Search results for: immune checkpoint inhibitors
399 Administration of Lactobacillus plantarum PS128 Improves Animal Behavior and Monoamine Neurotransmission in Germ-Free Mice
Authors: Liu Wei-Hsien, Chuang Hsiao-Li, Huang Yen-Te, Wu Chien-Chen, Chou Geng-Ting, Tsai Ying-Chieh
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Intestinal microflora play an important role in communication along the gut-brain axis. Probiotics, defined as live bacteria or bacterial products, confer a significant health benefit to the host. Here we administered Lactobacillus plantarum PS128 (PS128) to the germ-free (GF) mouse to investigate the impact of the gut-brain axis on emotional behavior. Administration of live PS128 significantly increased the total distance traveled in the open field test; it decreased the time spent in the closed arm and increased the time spent and total entries into the open arm in the elevated plus maze. In contrast, heat-killed PS128 caused no significant changes in the GF mice. Treatment with live PS128 significantly increased levels of both serotonin and dopamine in the striatum, but not in the prefrontal cortex or hippocampus. However, live PS128 did not alter pro- or anti-inflammatory cytokine production by mitogen-stimulated splenocytes. The above data indicate that the normalization of emotional behavior correlated with monoamine neurotransmission, but not with immune activity. Our findings suggest that daily intake of the probiotic PS128 could ameliorate neuropsychiatric disorders such as anxiety and excessive psychological stress.Keywords: dopamine, hypothalamic-pituitary-adrenal axis, intestinal microflora, serotonin
Procedia PDF Downloads 413398 Design and in Slico Study of the Truncated Spike-M-N SARS-CoV-2 as a Novel Effective Vaccine Candidate
Authors: Aghasadeghi MR., Bahramali G., Sadat SM., Sadeghi SA., Yousefi M., Khodaei K., Ghorbani M., Sadat Larijani M.
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Background:The emerging COVID-19 pandemic is a serious concernfor the public health worldwide. Despite the many mutations in the virus genome, it is important to find an effective vaccine against viral mutations. Therefore, in current study, we aimed at immunoinformatic evaluation of the virus proteins immunogenicity to design a preventive vaccine candidate, which could elicit humoral and cellular immune responses as well. Methods:Three antigenic regions are included;Spike, Membrane, and Nucleocapsid amino acid sequences were obtained, and possible fusion proteins were assessed andcompared by immunogenicity, structural features, and population coverage. The best fusion protein was also evaluated for MHC-I and MHC-II T-cell epitopes and the linear and conformational B-cell epitopes. Results: Among the four predicted models, the truncated Spike protein in fusion with M and N proteins is composed of 24 highly immunogenic human MHC class I and 29 MHC class II, along with 14 B-cell linear and 61 discontinues epitopes. Also, the selected protein has high antigenicity and acceptable population coverage of 82.95% in Iran and 92.51% in Europe. Conclusion: The data indicate that the truncated Spike-M-N SARS-CoV-2form which could be potential targets of neutralizing antibodies. The protein also has the ability to stimulate humoral and cellular immunity. The in silico study provided the fusion protein as a potential preventive vaccine candidate for further in vivo evaluation.Keywords: SARS-CoV-2, immunoinformatic, protein, vaccine
Procedia PDF Downloads 222397 Analyzing the Impact of Migration on HIV and AIDS Incidence Cases in Malaysia
Authors: Ofosuhene O. Apenteng, Noor Azina Ismail
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The human immunodeficiency virus (HIV) that causes acquired immune deficiency syndrome (AIDS) remains a global cause of morbidity and mortality. It has caused panic since its emergence. Relationships between migration and HIV/AIDS have become complex. In the absence of prospectively designed studies, dynamic mathematical models that take into account the migration movement which will give very useful information. We have explored the utility of mathematical models in understanding transmission dynamics of HIV and AIDS and in assessing the magnitude of how migration has impact on the disease. The model was calibrated to HIV and AIDS incidence data from Malaysia Ministry of Health from the period of 1986 to 2011 using Bayesian analysis with combination of Markov chain Monte Carlo method (MCMC) approach to estimate the model parameters. From the estimated parameters, the estimated basic reproduction number was 22.5812. The rate at which the susceptible individual moved to HIV compartment has the highest sensitivity value which is more significant as compared to the remaining parameters. Thus, the disease becomes unstable. This is a big concern and not good indicator from the public health point of view since the aim is to stabilize the epidemic at the disease-free equilibrium. However, these results suggest that the government as a policy maker should make further efforts to curb illegal activities performed by migrants. It is shown that our models reflect considerably the dynamic behavior of the HIV/AIDS epidemic in Malaysia and eventually could be used strategically for other countries.Keywords: epidemic model, reproduction number, HIV, MCMC, parameter estimation
Procedia PDF Downloads 366396 Anaerobic Fermentation Process for Production of Biohydrogen from Pretreated Fruit Wastes
Authors: A. K. R. Gobinath, He Jianzhong, Kun-Lin Yang
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Fruit waste was used as a feedstock to produce biohydrogen in this study. Fruit waste used in this study was collected from several fruit juice stalls in Singapore. Based on our observation, the fruit waste contained 35-40% orange, 10-20% watermelon, 10-15% apple, 10-15% pineapple, 1-5% mango. They were mixed with water (1:1 ratio based on wet biomass) and blended to attain homogenous mixtures. Later, fruit waste was subjected to one of the following pretreatments: autoclave (121 °C for 20min), microwave (20min) or both. After pretreatment, the total sugar concentration in the hydrolysate was high (>12g/l) when both autoclave and microwave were applied. In contrast, samples without pretreatment measured only less than 2g/l of sugar. While using these hydrolysates as carbon sources, Clostridium strain BOH3 produces 2526-3126 ml/l of hydrogen after 72h of anaerobic fermentation. The hydrogen yield was 295-300 ml/g of sugar which is close to the hydrogen yields from glucose (338 ml/gm) and xylose (330 ml/gm). Our HPLC analysis showed that fruit waste hydrolysate contained oligosugars (25-27%), sucrose (18-23%), fructose (25-30%), glucose (10-15%) and mannose (2-5%). Additionally, pretreatment led to the release of free amino acids (160-512 mg/l), calcium (7.8-12.9 ppm), magnesium (4.32-6.55 ppm), potassium (5.4-65.1 ppm) and sodium (0.4-0.5 ppm) into the hydrolysate. These nutrients were able to support strain-BOH3 to grow and produce high level of hydrogen. Notably, unlike other pretreatment methods (with strong acids and bases), these pretreatment techniques did not generate any inhibitors (e.g. furfural and phenolic acids) to suppress the hydrogen production. Interestingly, strain BOH3 can also ferment pretreated fruit waste slurry and produce hydrogen with a high yield (156-343 ml/gm fruit waste). While fermenting pretreated fruit waste slurry, strain-BOH3 excreted several saccharolytic enzymes majorly xylanase (1.84U/ml), amylase (1.10U/ml), pectinase (0.36U/ml) and cellulase (0.43U/ml). Due to expressions of these enzymes, strain BOH3 was able to directly utilize pretreated fruit waste hydrolysate and produces high-level of hydrogen.Keywords: autoclave pretreatment, biohydrogen production, clostridial fermentation, fruit waste, and microwave pretreatment
