Search results for: oral squamous cell carcinoma
2159 Electromagnetic-Mechanical Stimulation on PC12 for Enhancement of Nerve Axonal Extension
Authors: E. Nakamachi, K. Matsumoto, K. Yamamoto, Y. Morita, H. Sakamoto
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In recently, electromagnetic and mechanical stimulations have been recognized as the effective extracellular environment stimulation technique to enhance the defected peripheral nerve tissue regeneration. In this study, we developed a new hybrid bioreactor by adopting 50 Hz uniform alternative current (AC) magnetic stimulation and 4% strain mechanical stimulation. The guide tube for nerve regeneration is mesh structured tube made of biodegradable polymer, such as polylatic acid (PLA). However, when neural damage is large, there is a possibility that peripheral nerve undergoes necrosis. So it is quite important to accelerate the nerve tissue regeneration by achieving enhancement of nerve axonal extension rate. Therefore, we try to design and fabricate the system that can simultaneously load the uniform AC magnetic field stimulation and the stretch stimulation to cells for enhancement of nerve axonal extension. Next, we evaluated systems performance and the effectiveness of each stimulation for rat adrenal pheochromocytoma cells (PC12). First, we designed and fabricated the uniform AC magnetic field system and the stretch stimulation system. For the AC magnetic stimulation system, we focused on the use of pole piece structure to carry out in-situ microscopic observation. We designed an optimum pole piece structure using the magnetic field finite element analyses and the response surface methodology. We fabricated the uniform AC magnetic field stimulation system as a bio-reactor by adopting analytically determined design specifications. We measured magnetic flux density that is generated by the uniform AC magnetic field stimulation system. We confirmed that measurement values show good agreement with analytical results, where the uniform magnetic field was observed. Second, we fabricated the cyclic stretch stimulation device under the conditions of particular strains, where the chamber was made of polyoxymethylene (POM). We measured strains in the PC12 cell culture region to confirm the uniform strain. We found slightly different values from the target strain. Finally, we concluded that these differences were allowable in this mechanical stimulation system. We evaluated the effectiveness of each stimulation to enhance the nerve axonal extension using PC12. We confirmed that the average axonal extension length of PC12 under the uniform AC magnetic stimulation was increased by 16 % at 96 h in our bio-reactor. We could not confirm that the axonal extension enhancement under the stretch stimulation condition, where we found the exfoliating of cells. Further, the hybrid stimulation enhanced the axonal extension. Because the magnetic stimulation inhibits the exfoliating of cells. Finally, we concluded that the enhancement of PC12 axonal extension is due to the magnetic stimulation rather than the mechanical stimulation. Finally, we confirmed that the effectiveness of the uniform AC magnetic field stimulation for the nerve axonal extension using PC12 cells.Keywords: nerve cell PC12, axonal extension, nerve regeneration, electromagnetic-mechanical stimulation, bioreactor
Procedia PDF Downloads 2652158 Preoperative Parental Anxiety is not Associated with Postoperative Emergence Agitation in Children Undergoing Adenoidectomy and/or Tonsillectomy
Authors: S. Öcal, A. Erakgün, E. Yüksel, M. N. Deniz, E. Erhan, A. Çertuğ
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Background: Emergence agitation (EA) is defined as a dissociated state of consciousness during the early post-anesthesia period in which the child is inconsolable, irritable, uncompromising or uncooperative, typically thrashing, crying, moaning, or incoherent, and not recognizing or identifying familiar and known objects or people. Some studies found preoperative parental anxiety to be a predictor of EA. Methods: Seventy-four children, between the ages of 3-12 undergoing adenoidectomy/tonsillectomy at Ege University Hospital, were studied. Anesthesia was induced and maintained using 2% sevoflurane in 50% oxygen and 50% air following a premedicative dose of 0.5mg/kg oral midazolam. After the children were taken into the operating theater, the mothers were given the State-Trait Anxiety Inventory (STAI) questionnaire. To evaluate EA, Post Anesthetic Emergence Delirium (PAED) score of the children were noted every 10min during the first 30min of the postoperative period. EA was defined with a highest PAED score of ≥ 10, and non-EA with a highest PAED score of ≤ 9. Results: In this study, the incidence of postoperative EA was 31% (34% under the age of 6 and 19% over). Mothers of children with EA were found not to be significantly more anxious on STAI compared to mothers of non-EA children. Conclusions: Contrary to some earlier studies, we were unable to find an association between preoperative parental anxiety and postoperative EA.Keywords: parental anxiety, emergence agittion, Post Anesthetic Emergence Delirium, anesthesia
Procedia PDF Downloads 3432157 MANIFEST-2, a Global, Phase 3, Randomized, Double-Blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAK Inhibitor-Naïve Myelofibrosis Patients
Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas
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Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib
Procedia PDF Downloads 2012156 Alternating Current Photovoltaic Module Model
Authors: Irtaza M. Syed, Kaamran Raahemifar
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This paper presents modeling of a Alternating Current (AC) Photovoltaic (PV) module using Matlab/Simulink. The proposed AC-PV module model is simple, realistic, and application oriented. The model is derived on module level as compared to cell level directly from the information provided by the manufacturer data sheet. DC-PV module, MPPT control, BC, VSI and LC filter, all were treated as a single unit. The model accounts for changes in variations of both irradiance and temperature. The AC-PV module proposed model is simulated and the results are compared with the datasheet projected numbers to validate model’s accuracy and effectiveness. Implementation and results demonstrate simplicity and accuracy, as well as reliability of the model.Keywords: PV modeling, AC PV Module, datasheet, VI curves irradiance, temperature, MPPT, Matlab/Simulink
Procedia PDF Downloads 5752155 AAV-Mediated Human Α-Synuclein Expression in a Rat Model of Parkinson's Disease –Further Characterization of PD Phenotype, Fine Motor Functional Effects as Well as Neurochemical and Neuropathological Changes over Time
Authors: R. Pussinen, V. Jankovic, U. Herzberg, M. Cerrada-Gimenez, T. Huhtala, A. Nurmi, T. Ahtoniemi
