensively used for studies on pathogenesis and intervention of drug induced liver injury based on the CytP450 mediated formation of N-acetyl-p-benzo-quinoneimine and, more recently, as model for mechanism based biomarkers. Delay of the fasted CD1 mice to rebound to the basal level of hepatic GSH compare to fed mice is reported in this study. Histologically, 15 hours fasted mice prior to APAP treatment leading to overall more intense cell loss with no evidence of apoptosis as compared to non-fasted mice, where the apoptotic cells were clearly seen on cleaved caspase-3 immunostaining. After 15 hours post APAP administration, hepatocytes underwent stage of recovery with evidence of mitotic figures in fed mice and return to completely no histological difference to control at 24 hours. On the contrary, the evidence of ongoing cells damage and inflammatory cells infiltration are still present on fasted mice until the end of the study. To further measure the regenerative capacity of the hepatocytes, the inflammatory mediators of cytokines that involved in the progression or regression of the toxicity like TNF-α and IL-6 in liver and spleen using RT-qPCR were also included. Yet, quantification of proliferating cell nuclear antigen (PCNA) has demonstrated the time for hepatic regenerative in fasted is longer than that to fed mice. Together, these data would probably confirm that fasting prior to APAP treatment does not only modulate liver injury, but could have further effects to delay subsequent regeneration of the hepatocytes.Keywords: acetaminophen, liver, proliferating cell nuclear antigen, regeneration, apoptosis
Procedia PDF Downloads 4315465 Core-Shell Nanofibers for Prevention of Postsurgical Adhesion
Authors: Jyh-Ping Chen, Chia-Lin Sheu
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In this study, we propose to use electrospinning to fabricate porous nanofibrous membranes as postsurgical anti-adhesion barriers and to improve the properties of current post-surgical anti-adhesion products. We propose to combine FDA-approved biomaterials with anti-adhesion properties, polycaprolactone (PCL), polyethylene glycol (PEG), hyaluronic acid (HA) with silver nanoparticles (Ag) and ibuprofen (IBU), to produce anti-adhesion barrier nanofibrous membranes. For this purpose, PEG/PCL/Ag/HA/IBU core-shell nanofibers were prepared. The shell layer contains PEG + PCL to provide mechanical supports and Ag was added to the outer PEG-PCL shell layer during electrospinning to endow the nanofibrous membrane with anti-bacterial properties. The core contains HA to exert anti-adhesion and IBU to exert anti-inflammation effects, respectively. The nanofibrous structure of the membranes can reduce cell penetration while allowing nutrient and waste transports to prevent postsurgical adhesion. Nanofibers with different core/shell thickness ratio were prepared. The nanofibrous membranes were first characterized for their physico-chemical properties in detail, followed by in vitro cell culture studies for cell attachment and proliferation. The HA released from the core region showed extended release up to 21 days for prolonged anti-adhesion effects. The attachment of adhesion-forming fibroblasts is reduced using the nanofibrous membrane from DNA assays and confocal microscopic observation of adhesion protein vinculin expression. The Ag released from the shell showed burst release to prevent E Coli and S. aureus infection immediately and prevent bacterial resistance to Ag. Minimum cytotoxicity was observed from Ag and IBU when fibroblasts were culture with the extraction medium of the nanofibrous membranes. The peritendinous anti-adhesion model in rabbits and the peritoneal anti-adhesion model in rats were used to test the efficacy of the anti-adhesion barriers as determined by gross observation, histology, and biomechanical tests. Within all membranes, the PEG/PCL/Ag/HA/IBU core-shell nanofibers showed the best reduction in cell attachment and proliferation when tested with fibroblasts in vitro. The PEG/PCL/Ag/HA/IBU nanofibrous membranes also showed significant improvement in preventing both peritendinous and peritoneal adhesions when compared with other groups and a commercial adhesion barrier film.Keywords: anti-adhesion, electrospinning, hyaluronic acid, ibuprofen, nanofibers
Procedia PDF Downloads 1815464 A Three-Dimensional TLM Simulation Method for Thermal Effect in PV-Solar Cells
Authors: R. Hocine, A. Boudjemai, A. Amrani, K. Belkacemi