Procedia PDF Downloads 532395 Combinational Therapeutic Targeting of BRD4 and CDK7 Synergistically Induces Anticancer Effects in Hepatocellular Carcinoma
Authors: Xinxiu Li, Chuqian Zheng, Yanyan Qian, Hong Fan
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Objectives: In hepatocellular carcinoma (HCC), oncogenes are continuously and robustly transcribed due to aberrant expression of essential components of the trans-acting super-enhancers (SE) complex. Preclinical and clinical trials are now being conducted on small-molecule inhibitors that target core-transcriptional components, including as transcriptional bromodomain protein 4 (BRD4) and cyclin-dependent kinase 7 (CDK7), in a number of malignant tumors. This study aims to explore whether co-overexpression of BRD4 and CDK7 is a potential marker of worse prognosis and a combined therapeutic target in HCC. Methods: The expression pattern of BRD4 and CDK7 and their correlation with prognosis in HCC were analyzed by RNA sequencing data and survival data of HCC patients from TCGA and GEO datasets. The protein levels of BRD4 and CDK7 were determined by immunohistochemistry (IHC), and survival data of patients were analyzed using the Kaplan-Meier method. The mRNA expression levels of genes in HCC cell lines were evaluated by quantitative PCR (q-PCR). CCK-8 and colony formation assays were conducted to assess cell proliferation of HCC upon treatment with BRD4 inhibitor JQ1 or/and CDK7 inhibitor THZ1. Results: It was shown that BRD4 and CDK7 were often overexpressed in HCCs and were associated with poor prognosis of HCC by analyzing the TCGA and GEO datasets. BRD4 or CDK7 overexpression was related to a lower survival rate. It's interesting to note that co-overexpression of CDK7 and BRD4 was a worse prognostic factor in HCC. Treatment with JQ1 or THZ1 alone had an inhibitory effect on cell proliferation; however, when JQ1 and THZ1 were combined, there was a more notable suppression of cell growth. At the same time, the combined use of JQ1 and THZ1 synergistically suppresses the expression of HCC driver genes. Conclusion: Our research revealed that BRD4 and CDK7 coupled can be a useful biomarker in HCC prognosis and the combination of JQ1 and THZ1 can be a promising therapeutic therapy against HCC.Keywords: BRD4, CDK7, cell proliferation, combined inhibition
Procedia PDF Downloads 53394 Treatment of Type 2 Diabetes Mellitus: Physicians’ Adherence to the American Diabetes Association Guideline in Central Region, Saudi Arabia
Authors: Ibrahim Mohammed
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Background: Diabetes mellitus is a chronic disease that can cause devastating secondary complications, reducing the quality and length of life as well as increasing medical costs for the patient and society. The guidelines recommend both clinical and preventive strategies for diabetes management and are regularly updated. The aim of the study is to assess the level of adherence of physicians to American Diabetes Association Guidelines. Method: Observational multicenter retrospective study will be conducted among different hospitals in the central region. Patient data will be collected from the records of the last three years (2017- 2020). Records will be selected randomly after a complete randomized design. The study focuses on the management of type 2 according to ADA not changed in the last three updating; those standards; all patients should be taking Metformin 1500 to 2000 mg/day as recommended dose and should be received a high dose of statin if the high risk to ASCVD or moderate statin if not at risk, patients with hypertension and diabetes should taking ACE or ARBS. Result: The study aimed to evaluate the commitment of physicians in the central region to the ADA. Out of the 153 selected patients, only 17 % were able to control their diabetes with an average A1c below 7. ADA stated that to reach the minimum benefit of using Metformin, the daily dose should be between 1500 and 2000 mg. Results showed that 110 patients were on Metformin, where 68% of them were on the recommended dose. ADA recommended the intake of high statin for diabetic patients with ASCVD risk, while diabetic patients without ASCVD risk should be on a moderate statin. Results showed that 61.5% of patients with ASCVD risk were at high statin while only 36% of patients without ASCVD risk were at moderate statin. Results showed that 89 patients have hypertension, and 80% of them are getting ACE/ARBs as recommended by the ADA. Recommendation: It is necessary to implement periodic training courses for some physicians to enhance and update their knowledge.Keywords: American Diabetic Association, diabetes mellitus, atherosclerotic cardiovascular disease, ACE inhibitors
Procedia PDF Downloads 84393 Raw Japanese Quail Egg Produces Analgesic, Anti-Inflammatory and Gastro-Protective Effects in Rats
Authors: Sani Ismaila, Shafiu Yau, Abubakar Salisu, Buhari Salisu, Sharifat Balogun, Mustapha Abubakar, Biobaku Khalid, Agaie Bello
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Over the years, Japanese quail egg has been in use in the management of diseases. The objective of this study was to evaluate the analgesic, anti-inflammatory and gastroprotective effects of raw Quail egg (yolk + albumin) in rats. Pain was assessed in rats by recording the latent period and writing reflex, anti-inflammatory effect was determined using both motility and compression test, while the gastro-protective effects were assessed by observing the histology of the stomach after diclofenac-induced gastric ulcers and subsequent treatment with the quail egg, Rats were randomly assigned into 4 groups; Groups I: were the control non-treated (NT), Group II were treated with Tramadol 50 mg/kg/Os (TMD) or Indomethacin (IND) 5mg/kg/Os (positive control for the writhing reflex determination), while group III and IV were treated with 3 and 6g/kg of raw quail egg respectively). Groups treated with quail egg in both doses showed a significant increase in the latent period (p <0 .05) when compared to the control NT, but lower than the group treated with tramadol at 20mins interval (p<0.05). Writing reflexes decrease in groups II, III, and IV compared to the NT group (p < 0.05). While motility increases significantly (p < 0.05) in groups II, compared to I (p<0.05). Control non-treated rats showed a quicker and extensive response to compression using the Vanier calliper on the inflamed paw compared to groups II-IV (p < 0.05). Histological studies of the stomach revealed sloughing of the epithelia, cellular infiltration with micro abscesses in the non-treated, while groups treated concurrently with quail egg showed proliferation of the glandular epithelia and goblet cells, and those treated 30 minutes before diclofenac administration showed proliferation of glands and thickening of the squamous epithelia. This study showed that quail egg has analgesic, anti-inflammatory and gastro-protective potentials and can be used as adjuvant treatment whenever COX-2 enzymes inhibitors are indicated.Keywords: analgesia, anti-inflammatory, gastroprotective effect, japanese quail egg
Procedia PDF Downloads 383392 Haematological Responses on Amateur Cycling Stages Race
Authors: Renato André S. Silva, Nana L. F. Sampaio, Carlos J. G. Cruz, Bruno Vianna, Flávio O. Pires