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Targeted over-expression of human α-synuclein using viral-vector mediated gene delivery into the substantia nigra of rats and non-human primates has been reported to lead to dopaminergic cell loss and the formation of α-synuclein aggregates reminiscent of Lewy bodies. We have previously shown how AAV-mediated expression of α-synuclein is seen in the chronic phenotype of the rats over 16 week follow-up period. In the context of these findings, we attempted to further characterize this long term PD related functional and motor deficits as well as neurochemical and neuropathological changes in AAV-mediated α-synuclein transfection model in rats during chronic follow-up period. Different titers of recombinant AAV expressing human α-synuclein (A53T) were stereotaxically injected unilaterally into substantia nigra of Wistar rats. Rats were allowed to recover for 3 weeks prior to initial baseline behavioral testing with rotational asymmetry test, stepping test and cylinder test. A similar behavioral test battery was applied again at weeks 5, 9,12 and 15. In addition to traditionally used rat PD model tests, MotoRater test system, a high speed kinematic gait performance monitoring was applied during the follow-up period. Evaluation focused on animal gait between groups. Tremor analysis was performed on weeks 9, 12 and 15. In addition to behavioral end-points, neurochemical evaluation of dopamine and its metabolites were evaluated in striatum. Furthermore, integrity of the dopamine active transport (DAT) system was evaluated by using 123I- β-CIT and SPECT/CT imaging on weeks 3, 8 and 12 after AAV- α-synuclein transfection. Histopathology was examined from end-point samples at 3 or 12 weeks after AAV- α-synuclein transfection to evaluate dopaminergic cell viability and microglial (Iba-1) activation status in substantia nigra by using stereological analysis techniques. This study focused on the characterization and validation of previously published AAV- α-synuclein transfection model in rats but with the addition of novel end-points. We present the long term phenotype of AAV- α-synuclein transfected rats with traditionally used behavioral tests but also by using novel fine motor analysis techniques and tremor analysis which provide new insight to unilateral effects of AAV α-synuclein transfection. We also present data about neurochemical and neuropathological end-points for the dopaminergic system in the model and how well they correlate with behavioral phenotype.Keywords: adeno-associated virus, alphasynuclein, animal model, Parkinson’s disease
Procedia PDF Downloads 2952154 Synchrony between Genetic Repressilators in Sister Cells in Different Temperatures
Authors: Jerome G. Chandraseelan, Samuel M. D. Oliveira, Antti Häkkinen, Sofia Startceva, Andre S. Ribeiro
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We used live E. coli containing synthetic genetic oscillators to study how the degree of synchrony between the genetic circuits of sister cells changes with temperature. We found that both the mean and the variability of the degree of synchrony between the fluorescence signals from sister cells are affected by temperature. Also, while most pairs of sister cells were found to be highly synchronous in each condition, the number of asynchronous pairs increased with increasing temperature, which was found to be due to disruptions in the oscillations. Finally we provide evidence that these disruptions tend to affect multiple generations as opposed to individual cells. These findings provide insight in how to design more robust synthetic circuits and in how cell division can affect their dynamics.Keywords: repressilator, robustness, synchrony, synthetic biology
Procedia PDF Downloads 4832153 Raman Tweezers Spectroscopy Study of Size Dependent Silver Nanoparticles Toxicity on Erythrocytes
Authors: Surekha Barkur, Aseefhali Bankapur, Santhosh Chidangil
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Raman Tweezers technique has become prevalent in single cell studies. This technique combines Raman spectroscopy which gives information about molecular vibrations, with optical tweezers which use a tightly focused laser beam for trapping the single cells. Thus Raman Tweezers enabled researchers analyze single cells and explore different applications. The applications of Raman Tweezers include studying blood cells, monitoring blood-related disorders, silver nanoparticle-induced stress, etc. There is increased interest in the toxic effect of nanoparticles with an increase in the various applications of nanoparticles. The interaction of these nanoparticles with the cells may vary with their size. We have studied the effect of silver nanoparticles of sizes 10nm, 40nm, and 100nm on erythrocytes using Raman Tweezers technique. Our aim was to investigate the size dependence of the nanoparticle effect on RBCs. We used 785nm laser (Starbright Diode Laser, Torsana Laser Tech, Denmark) for both trapping and Raman spectroscopic studies. 100 x oil immersion objectives with high numerical aperture (NA 1.3) is used to focus the laser beam into a sample cell. The back-scattered light is collected using the same microscope objective and focused into the spectrometer (Horiba Jobin Vyon iHR320 with 1200grooves/mm grating blazed at 750nm). Liquid nitrogen cooled CCD (Symphony CCD-1024x256-OPEN-1LS) was used for signal detection. Blood was drawn from healthy volunteers in vacutainer tubes and centrifuged to separate the blood components. 1.5 ml of silver nanoparticles was washed twice with distilled water leaving 0.1 ml silver nanoparticles in the bottom of the vial. The concentration of silver nanoparticles is 0.02mg/ml so the 0.03mg of nanoparticles will be present in the 0.1 ml nanoparticles obtained. The 25 ul of RBCs were diluted in 2 ml of PBS solution and then treated with 50 ul (0.015mg) of nanoparticles and incubated in CO2 incubator. Raman spectroscopic measurements were done after 24 hours and 48 hours of incubation. All the spectra were recorded with 10mW laser power (785nm diode laser), 60s of accumulation time and 2 accumulations. Major changes were observed in the peaks 565 cm-1, 1211 cm-1, 1224 cm-1, 1371 cm-1, 1638 cm-1. A decrease in intensity of 565 cm-1, increase in 1211 cm-1 with a reduction in 1224 cm-1, increase in intensity of 1371 cm-1 also peak disappearing at 1635 cm-1 indicates deoxygenation of hemoglobin. Nanoparticles with higher size were showing maximum spectral changes. Lesser changes observed in case of 10nm nanoparticle-treated erythrocyte spectra.Keywords: erythrocytes, nanoparticle-induced toxicity, Raman tweezers, silver nanoparticles
Procedia PDF Downloads 2932152 Tracheal Stenting to Relieve Respiratory Distress in Patient with Advanced Esophageal Malignancy and Its Anaesthetic Management
Authors: Aarti Agarwal, Ajmal Khan