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Temperature rising is a negative factor in almost all systems. It could cause by self heating or ambient temperature. In solar photovoltaic cells this temperature rising affects on the behavior of cells. The ability of a PV module to withstand the effects of periodic hot-spot heating that occurs when cells are operated under reverse biased conditions is closely related to the properties of the cell semi-conductor material. In addition, the thermal effect also influences the estimation of the maximum power point (MPP) and electrical parameters for the PV modules, such as maximum output power, maximum conversion efficiency, internal efficiency, reliability, and lifetime. The cells junction temperature is a critical parameter that significantly affects the electrical characteristics of PV modules. For practical applications of PV modules, it is very important to accurately estimate the junction temperature of PV modules and analyze the thermal characteristics of the PV modules. Once the temperature variation is taken into account, we can then acquire a more accurate MPP for the PV modules, and the maximum utilization efficiency of the PV modules can also be further achieved. In this paper, the three-Dimensional Transmission Line Matrix (3D-TLM) method was used to map the surface temperature distribution of solar cells while in the reverse bias mode. It was observed that some cells exhibited an inhomogeneity of the surface temperature resulting in localized heating (hot-spot). This hot-spot heating causes irreversible destruction of the solar cell structure. Hot spots can have a deleterious impact on the total solar modules if individual solar cells are heated. So, the results show clearly that the solar cells are capable of self-generating considerable amounts of heat that should be dissipated very quickly to increase PV module's lifetime.Keywords: thermal effect, conduction, heat dissipation, thermal conductivity, solar cell, PV module, nodes, 3D-TLM
Procedia PDF Downloads 3875463 Psychological Aspects of Quality of Life in Patients with Primary and Metastatic Bone Tumors
Authors: O. Yu Shchelkova, E. B. Usmanova
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Introduction: Last decades scientific research of quality of life (QoL) is developing fast worldwide. QoL concept pays attention to emotional experience of disease in patients, particularly to personal sense of possibility to satisfy actual needs and possibility of full social functioning in spite of disease limitations. QoL in oncological patients is studied intensively. Nevertheless, the issue of QoL in patients with bone tumors focused on psychological factors of QoL and relation to disease impact on QoL is not discussed. The aim of the study was to reveal the basic aspects and personality factors of QoL in patients with bone tumor. Results: Study participants were 139 patients with bone tumors. The diagnoses were osteosarcoma (n=42), giant cell tumor (n=32), chondrosarcoma (n=32), Ewing sarcoma (n=10) and bone metastases (n=23). The study revealed that patients with bone metastases assess their health significantly worse than other patients. Besides patients with osteosarcoma evaluate their general health higher than patients with giant cell tumors. Social functioning in patients with chondrosarcoma is higher than in patients with bone metastases and patients with giant cell tumor. Patients with chondrosarcoma have higher physical functioning and less restricted in daily activities than patients with bone metastases. Patients with bone metastases characterize their pain as more widespread than patients with primary bone tumors and have more functional restrictions due to bone incision. Moreover, the study revealed personality significant influence on QoL related to bone tumors. Such characteristics in structure of personality as high degree of self-consciousness, personal resources, cooperation and disposition to positive reappraisal in difficult situation correspond to higher QoL. Otherwise low personal resources and slight problem solving behaviour, low degree of self-consciousness and high social dependence correspond to decrease of QoL in patients with bone tumors. Conclusion: Patients with bone metastasis have lower QoL compared to patients with primary bone tumors. Patients with giant cell tumor have the worth quality of life among patients with primary bone tumors. Furthermore, the results revealed differences in QoL parameters associated with personality characteristics in patients with bone tumors. Such psychological factors as future goals, interest in life and emotional saturation, besides high degree of personal resources and cooperation influence on increasing QoL in patients with bone tumors.Keywords: quality of life, psychological factors, bone tumor, personality
Procedia PDF Downloads 1405462 Determination of the Vaccine Induced Immunodominant Regions of Nucleoprotein Crimean-Congo Hemorrhagic Fever Virus
Authors: Engin Berber, Nurettin Canakoglu, Ibrahim Sozdutmaz, Merve Caliskan, Shaikh Terkis Islam Pavel, Hazel Yetiskin, Aykut Ozdarendeli