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multiple stage bicycle races require high physiological loads from professional cyclists. Such demands can lead to immunosuppression and health problems. However, in this type of competition, little is known about its physiological effects on amateur athletes, who generally receive less medical support. Thus, this study analyzes the hematological effects of a multiple stage bicycle race on amateur cyclists. Seven Brazilian national amateur cyclists (34 ± 4.21 years) underwent a laboratory test to evaluate VO2Max (69.89 ± 7.43 ml⋅kg-1⋅min-1). Six days later, these volunteers raced in the Tour of Goiás, participating in five races in four days (435 km) of competition. Arterial blood samples were collected one day before and one day after the competition. The Kolmogorov-Smirnov tests were used to evaluate the data distribution and Wilcoxon to compare the two moments (p <0.05) of data collection. The results show: Red cells ↓ 7.8% (5.1 ± 0.28 vs 4.7 ± 0.37 106 / mm 3, p = 0.01); Hemoglobin ↓ 7.9% (15.1 ± 0.31 vs 13.9 ± 0.27 g / dL, p = 0.01); Leukocytes ↑ 9.5% (4946 ± 553 versus 5416 ± 1075 / mm 3, p = 0.17); Platelets ↓ 7.0% (200.2 ± 51.5 vs 186.1 ± 39.5 / mm 3, p = 0.01); LDH ↑ 11% (164.4 ± 28.5 vs 182.5 ± 20.5 U / L, p = 0.17); CK ↑ 13.5% (290.7 ± 206.1 vs 330.1 ± 90.5 U / L, p = 0.39); CK-MB ↑ 2% (15.7 ± 3.9 vs. 20.1 ± 2.9 U / L, p = 0.06); Cortizol ↓ 13.5% (12.1 ± 2.4 vs 9.9 ± 1.9 μg / dL, p = 0.01); Total testosterone ↓ 7% (453.6 ± 120.1 vs 421.7 ± 74.3 ng / dL, p = 0.12); IGF-1 ↓ 15.1% (213.8 ± 18.8 vs 181.5 ± 34.7 ng / mL, p = 0.04). This means that there was significant reductions in O2 allocation / transport capacities, vascular injury disruption, and a fortuitous reduction of muscle skeletal anabolism along with maintenance and / or slight elevation of immune function, glucose and lipid energy and myocardial damage. Therefore, the results suggest that no abnormal health effect was identified among the athletes after participating in the Tour de Goiás.Keywords: cycling, health effects, cycling stages races, haematology
Procedia PDF Downloads 198391 Relationship of Epidermal Growth Factor Receptor Gene Mutations Andserum Levels of Ligands in Non-Small Cell Lung Carcinoma Patients
Authors: Abdolamir Allameh, Seyyed Mortaza Haghgoo, Adnan Khosravi, Esmaeil Mortaz, Mihan Pourabdollah-Toutkaboni, Sharareh Seifi
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Non-Small Cell Lung Carcinoma (NSCLC) is associated with a number of gene mutations in epidermal growth factor receptor (EGFR). The prognostic significance of mutations in exons 19 and 21, together with serum levels of EGFR, amphiregulin (AR), and Transforming Growth Factor-alpha (TGF-α) are implicated in diagnosis and treatment. The aim of this study was to examine the relationship of EGFR mutations in selected exons with the expression of relevant ligands in sera samples of NSCLC patients. For this, a group of NSCLC patients (n=98) referred to the hospital for lung surgery with a mean age of 59±10.5 were enrolled (M/F: 75/23). Blood specimen was collected from each patient. Besides, formalin fixed paraffin embedded tissues were processed for DNA extraction. Gene mutations in exons 19 and 21 were detected by direct sequencing, following DNA amplification which was done by PCR (Polymerase Chain Reaction). Also, serum levels of EGFR, AR, and TGF-α were measured by ELISA. The results of our study show that EGFR mutations were present in 37% of Iranian NSCLC patients. The most frequently identified mutations were deletions in exon 19 (72.2%) and substitutions in exon 21 (27.8%). The most frequently identified alteration, which is considered as a rare mutation, was the E872K mutation in exon 21, which was found in 90% (9 out of 10) cases. EGFR mutation detected in exon 21 was significantly (P<0.05) correlated with the levels of its ligands, EGFR and TGF-α in serum samples. Furthermore, it was found that increased serum AR (>3pg/ml) and TGF-α (>10.5 pg/ml) were associated with shorter overall survival (P<0.05). The results clearly showed a close relationship between EGFR mutations and serum EGFR and serum TGF-α. Increased serum EGFR was associated with TGF-α and AR and linked to poor prognosis of NSCLC. These findings are implicated in clinical decision-making related to EGFR-Tyrosine kinase inhibitors (TKIs).Keywords: lung cancer, Iranian patients, epidermal growth factor, mutation, prognosis
Procedia PDF Downloads 79390 Clara Cell Secretory Protein 16 Serum Level Decreases in Patients with Non-Smoking-Related Chronic Obstructive Pulmonary Diseases (COPD)
Authors: Lian Wu, Mervyn Merrilees
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Chronic Obstructive Pulmonary Disease (COPD) is a worldwide problem, characterized by irreversible and progressive airflow obstruction. In New Zealand, it is currently the 4th commonest cause of death and exacerbations of COPD are a frequent cause of admission to hospital. Serum levels of Clara cell secretory protein-16 (CC-16) are believed to represent Clara cell toxicity. More recently, CC-16 has been found to be associated with smoker COPD. It is produced almost exclusively by non-ciliated Clara cells in the airways, and its primary function is to protect the lungs against oxidative stress and carcinogenesis. After acute exposure to cigarette smoke, serum levels of CC-16 become elevated. CC16 is a potent natural immune-suppressor and anti-inflammatory agent. In vitro, CC16 inhibits both monocyte and polymorphonuclear neutrophils chemotaxis and phagocytosis. CC16 also inhibits fibroblast chemotaxis. However, the role of CC-16 in non-smoking related COPD is still not clear. In this study, we investigated serum CC-16 levels in non-smoking related COPD. Methods: We compared non-smoker patients with COPD (FEV1<60% of predicted, FEV1/FVC <0.7, n=100) and individuals with normal lung function FEV1≥ 80% of predicted and FEV1/FVC≥ 0.7, n=80). All subjects had no smoking history. CC-16 was measured by ELISA. Results and conclusion: Serum CC-16 levels are reduced in individuals with non-smoking related COPD, and there is a weak correlation with disease severity in non-smoking related COPD group compared to non-smoker controls.Keywords: COPD, CC-16, ELISA, non-smoking-related COPD
Procedia PDF Downloads 379389 Effect of Fatty Acids in Feed on Levels of Antibody Titers and CD4 and CD8 T-Lymphocyte against Newcastle Disease Virus of Vaccinated Broiler Chicken
Authors: Alaa A. Shamaun Al-Abboodi, Yunis A. A. Bapeer
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400 one-day-old male broiler chicks (Ross-308) randomly divided to 2 main groups, 1st main group (GA) was feeding basal diet with medium chain fatty acid (MCFA) at rate of 0.15% and divided to four subgroups, 3 subgroups vaccinated with different routes with Newcastle Disease Virus (NDV) and non-vaccinated group. The 2nd main group (GB) feeding basal diet without MCFA and divided the same as 1st main group. The parameters used in this study included: ND antibody titers at 1, 10, 21, 28, 35 and 42 days of age and values of CD4 and CD8 at 1, 20, 30 and 42 days of age. This experiment detected increase in ND antibodies titers in (G1, G2, G3) groups were fed on basal diet MCFA comparing to groups were fed without adding MCFA (G5, G6, G7) and control groups (G4, G8). The results of cellular immune response (CD4 and CD8) T-cells in broiler chicks indicated that there was obviously significant relationship between dietary Fatty Acid (FA) versus the diet without FA on the level of CD4 parameter, for the entire experimental period. The effect of different ages was statistically significant in creating different values of CD4 level, whereas the CD4 level decreases markedly with age. However, analyzing the data of different vaccination methods, oculonasal method of vaccination led to the highest value of CD4 compared with the oral, S/C and control groups. There were statistical differences in CD8 values due to supplementation of FA versus the basal diet and due to the effect of different age periods. As for the age effect, the CD8 value at 20 days of age was significantly higher than at 42 and 30 days.Keywords: broiler, CD4 and CD8, fatty acids, Newcastle Disease
Procedia PDF Downloads 144388 Dietary Effect of Probiotic Bacteria, Bacillus amyloliquefaciens JFP-2 Isolate from Jeju Island`s Traditional Fermented Food, on Innate Immune Response of Oplegnathus fasciatus Challenged with Vibrio anguillarum
Authors: Dong Hwi Kim, Dharaneedharan Subramanian, So Hyun Park, Ha-Ri Choi, Ji-Hyung Kim, Dong-Hoon Lee, Moon Soo Heo