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Background and Objective: Breathing difficulty is most distressing symptom for the patient and their caregivers providing palliative care to individuals with advanced malignancy. It needs to be tackled effectively and sometimes preemptively to provide relief from respiratory obstruction. Interventional procedures like tracheal stenting are becoming increasingly popular as a part of palliation for respiratory symptoms. We present a case of esophageal tumor earlier stented by Gastroenterologist to maintain esophageal patency, but the tumor outgrew to produce tracheal infiltration and thereby causing airway obstruction. Method and Result: 62-year-old man presented with unresectable Carcinoma oesophagus with inability to swallow. A metallic stent was placed by the gastroenterologist, to maintain esophageal patency and enable patient to swallow. Two months later, the patient returned to hospital in emergency with respiratory distress. CT neck and thorax revealed tumor infiltration through posterior tracheal wall. Lower extent of the tumor was till 1 cm above the carina. Airway stenting with Tracheo bronchial stent with Y configuration was planned under general anaesthesia with airway blocks. Superior Laryngeal Nerve Block, Glossopharyngeal block and Trans tracheal infiltration of local anaesthetics were performed. The patient was sedated with Fentanyl, Midazolam and propofol infusion but was breathing spontaneously. Once the rigid bronchoscope was placed inside trachea, breathing was supported with oxygen and sevoflurane. Initially, the trachea was cleared of tumor by coring. After creating space, tracheal stent was positioned and deployed. After stent placement patient was awakened, suctioned and nebulized. His respiratory stridor relieved instantaneously and was shifted to recovery. Conclusion: Airway blocks help in decreasing the incidence and severity of coughing during airway instrumentation thereby help in proper stent placement. They also reduce the requirement of general anaesthetics and hasten the post stenting recovery. Airway stent provided immediate relief to patient from symptoms of respiratory difficulty. Decision for early tracheal stenting may be taken for a select group of patients with high propensity for local spread, thereby avoiding respiratory complications and providing better quality of life in patients with inoperable malignancy.Keywords: tracheal stent, respiratory difficulty, esophageal tumor, anaesthetic management
Procedia PDF Downloads 2272151 The Importance of Fungi and Plants for a More Sustainable on Our Planet Earth
Authors: Njabe Christelle
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Fungal products are essential building blocks for change towards a more sustainable future for our planet. In nature, fungi are special in breaking down plant material by means of a rich spectrum of plant cell wall degrading enzymes. Enzymes serve as catalysts in organic synthesis. Imagine the immense benefits that the known 250000 plant genes might provide in the future through scientific investigation. Plants are the primary basis for human sustenance, used directly for food, clothing, and shelter or indirectly in processed form and through animal feeding. Fungi are the only organisms known to extensively degrade lignin, a major component of wood. Although humans cannot digest cellulose and lignin, many fungi, through their assimilation of these substances, produce food in the form of edible mushrooms.Keywords: plants, fungi, sustainable use, planet earth
Procedia PDF Downloads 812150 Mining the Proteome of Fusobacterium nucleatum for Potential Therapeutics Discovery
Authors: Abdul Musaweer Habib, Habibul Hasan Mazumder, Saiful Islam, Sohel Sikder, Omar Faruk Sikder
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The plethora of genome sequence information of bacteria in recent times has ushered in many novel strategies for antibacterial drug discovery and facilitated medical science to take up the challenge of the increasing resistance of pathogenic bacteria to current antibiotics. In this study, we adopted subtractive genomics approach to analyze the whole genome sequence of the Fusobacterium nucleatum, a human oral pathogen having association with colorectal cancer. Our study divulged 1499 proteins of Fusobacterium nucleatum, which has no homolog in human genome. These proteins were subjected to screening further by using the Database of Essential Genes (DEG) that resulted in the identification of 32 vitally important proteins for the bacterium. Subsequent analysis of the identified pivotal proteins, using the KEGG Automated Annotation Server (KAAS) resulted in sorting 3 key enzymes of F. nucleatum that may be good candidates as potential drug targets, since they are unique for the bacterium and absent in humans. In addition, we have demonstrated the 3-D structure of these three proteins. Finally, determination of ligand binding sites of the key proteins as well as screening for functional inhibitors that best fitted with the ligands sites were conducted to discover effective novel therapeutic compounds against Fusobacterium nucleatum.Keywords: colorectal cancer, drug target, Fusobacterium nucleatum, homology modeling, ligands
Procedia PDF Downloads 3882149 Comparison of the Material Response Based on Production Technologies of Metal Foams
Authors: Tamas Mankovits
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Lightweight cellular-type structures like metal foams have excellent mechanical properties, therefore the interest in these materials is widely spreading as load-bearing structural elements, e.g. as implants. Numerous technologies are available to produce metal foams. In this paper the material response of closed cell foam structures produced by direct foaming and additive technology is compared. The production technology circumstances are also investigated. Geometrical variations are developed for foam structures produced by additive manufacturing and simulated by finite element method to be able to predict the mechanical behavior.Keywords: additive manufacturing, direct foaming, finite element method, metal foam
Procedia PDF Downloads 1972148 Effect of Nicorandil in Bile Duct Ligation-Induced Liver Fibrosis in Rats: Role of Hepatic Stellate Cells
Authors: Y. S. Mohamed, L. A. Ahmed, H. A. Salem, A. M. Agha