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Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus in the family Bunyaviridae, genus Nairovirus. The CCHFV genome consists of three molecules of negative-sense single-stranded RNA, each encapsulated separately. The virion particle contains viral RNA polymerase (L segment), surface glycoproteins Gn and Gc (Msegment), and a nucleocapsid protein NP (S segment). CCHF is characterized by high case mortality, occurring in Asia, Africa, the Middle East and Eastern Europe. Clinical CCHF was first recognized in Turkey in 2002. The numbers of CCHF cases have gradually increased in Turkey making the virus a public health concern. Between 2002 and 2014, more than 8000 the CCHF cases have been reported in Turkey and mortality rate is around 5%. So, Turkey is one of the countries where the epidemy has become spread to the wider geography and the biggest outbreaks of CCHF have occurred in the world. We have recently developed an inactivated cell-culture based vaccine against CCHF. We have showed that the Balb/c mice immunized with the CCHF vaccine induced the high level of neutralizing antibodies. In this study, we aimed to determine the immunodominant regions of nucleoprotein (NP) CCHFV Kelkit06 strain which stimulate T cells. For this purpose, pools of overlapping NP were used for an IFN- γ ELISPOT assay. Balb/c mice were divided into two groups for the experiment. Two groups (n = 10 each) were immunized via the intraperitoneal route with 5, or 10μg of the cell culture-based vaccine. The control group (n = 6) was mock immunized with PBS. Booster injections with the same formulation were given on days 21 and 42 after the first immunization. The higher reactivity against the CCHFV NP pools 31-40 and 80-90 was determined in the two dose groups. In order to analyze the vaccine-induced T cell responses in Balb/c mice immunized with varying doses of the vaccine, we have been also currently working on CD4+, CD8+ and CD3 + T cells by flow cytometry.Keywords: Crimean-Congo hemorrhagic fever virus, immunodominant regions of NP, T cell response, vaccine
Procedia PDF Downloads 3465461 Poster for Sickle Cell Disease and Barriers to Care in South Yorkshire from 2017 to 2023
Authors: Amardass Dhami, Clare Samuelson
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Background: Sickle cell disease (SCD) is a complex, multisystem condition that significantly impacts patients' quality of life, characterized by acute illness episodes, progressive organ damage, and reduced life expectancy. In the UK, over 13,000 individuals are affected, with South Yorkshire having the fifth highest prevalence, including approximately 800 patients. Retinal complications in SCD can manifest as either proliferative or non-proliferative disease, with proliferative changes being more prevalent. These retinal issues can cause significant morbidity, including visual loss and increased care requirements, underscoring the need for regular monitoring. An integrated approach was applied to ensure timely interventions, ultimately enhancing patient outcomes and reduce ‘did not attend’ rates. Aim: To assess the factors which may influence attendance to Haematology and Ophthalmology Clinics with attention towards levels of deprivation towards non-attendance. Method : A retrospective study on 84 eligible patients, from the regional tertiary Centre for Sickle Cell Care (Sheffield Teaching Hospital) from 2017 to 2023. The study focused on the incidence of sickle cell eye disease, specifically examining the outcomes of patients who attended the combined haematology and ophthalmology clinics. Patients who did not attend either clinic were excluded from the analysis to ensure a clear understanding of the combined clinic's impact. This data was then compared with the United Kingdom’s Index of Multiple Deprivation (IMD) datasets to assess if inequalities of care affected this population. Results: The study concluded that the effectiveness of combining haematology and ophthalmology clinics was reduced following the intervention. The DNA rates increased to 40% for the haematology clinic. Additionally, a significant proportion of the cohort was classified as residing in areas of deprivation, suggesting a possible link between socioeconomic factors and non-attendance rates Conclusion: These findings underscore the challenges of integrating care for SCD patients, particularly in relation to socioeconomic barriers. Despite the intent to streamline care and improve patient outcomes, the increase in DNA rates points to the need for further investigation into the underlying causes of non-attendance. Addressing these issues, especially in deprived areas, could enhance the effectiveness of combined clinics and ensure that patients receive the necessary monitoring and interventions for their eye health and overall well-being. Future strategies may need to focus on improving accessibility, outreach, and support for patients to mitigate the impact of socioeconomic factors on healthcare attendance.Keywords: south yorkshire, sickle cell anemia, deprivation, factors, haematology
Procedia PDF Downloads 135460 Development of Programmed Cell Death Protein 1 Pathway-Associated Prognostic Biomarkers for Bladder Cancer Using Transcriptomic Databases
Authors: Shu-Pin Huang, Pai-Chi Teng, Hao-Han Chang, Chia-Hsin Liu, Yung-Lun Lin, Shu-Chi Wang, Hsin-Chih Yeh, Chih-Pin Chuu, Jiun-Hung Geng, Li-Hsin Chang, Wei-Chung Cheng, Chia-Yang Li