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The present study was performed to evaluate the use of Bacillus amyloliquefaciens JFP-2 isolated from a traditional fermented sea food, as probiotic bacteria in the diets for Rock-bream, Oplegnathus faciatus. A total of 180 fish (187.4 ± 2.7 g) were divided into two groups, control (C) and probiotic (P) group (90 fish per group) in triplicate. C group was fed with basal diet without probiotic, while P group was fed with B. amyloliquefaciens spores at concentration of 1.4 x 106 colony forming units per gram (CFU/g) of feed. After two months of feeding experiments, P group fish showed significant improvements in body weight (BW), weight gain (WG), specific growth rate (SGR) and food conversion ratio (FCR) compared with C group. Also, bi-weekly assessment of serum protein, glucose, fatty acid profile showed a significant increase in probiotic fed fish than that of control fish group. Similar increase in serum antioxidant and lysozyme activity was found in probiotic fed fish group. Twenty days challenge experiment shows decrease mortality in probiotic fed fish group when compared with that of control group. Hence, these results indicate that the use of B. amyloliquefaciens JFP-2 as a feed supplement, is beneficial to improve the health status of Oplegnathus fasciatus challenged with Vibrio anguillarum.Keywords: Bacillus amyloliquefaciens, Oplegnathus fasciatus, probiotic feed, rock bream
Procedia PDF Downloads 258387 Guarding the Fortress: Intellectual Property Rights and the European Union’s Cross-Border Jurisdiction
Authors: Sara Vora (Hoxha)
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The present article delves into the intricate matters concerning Intellectual Property Rights (IPR) and cross-border jurisdiction within the confines of the European Union (EU). The prevalence of cross-border intellectual property rights (IPR) disputes has increased in tandem with the globalization of commerce and the widespread adoption of technology. The European Union (EU) is not immune to this trend. The manuscript presents a comprehensive analysis of various forms of intellectual property rights (IPR), such as patents, trademarks, and copyrights, and the regulatory framework established by the European Union (EU) to oversee these rights. The present article examines the diverse approaches employed for ascertaining the appropriate jurisdiction within the European Union (EU), and their potential application in the sphere of cross-border intellectual property rights (IPR) conflicts. The article sheds light on jurisdictional issues and outcomes of significant cross-border intellectual property rights (IPR) disputes in the European Union (EU). Additionally, the document provides suggestions for effectively managing intellectual property rights conflicts across borders within the European Union, which encompasses the utilization of alternative methods for resolving disputes. The article highlights the significance of comprehending the relevant jurisdiction in the European Union for Intellectual Property Rights (IPR). It also offers optimal approaches for enterprises and individuals who aim to safeguard their intellectual property beyond national boundaries. The primary objective of this article is to furnish a thorough comprehension of Intellectual Property Rights (IPR) and the relevant jurisdiction in the European Union (EU). Additionally, it endeavors to provide pragmatic recommendations for managing cross-border IPR conflicts in this intricate and ever-changing legal milieu.Keywords: intellectual property rights (IPR), cross-border jurisdiction, applicable laws and regulations, dispute resolution, best practices
Procedia PDF Downloads 78386 The Effect of a Weed-Killer Sulfonylurea on Durum Wheat (Triticum Durum Desf)
Authors: L. Meksem Amara, M. Ferfar, N. Meksem, M. R. Djebar
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The wheat is the cereal the most consumed in the world. In Algeria, the production of this cereal covers only 20 in 25 % of the needs for the country, the rest being imported. To improve the efficiency and the productivity of the durum wheat, the farmers turn to the use of pesticides: weed-killers, fungicides and insecticides. However this use often entrains losses of products more at least important contaminating the environment and all the food chain. Weed-killers are substances developed to control or destroy plants considered unwanted. That they are natural or produced by the human being (molecule of synthesis), the absorption and the metabolization of weed-killers by plants cause the death of these plants. In this work, we set as goal the evaluation of the effect of a weed-killer sulfonylurea, the CossackOD with various concentrations (0, 2, 4 and 9 µg) on variety of Triticum durum: Cirta. We evaluated the plant growth by measuring the leaves and root length, compared with the witness as well as the content of proline and analyze the level of one of the antioxydative enzymes: catalase, after 14 days of treatment. Sulfonylurea is foliar and root weed-killers inhibiting the acetolactate synthase: a vegetable enzyme essential to the development of the plant. This inhibition causes the ruling of the growth then the death. The obtained results show a diminution of the average length of leaves and roots this can be explained by the fact that the ALS inhibitors are more active in the young and increasing regions of the plant, what inhibits the cellular division and talks a limitation of the foliar and root’s growth. We also recorded a highly significant increase in the proline levels and a stimulation of the catalase activity. As a response to increasing the herbicide concentrations a particular increases in antioxidative mechanisms in wheat cultivar Cirta suggest that the high sensitivity of Cirta to this sulfonylurea herbicide is related to the enhanced production and oxidative damage of reactive oxygen species.Keywords: sulfonylurea, triticum durum, oxydative stress, toxicity
Procedia PDF Downloads 412385 Study of Hypertension at Sohag City: Upper Egypt Experience
Authors: Aly Kassem, Eman Sapet, Eman Abdelbaset, Hosam Mahmoud
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Objective: Hypertension is an important public health challenge being one of the most common worldwide disease-affecting human. Our aim is to study the clinical characteristics, therapeutic regimens, treatment compliance, and risk factors in a sector of of hypertensive patients at Sohag City. Subject and Methods: A cross sectional study; conducted in Sohag city; it involved 520 patients; males (45.7 %) and females (54.3 %). Their ages ranged between 35-85 years. BP measurements, BMI, blood glucose, Serum creatinine, urine analysis, serum Lipids, blood picture and ECG were done all the studied patients. Results: Hypertension presented more between non-smokers (72.55%), females (54.3%), educated patients (50.99%) and patients with low SES (54.9%). CAD presented in (51.63%) of patients, while laboratory investigations showed hyperglycaemia in (28.7%), anemia in (18.3%), high serum creatinine level in (8.49%) and proteinuria in (10.45%) of patient. Adequate BP control was achieved in (49.67%); older patients had lower adequacy of BP control in spite of the extensive use of multiple-drug therapy. Most hypertensive patients had more than one coexistent CV risk factor. Aging, being a female (54.3%), DM (32.3%), family history of hypertension (28.7%), family history of CAD (25.4%), and obesity (10%) were the common contributing risk factors. ACE-inhibitors were prescribed in (58.16%), Beta-blockers in (34.64%) of the patients. Monotherapy was prescribed for (41.17%) of the patients. (75.81%) of patients had regular use of their drug regimens. (49.67%) only of patients had their condition under control, the number of drugs was inversely related to BP control. Conclusion: Hypertensive patients in Sohag city had a profile of high CV risks, and poor blood pressure control particularly in the elderly. A multidisciplinary approach for routine clinical check-up, follow-up, physicians and patients training, prescribing simple once-daily regimens and encouraging life style modifications are recommended. Anti hypertensives, hypertension, elderly patients, risk factors, treatment compliance.Keywords: anti hypertensives, hypertension, elderly patients, risk factors, treatment compliance