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Liver Fibrosis is one of the most serious conditions that affect the Egyptian society. In the present study, the effect of nicorandil was investigated in experimentally-induced liver fibrosis by bile duct ligation in rats. Nicorandil (3mg/kg/day) was given orally 24 h after bile duct ligation for 14 days till the end of the experiment. Nicorandil group showed a significant improvement in liver function tests (ALT and ALP) as well as a significant decrease in oxidative stress biomarkers (TBARS and GSH), area of fibrosis and activity of hepatic stellate cells as indicated by decreased expression of alpha smooth muscle actin.Moreover, nicorandil treatment decreased HSCs proliferation due to its inhibitory effects on protein kinase C(PKC) and Platelet derived growth factor (PDGF) . Oral administration of either glibenclamide (10 mg/kg/day)(a KATP channel blocker) or L-NAME (30 mg/kg/day) (an inhibitor of nitric oxide synthase) blocked the protective effects of nicorandil. However, nicorandil and L-NAME treated group showed more or less results similar to that of untreated bile duct ligated group. In conclusion, nicorandil was effective against the development of bile duct ligated-induced liver fibrosis in rats where activation of the NO pathway plays an important role in the protective effect nicorandil.Keywords: hepatic stellate cells, nicorandil, nitric oxide donor, liver fibrosis
Procedia PDF Downloads 6112147 Ab Initio Study of Hexahalometallate Single Crystals K₂XBr₆ (X=Se, Pt)
Authors: M. Fatmi, B. Gueridi, Z. Zerrougui
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Some physical properties of hexahalometallate K₂XBr₆(X=Se, Pt) were computed in the zinc blend structure using generalized gradient approximation. The cell constant of K₂SeBr₆ and K₂PtBr₆ is consistent with the experiment value quoted in the literature, where the error is 0.95 % and 1 %. K₂SeBr₆ and K₂PtBr₆ present covalent bonding, high anisotropy and are ductile. The elastic constants of K₂SeBr₆ and K₂PtBr₆ are significantly smaller due to their larger reticular distances and lower Colombian forces, and then they are soft and damage tolerant. The interatomic separation is greater in K₂SeBr₆ than in K₂PtBr₆; hence the Colombian interaction in K₂PtBr₆ is greater than that of K2SeBr₆. The internal coordinate of the Br atom in K₂PtBr₆ is lower than that of the same atom in K2SeBr₆, and this can be explained by the fact that it is inversely proportional to the atom radius of Se and Pt. There are two major plasmonic processes, with intensities of 3.7 and 1.35, located around 53.5 nm and 72.8 nm for K₂SeBr₆ and K₂PtBr₆.Keywords: hexahalometallate, band structure, morphology, absorption, band gap, absorber
Procedia PDF Downloads 932146 Synthesis and Biological Evaluation of Pyridine Derivatives as Antimicrobial Agents
Authors: Dagim Ali Hussen, Adnan A. Bekhit, Ariaya Hymete
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In this study, several pyridine derivatives were synthesized and evaluated for their in vitro antimicrobial activity against gram-positive bacteria (S. aureus and B. Cereus), gram-negative bacteria (P. aeruginosa and E. coli) and fungus (C. albican and A niger). The intermediate chalcone derivative 2a,b was synthesized by condensation of pyrazole aldehydes 1a,b with acetophenone in alcoholic KOH. Cyclization of 2a,b with ethyl cyanoacetate ad ammonium acetate resulted in pyridine carbonitrile derivatives 3a,b. Furthermore, condensation of pyridine-4-carboxaldeyhe with different amino-derivatives gave rise to pyridine derivatives 5a,b, 6a,b. The oxadiazole derivative 7a was prepared by cyclization of 6a with acetic anhydride. Characterization of the synthesized compound was performed using IR, 1H NMR, 13C NMR spectra and elemental microanalyses. The antimicrobial results revealed that compounds 5a, 6b and 7a exhibited half fold antibacterial activity compared to ampicillin, against B. cereus. On the other hand, compound 3b showed an equivalent activity compared to miconazole against candida albican (CANDAL 03) and to clotrimazole against the clinical isolate candida albican 6647. Moreover, this compound 3b was further tested for its acute toxicity profile. The results showed that oral LD50 is more that 300 mg/kg and parentral LD50 is more than 100 mg/kg. Compound 3b is a good candidate for antifungal agent with good toxicity profile, and deserves more chemical derivatization and clinical study.Keywords: antifungal, antimicrobial, Candida albican, pyridine
Procedia PDF Downloads 4982145 Ternary Content Addressable Memory Cell with a Leakage Reduction Technique
Authors: Gagnesh Kumar, Nitin Gupta
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Ternary Content Addressable Memory cells are mainly popular in network routers for packet forwarding and packet classification, but they are also useful in a variety of other applications that require high-speed table look-up. The main TCAM-design challenge is to decrease the power consumption associated with the large amount of parallel active circuitry, without compromising with speed or memory density. Furthermore, when the channel length decreases, leakage power becomes more significant, and it can even dominate dynamic power at lower technologies. In this paper, we propose a TCAM-design technique, called Virtual Power Supply technique that reduces the leakage by a substantial amount.Keywords: match line (ML), search line (SL), ternary content addressable memory (TCAM), Leakage power (LP)
Procedia PDF Downloads 2992144 Adequate Nutritional Support and Monitoring in Post-Traumatic High Output Duodenal Fistula
Authors: Richa Jaiswal, Vidisha Sharma, Amulya Rattan, Sushma Sagar, Subodh Kumar, Amit Gupta, Biplab Mishra, Maneesh Singhal
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Background: Adequate nutritional support and daily patient monitoring have an independent therapeutic role in the successful management of high output fistulae and early recovery after abdominal trauma. Case presentation: An 18-year-old girl was brought to AIIMS emergency with alleged history of fall of a heavy weight (electric motor) over abdomen. She was evaluated as per Advanced Trauma Life Support(ATLS) protocols and diagnosed to have significant abdominal trauma. After stabilization, she was referred to Trauma center. Abdomen was guarded and focused assessment with sonography for trauma(FAST) was found positive. Complete duodenojejunal(DJ) junction transection was found at laparotomy, and end-to-end repair was done. However, patient was re-explored in view of biliary peritonitis on post-operative day3, and anastomotic leak was found with sloughing of duodenal end. Resection of non-viable segments was done followed by side-to-side anastomosis. Unfortunately, the anastomosis leaked again, this time due to a post-anastomotic kink, diagnosed on dye study. Due to hostile abdomen, the patient was planned for supportive care, with plan of build-up and delayed definitive surgery. Percutaneous transheptic biliary drainage (PTBD) and STSG were required in the course as well. Nutrition: In intensive care unit (ICU), major goals of nutritional therapy were to improve wound healing, optimize nutrition, minimize enteral feed associated complications, reduce biliary fistula output, and prepare the patient for definitive surgeries. Feeding jejunostomy (FJ) was started from day 4 at the rate of 30ml/h along with total parenteral nutrition (TPN) and intra-venous (IV) micronutrients support. Due to high bile output, bile refeed started from day 13.After 23 days of ICU