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The emergence of immune checkpoint inhibitors (ICIs) targeting proteins like PD-1 and PD-L1 has changed the treatment paradigm of bladder cancer. However, not all patients benefit from ICIs, with some experiencing early death. There's a significant need for biomarkers associated with the PD-1 pathway in bladder cancer. Current biomarkers focus on tumor PD-L1 expression, but a more comprehensive understanding of PD-1-related biology is needed. Our study has developed a seven-gene risk score panel, employing a comprehensive bioinformatics strategy, which could serve as a potential prognostic and predictive biomarker for bladder cancer. This panel incorporates the FYN, GRAP2, TRIB3, MAP3K8, AKT3, CD274, and CD80 genes. Additionally, we examined the relationship between this panel and immune cell function, utilizing validated tools such as ESTIMATE, TIDE, and CIBERSORT. Our seven-genes panel has been found to be significantly associated with bladder cancer survival in two independent cohorts. The panel was also significantly correlated with tumor infiltration lymphocytes, immune scores, and tumor purity. These factors have been previously reported to have clinical implications on ICIs. The findings suggest the potential of a PD-1 pathway-based transcriptomic panel as a prognostic and predictive biomarker in bladder cancer, which could help optimize treatment strategies and improve patient outcomes.Keywords: bladder cancer, programmed cell death protein 1, prognostic biomarker, immune checkpoint inhibitors, predictive biomarker
Procedia PDF Downloads 785459 Design, Synthesis and Evaluation of 4-(Phenylsulfonamido)Benzamide Derivatives as Selective Butyrylcholinesterase Inhibitors
Authors: Sushil Kumar Singh, Ashok Kumar, Ankit Ganeshpurkar, Ravi Singh, Devendra Kumar
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In spectrum of neurodegenerative diseases, Alzheimer’s disease (AD) is characterized by the presence of amyloid β plaques and neurofibrillary tangles in the brain. It results in cognitive and memory impairment due to loss of cholinergic neurons, which is considered to be one of the contributing factors. Donepezil, an acetylcholinesterase (AChE) inhibitor which also inhibits butyrylcholinesterase (BuChE) and improves the memory and brain’s cognitive functions, is the most successful and prescribed drug to treat the symptoms of AD. The present work is based on designing of the selective BuChE inhibitors using computational techniques. In this work, machine learning models were trained using classification algorithms followed by screening of diverse chemical library of compounds. The various molecular modelling and simulation techniques were used to obtain the virtual hits. The amide derivatives of 4-(phenylsulfonamido) benzoic acid were synthesized and characterized using 1H & 13C NMR, FTIR and mass spectrometry. The enzyme inhibition assays were performed on equine plasma BuChE and electric eel’s AChE by method developed by Ellman et al. Compounds 31, 34, 37, 42, 49, 52 and 54 were found to be active against equine BuChE. N-(2-chlorophenyl)-4-(phenylsulfonamido)benzamide and N-(2-bromophenyl)-4-(phenylsulfonamido)benzamide (compounds 34 and 37) displayed IC50 of 61.32 ± 7.21 and 42.64 ± 2.17 nM against equine plasma BuChE. Ortho-substituted derivatives were more active against BuChE. Further, the ortho-halogen and ortho-alkyl substituted derivatives were found to be most active among all with minimal AChE inhibition. The compounds were selective toward BuChE.Keywords: Alzheimer disease, butyrylcholinesterase, machine learning, sulfonamides
Procedia PDF Downloads 1395458 The Effects of Passive and Active Recoveries on Responses of Platelet Indices and Hemodynamic Variables to Resistance Exercise
Authors: Mohammad Soltani, Sajad Ahmadizad, Fatemeh Hoseinzadeh, Atefe Sarvestan
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The exercise recovery is an important variable in designing resistance exercise training. This study determined the effects of passive and active recoveries on responses of platelet indices and hemodynamic variables to resistance exercise. Twelve healthy subjects (six men and six women, age, 25.4 ±2.5 yrs) performed two types of resistance exercise protocols (six exercises including upper- and lower-body parts) at two separate sessions with one-week intervening. First resistance protocol included three sets of six repetitions at 80% of 1RM with 2 min passive rest between sets and exercises; while, the second protocol included three sets of six repetitions at 60% of 1RM followed by active recovery included six repetitions of the same exercise at 20% of 1RM. The exercise volume was equalized. Three blood samples were taken before exercise, immediately after exercise and after 1-hour recovery, and analyzed for fibrinogen and platelet indices. Blood pressure (BP), heart rate (HR) and rate pressure product (RPP), were measured before, immediately after exercise