Procedia PDF Downloads 304384 Development of a Diagnostic Device to Predict Clinically Significant Inflammation Associated with Cardiac Surgery
Authors: Mohamed Majrashi, Patricia Connolly, Terry Gourlay
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Cardiopulmonary bypass is known to cause inflammatory response during open heart surgery. It includes the initiation of different cascades such as coagulation, complement system and cytokines. Although the immune system is body’s key defense mechanism against external assault, when overexpressed, it can be injurious to the patient, particularly in a cohort of patients in which there is a heightened and uncontrolled response. The inflammatory response develops in these patients to an exaggerated level resulting in an autoimmune injury and may lead to poor postoperative outcomes (systemic inflammatory response syndrome and multi-organs failure). Previous studies by this group have suggested a correlation between the level of IL6 measured in patient’s blood before surgery and after polymeric activation and the observed inflammatory response during surgery. Based upon these findings, the present work is aimed at using this response to develop a test which can be used prior to the open heart surgery to identify the high-risk patients before their operation. The work will be accomplished via three main clinical phases including some pilot in-vitro studies, device development and clinical investigation. Current findings from studies using animal blood, employing DEHP and DEHP plasticized PVC materials as the activator, support the earlier results in patient samples. Having established this relationship, ongoing work will focus on developing an activated lateral flow strip technology as a screening device for heightened inflammatory propensity.Keywords: cardiopulmonary bypass, cytokines, inflammatory response, overexpression
Procedia PDF Downloads 283383 Systematic Review of Current Best Practice in the Diagnosis and Treatment of Obsessive Compulsive Disorder
Authors: Zahra R. Almansoor
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Background: Selective serotonin reuptake inhibitors (SSRI’s) and cognitive behavioural therapy (CBT) are the main treatment methods used for patients with obsessive compulsive disorder (OCD) under the National Institute of Health and Care Excellence (NICE) guidelines. Yet many patients are left with residual symptoms or remit, so several other therapeutic approaches have been explored. Objective: The objective was to systematically review the available literature regarding the treatment efficacy of current and potential approaches and diagnostic strategies. Method: First, studies were examined concerning diagnosis, prognosis, and influencing factors. Then, one reviewer conducted a systematic search of six databases using stringent search terms. Results of studies exploring the efficacy of treatment interventions were analysed and compared separately for adults and children. This review was limited to randomised controlled trials (RCT’s) conducted from 2016 onwards, and an improved Y-BOCS (Yale- Brown obsessive compulsive scale) score was the primary outcome measure. Results: Technology-based interventions including internet-based cognitive behavioural therapy (iCBT) were deemed as potentially effective. Discrepancy remains about the benefits of SSRI use past one year, but potential medication adjuncts include amantadine. Treatments such as association splitting and family and mindfulness strategies also have future potential. Conclusion: A range of potential therapies exist, either as treatment adjuncts to current interventions or as sole therapies. To further improve efficacy, it may be necessary to remodel the current NICE stepped-care model, especially regarding the potential use of lower intensity, cheaper treatments, including iCBT. Although many interventions show promise, further research is warranted to confirm this.Keywords: family and group treatment, mindfulness strategies, novel treatment approaches, standard treatment, technology-based interventions
Procedia PDF Downloads 118382 Gene Expression Signature-Based Chemical Genomic to Identify Potential Therapeutic Compounds for Colorectal Cancer
Authors: Yen-Hao Su, Wan-Chun Tang, Ya-Wen Cheng, Peik Sia, Chi-Chen Huang, Yi-Chao Lee, Hsin-Yi Jiang, Ming-Heng Wu, I-Lu Lai, Jun-Wei Lee, Kuen-Haur Lee
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There is a wide range of drugs and combinations under investigation and/or approved over the last decade to treat colorectal cancer (CRC), but the 5-year survival rate remains poor at stages II–IV. Therefore, new, more efficient drugs still need to be developed that will hopefully be included in first-line therapy or overcome resistance when it appears, as part of second- or third-line treatments in the near future. In this study, we revealed that heat shock protein 90 (Hsp90) inhibitors have high therapeutic potential in CRC according to combinative analysis of NCBI's Gene Expression Omnibus (GEO) repository and chemical genomic database of Connectivity Map (CMap). We found that second generation Hsp90 inhibitor, NVP-AUY922, significantly down regulated the activities of a broad spectrum of kinases involved in regulating cell growth arrest and death of NVPAUY922-sensitive CRC cells. To overcome NVP-AUY922-induced upregulation of survivin expression which causes drug insensitivity, we found that combining berberine (BBR), a herbal medicine with potency in inhibiting survivin expression, with NVP-AUY922 resulted in synergistic antiproliferative effects for NVP-AUY922-sensitive and -insensitive CRC cells. Furthermore, we demonstrated that treatment of NVP-AUY922-insensitive CRC cells with the combination of NVP-AUY922 and BBR caused cell growth arrest through inhibiting CDK4 expression and induction of microRNA-296-5p (miR-296-5p)-mediated suppression of Pin1–β-catenin–cyclin D1 signaling pathway. Finally, we found that the expression level of Hsp90 in tumor tissues of CRC was positively correlated with CDK4 and Pin1 expression levels. Taken together, these results indicate that combination of NVP-AUY922 and BBR therapy can inhibit multiple oncogenic signaling pathways of CRC.Keywords: berberine, colorectal cancer, connectivity map, heat shock protein 90 inhibitor
Procedia PDF Downloads 303381 Knowledge Sharing Practices in the Healthcare Sector: Evidences from Primary Health Care Organizations in Indonesia
Authors: Galih Imaduddin