stay, patient was transferred to general ward with body mass index (BMI)<11kg/m2 and serum albumin –1.5gm%. Patient was received in the ward in catabolic phase with high risk of refeeding syndrome. Patient was kept on FJ bolus feed at the rate of 30–50 ml/h. After 3–4 days, while maintaining patient diet book log it was observed that patient use to refuse feed at night and started becoming less responsive with every passing day. After few minutes of conversation with the patient for a couple of days, she complained about enteral feed discharge in urine, mild pain and sign of dumping syndrome. Dye study was done, which ruled out any enterovesical fistula and conservative management were planned. At this time, decision was taken for continuous slow rate feeding through commercial feeding pump at the rate of 2–3ml/min. Drastic improvement was observed from the second day in gastro-intestinal symptoms and general condition of the patient. Nutritional composition of feed, TPN and diet ranged between 800 and 2100 kcal and 50–95 g protein. After STSG, TPN was stopped. Periodic diet counselling was given to improve oral intake. At the time of discharge, serum albumin level was 2.1g%, weight – 38.6, BMI – 15.19 kg/m2. Patient got discharge on an oral diet. Conclusion: Successful management of post-traumatic proximal high output fistulae is a challenging task, due to impaired nutrient absorption and enteral feed associated complications. Strategic- and goal-based nutrition support can salvage such critically ill patients, as demonstrated in the present case.Keywords: nutritional monitoring, nutritional support, duodenal fistula, abdominal trauma
Procedia PDF Downloads 2612143 Comparison of the Toxicity of Silver and Gold Nanoparticles in Murine Fibroblasts
Authors: Šárka Hradilová, Aleš Panáček, Radek Zbořil
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Nanotechnologies are considered the most promising fields with high added value, brings new possibilities in various sectors from industry to medicine. With the growing of interest in nanomaterials and their applications, increasing nanoparticle production leads to increased exposure of people and environment with ‘human made’ nanoparticles. Nanoparticles (NPs) are clusters of atoms in the size range of 1–100 nm. Metal nanoparticles represent one of the most important and frequently used types of NPs due to their unique physical, chemical and biological properties, which significantly differ from those of bulk material. Biological properties including toxicity of metal nanoparticles are generally determined by their size, size distribution, shape, surface area, surface charge, surface chemistry, stability in the environment and ability to release metal ions. Therefore, the biological behavior of NPs and their possible adverse effect cannot be derived from the bulk form of material because nanoparticles show unique properties and interactions with biological systems just due to their nanodimensions. Silver and gold NPs are intensively studied and used. Both can be used for instance in surface enhanced Raman spectroscopy, a considerable number of applications of silver NPs is associated with antibacterial effects, while gold NPs are associated with cancer treatment and bio imaging. Antibacterial effects of silver ions are known for centuries. Silver ions and silver-based compounds are highly toxic to microorganisms. Toxic properties of silver NPs are intensively studied, but the mechanism of cytoxicity is not fully understood. While silver NPs are considered toxic, gold NPs are referred to as toxic but also innocuous for eukaryotic cells. Therefore, gold NPs are used in various biological applications without a risk of cell damaging, even when we want to suppress the growth of cancer cells. Thus, gold NPs are toxic or harmless. Because most studies comparing particles of various sizes prepared in various ways, and testing is performed on different cell lines, it is very difficult to generalize. The novelty and significance of our research is focused to the complex biological effects of silver and gold NPs prepared by the same method, have the same parameters and the same stabilizer. That is why we can compare the biological effects of pure nanometals themselves based on their chemical nature without the influence of other variable. Aim of our study therefore is to compare the cytotoxic effect of two types of noble metal NPs focusing on the mechanisms that contribute to cytotoxicity. The study was conducted on murine fibroblasts by selected common used tests. Each of these tests monitors the selected area related to toxicity and together provides a comprehensive view on the issue of interactions of nanoparticles and living cells.Keywords: cytotoxicity, gold nanoparticles, mechanism of cytotoxicity, silver nanoparticles
Procedia PDF Downloads 2542142 Prediction of Time to Crack Reinforced Concrete by Chloride Induced Corrosion
Authors: Anuruddha Jayasuriya, Thanakorn Pheeraphan
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In this paper, a review of different mathematical models which can be used as prediction tools to assess the time to crack reinforced concrete (RC) due to corrosion is investigated. This investigation leads to an experimental study to validate a selected prediction model. Most of these mathematical models depend upon the mechanical behaviors, chemical behaviors, electrochemical behaviors or geometric aspects of the RC members during a corrosion process. The experimental program is designed to verify the accuracy of a well-selected mathematical model from a rigorous literature study. Fundamentally, the experimental program exemplifies both one-dimensional chloride diffusion using RC squared slab elements of 500 mm by 500 mm and two-dimensional chloride diffusion using RC squared column elements of 225 mm by 225 mm by 500 mm. Each set consists of three water-to-cement ratios (w/c); 0.4, 0.5, 0.6 and two cover depths; 25 mm and 50 mm. 12 mm bars are used for column elements and 16 mm bars are used for slab elements. All the samples are subjected to accelerated chloride corrosion in a chloride bath of 5% (w/w) sodium chloride (NaCl) solution. Based on a pre-screening of different models, it is clear that the well-selected mathematical model had included mechanical properties, chemical and electrochemical properties, nature of corrosion whether it is accelerated or natural, and the amount of porous area that rust products can accommodate before exerting expansive pressure on the surrounding concrete. The experimental results have shown that the selected model for both one-dimensional and two-dimensional chloride diffusion had ±20% and ±10% respective accuracies compared to the experimental output. The half-cell potential readings are also used to see the corrosion probability, and experimental results have shown that the mass loss is proportional to the negative half-cell potential readings that are obtained. Additionally, a statistical analysis is carried out in order to determine the most influential factor that affects the time to corrode the reinforcement in the concrete due to chloride diffusion. The factors considered for this analysis are w/c, bar diameter, and cover depth. The analysis is accomplished by using Minitab statistical software, and it showed that cover depth is the significant effect on the time to crack the concrete from chloride induced corrosion than other factors considered. Thus, the time predictions can be illustrated through the selected mathematical model as it covers a wide range of factors affecting the corrosion process, and it can be used to predetermine the durability concern of RC structures that are vulnerable to chloride exposure. And eventually, it is further concluded that cover thickness plays a vital role in durability in terms of chloride diffusion.Keywords: accelerated corrosion, chloride diffusion, corrosion cracks, passivation layer, reinforcement corrosion