and every 5 minutes during recovery. Data analyzes showed a significant increase in SBP (systolic blood pressure), HR, rate of pressure product (RPP) and PLT in response to resistance exercise (P<0.05) and that changes for HR and RPP were significantly different between two protocols (P<0.05). Furthermore, MPV and P_LCR did not change in response to resistance exercise, though significant reductions were observed after 1h recovery compared to before and after exercise (P<0.05). No significant changes in fibrinogen and PDW following two types of resistance exercise protocols were observed (P>0.05). On the other hand, no significant differences in platelet indices were found between the two protocols (P>0.05). Resistance exercise induces changes in platelet indices and hemodynamic variables, and that these changes are not related to the type of recovery and returned to normal levels after 1h recovery.Keywords: hemodynamic variables, platelet indices, resistance exercise, recovery intensity
Procedia PDF Downloads 1425457 Design of Robust and Intelligent Controller for Active Removal of Space Debris
Authors: Shabadini Sampath, Jinglang Feng
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With huge kinetic energy, space debris poses a major threat to astronauts’ space activities and spacecraft in orbit if a collision happens. The active removal of space debris is required in order to avoid frequent collisions that would occur. In addition, the amount of space debris will increase uncontrollably, posing a threat to the safety of the entire space system. But the safe and reliable removal of large-scale space debris has been a huge challenge to date. While capturing and deorbiting space debris, the space manipulator has to achieve high control precision. However, due to uncertainties and unknown disturbances, there is difficulty in coordinating the control of the space manipulator. To address this challenge, this paper focuses on developing a robust and intelligent control algorithm that controls joint movement and restricts it on the sliding manifold by reducing uncertainties. A neural network adaptive sliding mode controller (NNASMC) is applied with the objective of finding the control law such that the joint motions of the space manipulator follow the given trajectory. A computed torque control (CTC) is an effective motion control strategy that is used in this paper for computing space manipulator arm torque to generate the required motion. Based on the Lyapunov stability theorem, the proposed intelligent controller NNASMC and CTC guarantees the robustness and global asymptotic stability of the closed-loop control system. Finally, the controllers used in the paper are modeled and simulated using MATLAB Simulink. The results are presented to prove the effectiveness of the proposed controller approach.Keywords: GNC, active removal of space debris, AI controllers, MatLabSimulink
Procedia PDF Downloads 1325456 Synthesis and Characterization of Chiral Dopant Based on Schiff's Base Structure
Authors: Hong-Min Kim, Da-Som Han, Myong-Hoon Lee
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CLCs (Cholesteric liquid crystals) draw tremendous interest due to their potential in various applications such as cholesteric color filters in LCD devices. CLC possesses helical molecular orientation which is induced by a chiral dopant molecules mixed with nematic liquid crystals. The efficiency of a chiral dopant is quantified by the HTP (helical twisting power). In this work, we designed and synthesized a series of new chiral dopants having a Schiff’s base imine structure with different alkyl chain lengths (butyl, hexyl and octyl) from chiral naphthyl amine by two-step reaction. The structures of new chiral dopants were confirmed by 1H-NMR and IR spectroscopy. The properties were investigated by DSC (differential scanning calorimetry calorimetry), POM (polarized optical microscopy) and UV-Vis spectrophotometer. These solid state chiral dopants showed excellent solubility in nematic LC (MLC-6845-000) higher than 17wt%. We prepared the CLC(Cholesteric Liquid Crystal) cell by mixing nematic LC (MLC-6845-000) with different concentrations of chiral dopants and injecting into the sandwich cell of 5μm cell gap with antiparallel alignment. The cholesteric liquid crystal phase was confirmed from POM, in which all the samples showed planar phase, a typical phase of the cholesteric liquid crystals. The HTP (helical twisting power) is one of the most important properties of CLC. We measured the HTP values from the UV-Vis transmittance spectra of CLC cells with varies chiral dopant concentration. The HTP values with different alkyl chains are as follows: butyl chiral dopant=29.8μm-1; hexyl chiral dopant= 31.8μm-1; octyl chiral dopant=27.7μm-1. We obtained the red, green and blue reflection color from CLC cells, which can be used as color filters in LCDs applications.Keywords: cholesteric liquid crystal, color filter, display, HTP
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