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Knowledge has been viewed as one of the most important resources in organizations, including those that operate in the healthcare sector. On that basis, Knowledge Management (KM) is crucial for healthcare organizations to improve their productivity and ensure effective utilization of their resources. Despite the growing interests to understand how KM might work for healthcare organizations, there is only a modest amount of empirical inquiries which have specifically focused on the tools and initiatives to share knowledge. Hence, the main purpose of this paper is to investigate the way healthcare organizations, particularly public sector ones, utilize knowledge sharing tools and initiatives for the benefit of patient-care. Employing a qualitative method, 13 (thirteen) Community Health Centers (CHCs) from a high-performing district health setting in Indonesia were observed. Data collection and analysis involved a repetition of document retrievals and interviews (n=41) with multidisciplinary health professionals who work in these CHCs. A single case study was cultivated reflecting on the means that were used to share knowledge, along with the factors that inhibited the exchange of knowledge among those health professionals. The study discovers that all of the thirteen CHCs exhibited and applied knowledge sharing means which included knowledge documents, virtual communication channels (i.e. emails and chatting applications), and social learning forums such as staff meetings, morning briefings, and communities of practices. However, the intensity of utilization was different among these CHCs, in which organizational culture, leadership, professional boundaries, and employees’ technological aptitude were presumed to be the factors that inhibit knowledge sharing processes. Making a distance with the KM literature of other sectors, this study denounces the primacy of technology-based tools, suggesting that socially-based initiatives could be more reliable for sharing knowledge. This suggestion is largely due to the nature of healthcare work which is still predominantly based on the tacit form of knowledge.Keywords: knowledge management, knowledge sharing, knowledge sharing tools and initiatives, knowledge sharing inhibitors, primary health care organizations
Procedia PDF Downloads 243380 Disseminated Tuberculosis: Experience from Tuberculosis Directly Observed Treatment Short Course Center at a Tertiary Care Teaching Hospital in the Philippines
Authors: Jamie R. Chua, Christina Irene D. Mejia, Regina P. Berba
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Disseminated tuberculosis is an infectious disease caused by Mycobacterium tuberculosis involving two or more non-contiguous sites identified through bacteriologic confirmation or clinical diagnosis. Over the five year period included in the study, the UP-PGH TB DOTS clinic had total of 3,967 referrals, and the prevalence of disseminated tuberculosis is 1% (68/3967). The mean age was 33.9 years (range 19-64 years) with a male: female ratio of 1:1. 67% (52 patients) had no predisposing comorbid illness or immune disorder. The most common presenting symptoms were abdominal pain (19%), back pain (13%), abdominal enlargement (11%) and mass (10.2%). Anemia, leukocytosis, hypoalbuminemia, and high-normal serum calcium were common biochemical and hematologic findings. Around 36% (25) of patients were diagnosed clinically with disseminated tuberculosis despite lacking bacteriologic evidence of multi-organ involvement. The lungs (86%) is still the most commonly involved site, followed by intestinal (22%), vertebral/Pott’s (27%), and pelvic/genital (19%). The mean time from presentation to initiation of therapy was 22 days (SD 32.7). Only 18 patients (29.3%) were properly recorded to have been referred to local TB DOTs facilities. Of the 68 patients, only 16% (11 patients) continued follow-up at PGH, and all had documented treatment completion. Treatment outcomes of the remaining were unknown. Due to the variety of involved sites, a high index of suspicion is required. Knowledge on clinical features, common radiographic findings, and histopathologic characteristics of disseminated TB is important as bacteriologic evidence of infection is not always apparent.Keywords: disseminated tuberculosis, Mycobacterium tuberculosis, miliary tuberculosis, tuberculosis
Procedia PDF Downloads 239379 Ipsilateral Heterotopic Ossification in the Knee and Shoulder Post Long COVID-19
Authors: Raheel Shakoor Siddiqui, Calvin Mathias, Manikandar Srinivas Cheruvu, Bobin Varghese
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A 58 year old gentleman presented to accident and emergency at the district general hospital with worsening shortness of breath and a non-productive cough over a period of five days. He was initially admitted under the medical team for suspicion of SARS-CoV-2 (COVID-19) pneumonitis. Subsequently, upon deterioration of observations and a positive COVID-19 PCR, he was taken to intensive care for invasive mechanical ventilation. He required frequent proning, inotropic support and was intubated for thirty-three days. After successful extubation, he developed myopathy with a limited range of motion to his right knee and right shoulder. Plain film imaging of these limbs demonstrated an unusual formation of heterotopic ossification without any precipitating trauma or surgery. Current literature demonstrates limited case series portraying heterotopic ossification post-COVID-19. There has been negligible evidence of heterotopic ossification in the ipsilateral knee and shoulder post-prolonged immobility secondary to a critical illness. Physiotherapy and rehabilitation are post-intensive care can be prolonged due to the formation of heterotopic ossification around joints. Prolonged hospital stays may lead to a higher risk of developing infections of the chest, urine and pressure sores. This raises the question of whether a severe systemic inflammatory immune response from the SARS-CoV-2 virus results in histopathological processes leading to the formation of heterotopic ossification not previously seen, requiring prolonged physiotherapy.Keywords: orthopaedics, rehabilitation, physiotherapy, heterotopic ossification, COVID-19
Procedia PDF Downloads 69378 Antiulcer Activity of Aloe vera Gel against Indomethacin and Ethanol Induced Gastric Ulcers in Rats
Authors: Jyoti Manandhar Shrestha, Saurab Raj Joshi, Maya Shrestha, Prashanna Shrestha, Kshitij Chaulagain
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Background: The widespread use of non-steroidal anti-inflammatory drugs has increased the incidence of ulcer and serious complications, such as perforation and bleeding. Although, the H2 receptor blockers and proton pump inhibitors decrease the acid secretion and promote healing of ulcer, their value in preventing relapse, recurrence, “acid rebound” after cessation of therapy and associated long term adverse effects limit their utility. So to minimize this, the herbal plant Aloe vera having anti-oxidant, anti-inflammatory, mucus secreting, cyto-protective and healing property is believed to cure the peptic ulcer. Objectives: To observe whether oral treatment with Aloe vera gel can prevent peptic ulcer. Indomethacin and ethanol were used to induce gastric ulcers. Thirty six albino rats of either sex were randomly allotted to six groups of six animals each. The negative control was pretreated with normal saline, the positive controls received ranitidine (20 mg/kg) and the test group received Aloe vera gel (300 mg/kg) orally for eight days. Then, after a 24 hour fast Indomethacin (20 mg/kg) or 80% ethanol (2ml) was administered orally to induce ulceration. At the end of the study, the rats were sacrificed, their stomachs opened, the ulcer index studied and tissues sent for histopathological examination. Results: It was observed that, in indomethacin treated group, the ulcer index in control group was 8.167 ± 1.72.In the Aloe vera pretreated animals, the ulcer index was 2.83 ± 1.72 and the standard ranitidine pretreated group ulcer index was 1.67 ± 1.36. In ethanol treated group, the ulcer index in control group was 7.5 ± 2.73. In the Aloe vera pretreated animals, the ulcer index was 2.67 ± 1.75 and the standard ranitidine pretreated group ulcer index was 1.33±1.21. Both ranitidine and Aloe vera gel significantly prevented stomach from gastric ulceration induced by indomethacin and ethanol. Conclusion: The results indicated that Aloe vera gel is effective against indomethacin and ethanol mediated gastric ulcer.Keywords: Aloe vera gel, ethanol, indomethacin, peptic ulcer, ranitidine
Procedia PDF Downloads 457377 The Microflora Assessment of the Urethra Area of Children with Newly Diagnosed Type 1 Diabetes