Procedia PDF Downloads 2182141 Neuron-Based Control Mechanisms for a Robotic Arm and Hand
Authors: Nishant Singh, Christian Huyck, Vaibhav Gandhi, Alexander Jones
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A robotic arm and hand controlled by simulated neurons is presented. The robot makes use of a biological neuron simulator using a point neural model. The neurons and synapses are organised to create a finite state automaton including neural inputs from sensors, and outputs to effectors. The robot performs a simple pick-and-place task. This work is a proof of concept study for a longer term approach. It is hoped that further work will lead to more effective and flexible robots. As another benefit, it is hoped that further work will also lead to a better understanding of human and other animal neural processing, particularly for physical motion. This is a multidisciplinary approach combining cognitive neuroscience, robotics, and psychology.Keywords: cell assembly, force sensitive resistor, robot, spiking neuron
Procedia PDF Downloads 3492140 Performance Analysis of IDMA Scheme Using Quasi-Cyclic Low Density Parity Check Codes
Authors: Anurag Saxena, Alkesh Agrawal, Dinesh Kumar
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The next generation mobile communication systems i.e. fourth generation (4G) was developed to accommodate the quality of service and required data rate. This project focuses on multiple access technique proposed in 4G communication systems. It is attempted to demonstrate the IDMA (Interleave Division Multiple Access) technology. The basic principle of IDMA is that interleaver is different for each user whereas CDMA employs different signatures. IDMA inherits many advantages of CDMA such as robust against fading, easy cell planning; dynamic channel sharing and IDMA increase the spectral efficiency and reduce the receiver complexity. In this, performance of IDMA is analyzed using QC-LDPC coding scheme further it is compared with LDPC coding and at last BER is calculated and plotted in MATLAB.Keywords: 4G, QC-LDPC, CDMA, IDMA
Procedia PDF Downloads 3232139 Key Drivers Motivating Prospective International Students to Study Abroad and Their Attitude to University Rankings
Authors: Dasha Karzunina, Laura Bridgestock
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Our oral presentation will be based on our qualitative and quantitative findings into motivations and challenges faced by international and UK students when choosing a university abroad. The insight was gathered through a series of over 60 focus groups held with prospective university students all over the world, including masters and PhD applicants. We spoke to students face-to-face in Latin America, North American, India, China, South East Asia and the major European cities. A survey was carried out alongside, to gather additional insight on their priorities and attitudes to universities’ reputation, collecting over 1,800 responses. The session’s aims are to break down some of the myths about the perspectives of international students and inform university leaders interested in recruiting more highly talented students from abroad and those currently working with international students. As a provider of one of the most demanded resources in higher education, QS World University Rankings, we specialize in understanding universities’ performance, their institutional brand and the impact of rankings on student recruitment. We therefore feel we are well placed to carry out and present this research. We hope for our findings to act as a bridge between bright students and their future universities abroad. We intend for our session to be interactive and so are happy to go into more depth on any of the destinations we visited, depending on what the audience is most interested in and which questions we receive.Keywords: international student recruitment, market research, rankings, study abroad
Procedia PDF Downloads 2362138 Movement of Metallic Inclusions in the Volume of Synthetic Diamonds at High Pressure and High Temperature in the Temperature Gradient Field
Authors: P. I. Yachevskaya, S. A. Terentiev, M. S. Kuznetsov
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Several synthetic HPHT diamonds with metal inclusions have been studied. To have possibility of investigate the movement and transformation of the inclusions in the volume of the diamond the samples parallele-piped like shape has been made out of diamond crystals. The calculated value of temperature gradient in the samples of diamond which was placed in high-pressure cell was about 5-10 grad/mm. Duration of the experiments was in range 2-16 hours. All samples were treated several times. It has been found that the volume (dimensions) of inclusions, temperature, temperature gradient and the crystallographic orientation of the samples in the temperature field affects the movement speed of inclusions. Maximum speed of inclusions’ movement reached a value 150 µm/h.Keywords: diamond, inclusions, temperature gradient, HPHT
Procedia PDF Downloads 5102137 The Importance of an Intensive Course in English for University Entrants: Teachers’ and Students’ Experience and Perception
Authors: Ruwan Gunawardane