Authors: Ewa Rusak, Sebastian Seget, Aleksandra Mroskowiak, Mirosław Partyka, Ewa Samulska, Julia Strózik, Anna Wilk, Przemysława Jarosz-Chobot
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Introduction: Various infections can affect children suffering from Type 1 Diabetes (T1D) because of dysfunctions of the immune system. The urinary tract and urethra of these children can be easily infected areas because of glycosuria. Aim: The microflora assessment of the urethra area of children with newly diagnosed T1D. Methods: The materials of the study were swabs taken prospectively from the urethral area of 63 children at the time of diagnosis of T1D (37 boys), then the results were correlated to the clinical parameters. In the statistical analysis, there were T student, Chi square, and U Mann-Whitney tests used. Results: The mean age was 9.4 years (6 months-17.4 years). The mean HbA1c value was 12.1% (5,6% - 20.1%). The mean value of glycosuria was 4463.2 mg/dl (0 - 9770 mg/dl). Ketoacidosis was diagnosed in 29 children (49%). The following microbial species were isolated in the collected materials: Staphylococcus epidermidis in 18 children (28.6%), Enterococcus faecalis in 17 children (27%), Candida albicans in 15 children (23.8%), coagulase-negative staphylococciin 11 children (17.5%), group B Streptococcus beta-hemolysis in 10 children (15.9%), S. aureus, E. coli, S. anginosus, C. glucuronolyticum, and A. urinae in 7 children each (11.1%), group B Streptococcus beta-hemolysis and S. hominis in 6 children each (9.5%), L. gasseri in 5 children (7.5%), C. dubliniensis in 4 children (6.3) and other, isolated cases. 2 of diagnosed patients were cultured negatively (3.2%). There were statistical correlations between the type of colonisation and patients’ sex and HbA1C value. Conclusions: It is extremely important to examine the urethral area at the time of diagnosis of T1D in order to detect inflammation and to undertake the appropriate and effective intervention.Keywords: diabetology, skin disorders, microbiology, microflora
Procedia PDF Downloads 142376 Expression of Gro-El under Phloem-Specific Promoter Protects Transgenic Plants against Diverse Begomovirus-Beta Satellite Complex
Authors: Muhammad Yousaf Ali, Shahid Mansoor, Javeria Qazi, Imran Amin, Musarrat Shaheen
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Cotton leaf curl disease (CLCuD) is the major threat to the cotton crop and is transmitted by whitefly (Bemisia tabaci). Since multiple begomoviruses and associated satellites are involved in CLCuD, approaches based on the concept of broad-spectrum resistance are essential for effective disease control. Gro-El and G5 are two proteins from whitefly endosymbiont and M13 bacteriophage origin, respectively. Gro-El encapsulates the virus particle when it enters the whitefly and protects the virus from the immune system of the whitefly as well as prevents viral expression in it. This characteristic of Gro-El can be exploited to get resistance against viruses if expressed in plants. G5 is a single-stranded DNA binding protein, expression of which in transgenic plants will stop viral expression on its binding with ssDNA. The use of tissue-specific promoters is more efficient than constitutive promoters. Transgenics of Nicotiana benthamiana for Gro-El under constitutive promoter and Gro-El under phloem specific promoter were made. In comparison to non-transgenic plants, transgenic plants with Gro-El under NSP promoter showed promising results when challenged against cotton leaf curl Multan virus (CLCuMuV) along with cotton leaf curl Multan beta satellite (CLCuMB), cotton leaf curl Khokhran virus (CLCuKoV) along with cotton leaf curl Multan beta satellite (CLCuMB) and Pedilenthus leaf curl virus (PedLCV) along with Tobacco leaf curl beta satellite (TbLCB).Keywords: cotton leaf curl disease, whitefly, endosymbionts, transgenic, resistance
Procedia PDF Downloads 95375 The Influence of Immunity on the Behavior and Dignity of Judges
Authors: D. Avnieli
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Immunity of judges from liability represents a departure from the principle that all are equal under the law, and that victims may be granted compensation from their offenders. The purpose of the study is to determine if judicial immunity coincides with the need to ensure the existence of highly independent and incorruptible judiciary. Judges are immune from civil and criminal liability for their judicial acts. Judicial immunity is justified by the need to maintain complete independence and discretion of the judiciary. Scholars and judges believe that absolute immunity is needed to shield judges from pressures, threats, or outside interference. It is commonly accepted, that judges should be free to perform their judicial role in accordance with their assessment of the fact and their understanding of the law, without any restrictions, influences, inducements or interferences. In most countries, immunity applies when judges act in excess of jurisdiction. In some countries, it applies even when they act maliciously or corruptly. The only exception to absolute immunity applicable in all judicial systems is when judges act without jurisdiction over the subject matter. The Israeli Supreme Court recently decided to embrace absolute immunity and strike off a lawsuit of a refugee, who was unlawfully incarcerated. The Court ruled that the plaintiff cannot sue the State or the judge for damages. The questions of malice, dignity, and public scrutiny were not discussed. This paper, based on comparative analysis of many cases, aims to determine if immunity affects the dignity and behavior of judges. It demonstrates that most judges maintain their dignity and ethical code of behavior, but sometimes do not hesitate to act consciously in excess of jurisdiction, and in rare cases even corruptly. Therefore, in order to maintain independent and incorruptible judiciary, immunity should not be applied where judges act consciously in excess of jurisdiction or with malicious incentives.Keywords: incorruptible judiciary, immunity, independent, judicial, judges, jurisdiction
Procedia PDF Downloads 102374 Study of Age-Dependent Changes of Peripheral Blood Leukocytes Apoptotic Properties
Authors: Anahit Hakobjanyan, Zdenka Navratilova, Gabriela Strakova, Martin Petrek
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Aging has a suppressive influence on human immune cells. Apoptosis may play important role in age-dependent immunosuppression and lymphopenia. Prevention of apoptosis may be promoted by BCL2-dependent and BCL2-independent manner. BCL2 is an antiapoptotic factor that has an antioxidative role by locating the glutathione at mitochondria and repressing oxidative stress. STAT3 may suppress apoptosis in BCL2-independent manner and promote cell survival blocking cytochrome-c release and reducing ROS production. The aim of our study was to estimate the influence of aging on BCL2-dependent and BCL2-independent prevention of apoptosis via measurement of BCL2 and STAT3 mRNAs expressions. The study was done on Armenian population (2 groups: 37 healthy young (mean age±SE; min/max age, male/female: 37.6±1.1; 20/54, 15/22), 28 healthy aged (66.7±1.5; 57/85, 12/16)). mRNA expression in peripheral blood leukocytes (PBL) was determined by RT-PCR using PSMB2 as the reference gene. Statistical analysis was done with Graph-Pad Prism 5; P < 0.05 considered as significant. The expression of BCL2 mRNA was lower in aged group (0.199) compared with young ones (0.643)(p < 0.01). Decrease expression was also recorded for female and male subgroups (p < 0.01). The expression level of STAT3 mRNA was increased (young, 0.228; aged, 0.428) (p < 0.05) during aging (in the whole age group and male/female subgroups). Decreased level of BCL2 mRNA may indicate about the suppression of BCL2-dependent prevention of apoptosis during aging in peripheral blood leukocytes. At the same time increased the level of STAT3 may suggest about activation of BCL2-independent prevention of apoptosis during aging.Keywords: BCL2, STAT3, aging, apoptosis
Procedia PDF Downloads 325373 Study of seum Tumor Necrosis Factor Alpha in Pediatric Patients with Hemophilia A
Authors: Sara Mohammad Atef Sabaika
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Background: The development of factor VIII (FVIII) inhibitor and hemophilic arthropathy in patients with hemophilia A (PWHA) are a great challenge for hemophilia care. Both genetic and environmental factors led to complications in PWHA. The development of inhibitory antibodies is usually induced by the immune response. Tumor necrosis factor α (TNF-α), one of the cytokines, might contribute to its polymorphism. Aim: Study the association between tumor necrosis alpha level and genotypes in pediatric patients with hemophilia A and its relation to inhibitor development and joint status. Methods: A cross-sectional study was conducted among a sufficient number of PWHA attending the Pediatric Hematology and Oncology Unit, Pediatric department in Menoufia University hospital. The clinical parameters, FVIII, FVIII inhibitor, and serum TNF-α level were assessed. The genotyping of −380G > A TNF-α gene polymorphism was performed using real time polymerase chain reaction. Results: Among the 50 PWHA, 28 (56%) were identified as severe PWHA. The FVIII inhibitor was identified in 6/28 (21.5%) of severe PWHA. There was a significant correlation between serum TNF-α level and the development of inhibitor (p = 0:043). There was significant correlation between polymorphisms of −380G > A TNF-α gene and hemophilic arthropathy development (p = 0:645). Conclusion: The prevalence of FVIII inhibitor in severe PWHA in Menoufia was 21.5%. The frequency of replacement therapy is a risk factor for inhibitor development. Serum TNF-α level and its gene polymorphism might be used to predict inhibitor development and joint status in pediatric patients with hemophilia A.Keywords: hemophilic arthropathy, TNF alpha., patients witb hemophilia A PWHA, inhibitor
Procedia PDF Downloads 92372 Indoleamine 2,3 Dioxygenase and Regulatory T Cells in Acute Myeloid Leukemia
Authors: Iman M. Mansour, Rania A. Zayed, Fadwa S. Abdel-Azim, Lamyaa H. Abdel-Latif
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Background and Objectives: The microenvironment of acute myeloid leukemia (AML) is suppressive for immune cells. Regulatory T cells (Tregs) have been recognized to play a role in helping leukemic cells to evade immunesurveillance. The mesenchymal stem cells (MSCs) are essential contributors in immunomodulation of the microenvironment as they can promote differentiation of Tregs via the indoleamine 2,3-dioxygenase (IDO) pathway. The aim of the present work was to evaluate the expression of IDO in bone marrow derived MSCs and to study its correlation to percentage of Tregs. Methods: 37 adult bone marrow samples were cultured in appropriate culture medium to isolate MSCs. Successful harvest of MSCs was determined by plastic adherence, morphology and positive expression of CD271 and CD105; negative expression of CD34 and CD45 using flowcytometry. MSCs were examined for IDO expression by immunocytochemistry using anti-IDO monoclonal antibody. CD4+ CD25+ cells (Tregs) were measured in bone marrow samples by flowcytometry. Results: MSCs were successfully isolated from 20 of the 37 bone marrow samples cultured. MSCs showed higher expression of IDO and Tregs percentage was higher in AML patients compared to control subjects (p=0.002 and p<0.001 respectively). A positive correlation was found between IDO expression and Tregs percentage (p value=0.012, r=0.5). Conclusion: In this study, we revealed an association between high IDO expression in MSCs and elevated levels of Tregs which has an important role in the pathogenesis of AML, providing immunosuppressive microenvironment.Keywords: acute myeloid leukemia, indoleamine 2, 3-dioxygenase, mesenchymal stem cells, T regulatory cells
Procedia PDF Downloads 358371 Separation and Characterization of Micobacterium bovis Cell Surface Lysate Antigen
Authors: Albina V. Moskvicheva, Gevorg G. Kazarian, Anna R. Valeeva, Marina A. Efimova, Malik N. Mukminov, Eduard A. Shuralev, Rustam Kh. Ravilov, Kamil S. Khaertynov
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Improving the early diagnosis of tuberculosis and solving a number of problems associated with the differential diagnosis of Mycobacterium bovis infection, nonspecific tuberculin reactions caused by sensitization of the body by non-tuberculosis mycobacteria, is urgent. The filtrates and extracts of M. bovis cell surface components are promising antigens with diagnostic potential. The purpose of this study was to isolate and characterize antigenic proteins and determine the dominant M. bovis antigens recognized by the humoral immune system. The mycobacterial cells were homogenized on FastPrep-24. Gel-filtration chromatography was used to fractionate the lysates of cell surface component extracts and proteins isolated from M. bovis culture supernatant. The separated fractions were analyzed using two-dimensional gel electrophoresis followed by determination of antigen serological activity using immunoblot with specific hyperimmune rabbit blood serum. As a result of electrophoretic separation of components by molecular weight, 23 antigen fractions were obtained. Analysis of densitograms showed that the fractions contained two zones of antigens with pronounced serological activity, corresponding to molecular weights of 28 and 21 kDa. The high serological activity of the 28 kDa antigen was established by immunoblot using hyperimmune blood sera. Separated and characterized by M. bovis specific antigen with a molecular weight of 28 kDa was added to the collection of specific marker antigens for M. bovis.Keywords: antigen, gel-filtration chromatography, immunoblot, Mycobacterium bovis
Procedia PDF Downloads 134370 Antioxidant Property of Honey with Dried Cherry
Authors: Jasna M. Čanadanović-Brunet, Gordana S. Ćetković, Jelena J. Vulić, Sonja M. Djilas, Vesna T. Tumbas Šaponjac, Sladjana M. Stajčić
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Honey serves as a source of natural antioxidants, which are effective in reducing the risk of heart disease, cancer, immune-system decline, cataracts, different inflammatory processes, and also prevent deteriorative oxidation reactions in foods such as enzymatic browning of fruit and vegetables. Honey is a natural saturated sugar solution, but it also contains certain minor constituents, proteins, enzymes, amino and organic acids, lipids, vitamins, phenolic acids, flavonoids and carotenoids. It is consumed in its natural form alone, but also in combination with nuts and various kinds of dried fruits. The aim of this research was to investigate the contribution of dried cherry on phenols (TPh) and flavonoids (Fl) contents and antioxidant activities of honey. Phenolic compounds in Serbian polyfloral (PH), linden (LH) and acacia (AH) honey and also in their mixtures with dried cherry, in 40% mass concentrations (PH40; LH40, AH40), were determined. In comparison to honey, TPh increased 2.25 times for LH40, 2.16 times for AH40 and 1.45 times for PH40, while Fl increased 2.81-fold for PH40, 1.21-fold for LH40 and 1.44-fold for AH40. Antioxidant activity was investigated with two assays, DPPH test and reducing power (RP), and expressed as EC50DPPH and RP0.5 values. The EC50DPPH values were: EC50PH40 = 1.16 mg/ml; EC50LH40= 1.42 mg/ml and EC50AH40= 1.69 mg/ml, while RP0.5 were: RP0.5PH40 = 15.05 mg/ml; RP0.5LH40 = 16.09 mg/ml and P0.5AH40 = 17.60 mg/ml. Our results indicate that supplementation of polyfloral, linden and acacia honey with 40% dried cherry improves antioxidant activity of honey by enriching the phenolic composition.Keywords: antioxidant activity, dried cherry, honey, phenolics
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