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This paper attempts to emphasize the benefits of conducting an intensive course in English for university entrants. In the Sri Lankan university context, an intensive course in English is usually conducted amidst various obstacles. In the 1970s and 1980s, undergraduates had intensive programmes in English for two to three months. Towards the end of the 1990s, a programme called General English Language Training (GELT) was conducted for the new students, and it was done outside universities before they entered their respective universities. Later it was not conducted, and that also resulted in students’ poor performance in English at university. However, having understood its importance, an eight week long intensive course in English was conducted for the new intake of the Faculty of Science, University of Ruhuna. As the findings show, the students heavily benefited from the programme. More importantly, they had the opportunity to refresh their knowledge of English gained at school and private institutions while gaining new knowledge. Another advantage was that they had plenty of time to enjoy learning English since the learners had adequate opportunities to carry out communicative tasks and the course was not exam-oriented, which reduced their fear of making mistakes in English considerably. The data was collected through an open-ended questionnaire given to 60 students, and their oral feedback was also taken into consideration. In addition, a focus group interview with 6 teachers was also conducted to get an idea about their experience and perception. The data were qualitatively analyzed. The findings suggest that an intensive programme in English undoubtedly lays a good foundation for the students’ academic career at university.Keywords: intensive course, English, teachers, undergraduates, experience, perception
Procedia PDF Downloads 1332136 Negotiating Story Telling: Rhetoric and Reality of Rural Marginalization in the Era of Visual Culture
Authors: Vishnu Satya
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Rural communities form the backbone of our society. These communities are self-contained, for the most part, in how they can sustain themselves. Except for the essentials, they are primarily dependent on the state for their development and prosperity. The state claims to provide these through policies and agencies which are designed to guide their livelihood and future. It is assumed that the state-run policies are effective and are reaching the intended audience. Though in reality, there is an ever-widening gap between the two. The interviews conducted with farmers suggests that the support provided by the state to this marginalized community falls far short of their expectations, leaving them helpless. This paper discusses the methods used in bringing the status quo of the marginalized farmers to the forefront by comparing-and-contrasting the existing rhetoric and reality of the rural diaspora. It is seen from the hands-on oral accounts of farmers that they are left hanging between the state and their farms. Unrepresented, this community's progress and future stand severely affected. The paper presents how the visual medium acts as a catalyst for social advocacy by bridging the gap between administrative services and the marginalized rural communities. The finding was that there exists a disconnect between policymakers and the farming community, which has hindered the progress of the farmers. These two communities live exclusively from each other. In conclusion, it is seen that when the gaps between administrators and farmers are plugged through grass-root efforts utilizing visual medium, the farmer's economic situation got better, and the community prospered.Keywords: farmers, social advocacy, marginalized, story telling
Procedia PDF Downloads 1532135 Reconstruction of Alveolar Bone Defects Using Bone Morphogenetic Protein 2 Mediated Rabbit Dental Pulp Stem Cells Seeded on Nano-Hydroxyapatite/Collagen/Poly(L-Lactide)
Authors: Ling-Ling E., Hong-Chen Liu, Dong-Sheng Wang, Fang Su, Xia Wu, Zhan-Ping Shi, Yan Lv, Jia-Zhu Wang
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Objective: The objective of the present study is to evaluate the capacity of a tissue-engineered bone complex of recombinant human bone morphogenetic protein 2 (rhBMP-2) mediated dental pulp stem cells (DPSCs) and nano-hydroxyapatite/collagen/poly(L-lactide)(nHAC/PLA) to reconstruct critical-size alveolar bone defects in New Zealand rabbit. Methods: Autologous DPSCs were isolated from rabbit dental pulp tissue and expanded ex vivo to enrich DPSCs numbers, and then their attachment and differentiation capability were evaluated when cultured on the culture plate or nHAC/PLA. The alveolar bone defects were treated with nHAC/PLA, nHAC/PLA+rhBMP-2, nHAC/PLA+DPSCs, nHAC/PLA+DPSCs+rhBMP-2, and autogenous bone (AB) obtained from iliac bone or were left untreated as a control. X-ray and a polychrome sequential fluorescent labeling were performed post-operatively and the animals were sacrificed 12 weeks after operation for histological observation and histomorphometric analysis. Results: Our results showed that DPSCs expressed STRO-1 and vementin, and favoured osteogenesis and adipogenesis in conditioned media. DPSCs attached and spread well, and retained their osteogenic phenotypes on nHAC/PLA. The rhBMP-2 could significantly increase protein content, alkaline phosphatase (ALP) activity/protein, osteocalcin (OCN) content, and mineral formation of DPSCs cultured on nHAC/PLA. The X-ray graph, the fluorescent, histological observation and histomorphometric analysis showed that the nHAC/PLA+DPSCs+rhBMP-2 tissue-engineered bone complex had an earlier mineralization and more bone formation inside the scaffold than nHAC/PLA, nHAC/PLA+rhBMP-2 and nHAC/PLA+DPSCs, or even autologous bone. Implanted DPSCs contribution to new bone were detected through transfected eGFP genes. Conclutions: Our findings indicated that stem cells existed in adult rabbit dental pulp tissue. The rhBMP-2 promoted osteogenic capability of DPSCs as a potential cell source for periodontal bone regeneration. The nHAC/PLA could serve as a good scaffold for autologous DPSCs seeding, proliferation and differentiation. The tissue-engineered bone complex with nHAC/PLA, rhBMP-2, and autologous DPSCs might be a better alternative to autologous bone for the clinical reconstruction of periodontal bone defects.Keywords: nano-hydroxyapatite/collagen/poly (L-lactide), dental pulp stem cell, recombinant human bone morphogenetic protein, bone tissue engineering, alveolar bone
Procedia PDF Downloads 4012134 Haematological Alterations in Anaemic Bali Cattle Raised in Semi-Intensive System
Authors: Jully Handoko
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Screening for anaemia in Bali cattle of Bangkinang Seberang subdistrict, kampar regency, Riau, Indonesia, had been conducted. The aim of the study was to analyse hematological alterations in the anaemic Bali cattle. A number of 75 Bali cattle were screened for anaemia on the basis of Haemoglobin (Hb) concentration. The other haematological parameters that were measured including packed cell volume (PCV), total erythrocyte count (TEC), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC). The screening showed that 18 (24.00%) of Bali cattle were anaemic. Haematological values of Hb, PCV, TEC, MCV, MCH, and MCHC were significantly (p<0.05) lower in anaemic Bali cattle compared to non-anaemic Bali cattle.Keywords: anaemia, Bali cattle, alteration, semi-intensive system
Procedia PDF Downloads 5032133 Problems and Solutions in the Application of ICP-MS for Analysis of Trace Elements in Various Samples
Authors: Béla Kovács, Éva Bódi, Farzaneh Garousi, Szilvia Várallyay, Áron Soós, Xénia Vágó, Dávid Andrási
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In agriculture for analysis of elements in different food and food raw materials, moreover environmental samples generally flame atomic absorption spectrometers (FAAS), graphite furnace atomic absorption spectrometers (GF-AAS), inductively coupled plasma optical emission spectrometers (ICP-OES) and inductively coupled plasma mass spectrometers (ICP-MS) are routinely applied. An inductively coupled plasma mass spectrometer (ICP-MS) is capable for analysis of 70-80 elements in multielemental mode, from 1-5 cm3 volume of a sample, moreover the detection limits of elements are in µg/kg-ng/kg (ppb-ppt) concentration range. All the analytical instruments have different physical and chemical interfering effects analysing the above types of samples. The smaller the concentration of an analyte and the larger the concentration of the matrix the larger the interfering effects. Nowadays there is very important to analyse growingly smaller concentrations of elements. From the above analytical instruments generally the inductively coupled plasma mass spectrometer is capable of analysing the smallest concentration of elements. The applied ICP-MS instrument has Collision Cell Technology (CCT) also. Using CCT mode certain elements have better (smaller) detection limits with 1-3 magnitudes comparing to a normal ICP-MS analytical method. The CCT mode has better detection limits mainly for analysis of selenium, arsenic, germanium, vanadium and chromium. To elaborate an analytical method for trace elements with an inductively coupled plasma mass spectrometer the most important interfering effects (problems) were evaluated: 1) Physical interferences; 2) Spectral interferences (elemental and molecular isobaric); 3) Effect of easily ionisable elements; 4) Memory interferences. Analysing food and food raw materials, moreover environmental samples an other (new) interfering effect emerged in ICP-MS, namely the effect of various matrixes having different evaporation and nebulization effectiveness, moreover having different quantity of carbon content of food and food raw materials, moreover environmental samples. In our research work the effect of different water-soluble compounds furthermore the effect of various quantity of carbon content (as sample matrix) were examined on changes of intensity of the applied elements. So finally we could find “opportunities” to decrease or eliminate the error of the analyses of applied elements (Cr, Co, Ni, Cu, Zn, Ge, As, Se, Mo, Cd, Sn, Sb, Te, Hg, Pb, Bi). To analyse these elements in the above samples, the most appropriate inductively coupled plasma mass spectrometer is a quadrupole instrument applying a collision cell technique (CCT). The extent of interfering effect of carbon content depends on the type of compounds. The carbon content significantly affects the measured concentration (intensities) of the above elements, which can be corrected using different internal standards.Keywords: elements, environmental and food samples, ICP-MS, interference effects
Procedia PDF Downloads 5042132 A Quality Improvement Project to Assess the Impact of Orthognathic Surgery on the Quality of Life of Patients: Pre-Operatively versus Post-Operatively
Authors: Fiona Lourenco, William Allen
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Dentofacial deformities are primarily surgically treated via orthognathic surgery. Health-related quality of life is concerned with aspects of quality of life that relate specifically to an individual’s health. Design and Setting: Retrospective analysis of patients who had orthognathic surgery from January 2018 - December 2022 at the trust using the previously validated Orthognathic Quality of Life questionnaire (OQoL). Materials and Methods: 32 Patient questionnaires (which included pre-operative and post-operative separate sections) were obtained via telephone survey. The data was analysed using the two-tailed paired t-test and Wilcoxon signed-rank test. Results: The change in perception post-surgery was highly significant (both tests resulted in p<0.001 for overall analysis as well as for each domain). Overall, a 74% improvement in QoL was seen following orthognathic surgery. Reports of improvement in each domain were as follows: 71% in the social aspect of the deformity domain, 76% in facial aesthetics, 60% in function, and 57% improvement in awareness of facial deformity. Conclusion: The assessment of QoL is becoming progressively imperative in clinical research. The above data shows that orthognathic surgery has a significant improvement in the QoL of patients post-operatively. The results demonstrate improvement in all domains, with perceptions in facial aesthetics seeing the highest change post-operatively.Keywords: dentofacial, oral, facial asymmetry, orthognathic surgery, quality of life
Procedia PDF Downloads 802131 Glycyrrhizic Acid Inhibits Lipopolysaccharide-Stimulated Bovine Fibroblast-Like Synoviocyte, Invasion through Suppression of TLR4/NF-κB-Mediated Matrix Metalloproteinase-9 Expression
Authors: Hosein Maghsoudi
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Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9
Procedia PDF Downloads 3912130 Effect of Arbutus Pavarii ( Shemari ) Libyan Medical Plant on Ethylene Glycol Induced Urolithiasis in Male Albino Rats
Authors: Khaled. M.Benelhaj, Moada Elbadary
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The present investigation is carried out to evaluate the effect of aqueous extract of Arbutus Pavarii (Shemari) Libyan medical plant on ethylene glycol(EG) induce lithiasis in adult male albino rats. The lithiasis was induced to rats by oral administration of EG (0.75 w/v%) for 21 days(group 1). Aqueous extract of Shemari (200 mg/kg) was given orally from 1st day for preventive regimen (group 2) and from day 21st up to 42nd day for curative regimen (group 3). The results indicated that the EG elevated the urinary ionic of calcium, oxalates and inorganic phosphate. The Shemari significantly (P<0.01) reduced the levels of these ions. The histopathological findings showed that EG caused marked pathological changes in renal cortex; necrosis of glomerular tufts; mildy thickened bowman’s capsule and coagulative necrosis of large number of convoluted tubules. However, the histological changes in preventive regimen group 2 showed the same changes observed in group 1, but milder in severity and less in frequency. It conclude that Shemari do reduce the urinary ionic levels of calcium, oxalates and inorganic phosphate but failed to prevent complete deterioration effects of EG on kidney structures.Keywords: EG, shamari, kidney stone, Libyan medical plant, glycol, oxalates
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