Search results for: anti apoptotic drug
Commenced in January 2007
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Edition: International
Paper Count: 3891

Search results for: anti apoptotic drug

591 Management of Blood Exposure Risk: Knowledge and Attitudes of Caregivers in Pediatric Dapartments

Authors: Hela Ghali, Oumayma Ben Amor, Salwa Khefacha, Mohamed Ben Rejeb, Sirine Frigui, Meriam Tourki Dhidah, Lamine Dhidah, Houyem Said Laatiri

Abstract:

Background: Blood exposure accidents are the most common problem in hospitals that threaten healthcare professionals with a high risk of infectious complications which weighs heavily on health systems worldwide. Paramedics are the highest risk group due to the nature of their daily activities. We aimed to determine knowledge and attitudes about the management of blood-exposure accidents among nurses and technicians in two pediatric departments. Materials/Methods: This is a cross-sectional descriptive study conducted on March 2017, carried out with the care staff of the pediatric ward of the Farhat Hached Teaching Hospital of Sousse and pediatric surgery of the Fattouma Bourguiba University Hospital in Monastir, using a pre- tested and self-administered questionnaire. Data entry and analysis were performed using Excel software. Results: The response rate was 85.1%. A female predominance (82.5%) was reported among respondents with a sex ratio of 0.21. 80% of the participants were under 35 years old. Seniority of less than 10 years was found in 77.5% of respondents. Only 22.5% knew the definition of a blood- exposure accident. 100% and 95% of participants reported the relative risk, respectively, to hepatitis and AIDS viruses. However, only 15% recognized the severity factors of a blood-exposure accident. Hygiene compliance was the most important dimension for almost the entire population for the prevention. On the other hand, only 12.5% knew the meaning of 'standard precautions' and ¼ considered them necessary for at-risk patients only. 40% reported being exposed at least once, among them, 87.5% used betadine, and 77.5% said that anti-infectious chemoprophylaxis is necessary regardless of the patient's serological status. However, 52.5% did not know the official reporting circuit of management of blood-exposure accident in their institutions. Conclusion: For better management of risks in hospitals and an improvement of the safety of the care, a reinforcement of the sensibilization of the caregivers with regard to the risks of blood exposure accident is necessary, while developing their knowledge to act in security.

Keywords: attitudes, blood-exposure accident, knowledge, pediatric department

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590 Simulation of the FDA Centrifugal Blood Pump Using High Performance Computing

Authors: Mehdi Behbahani, Sebastian Rible, Charles Moulinec, Yvan Fournier, Mike Nicolai, Paolo Crosetto

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Computational Fluid Dynamics blood-flow simulations are increasingly used to develop and validate blood-contacting medical devices. This study shows that numerical simulations can provide additional and accurate estimates of relevant hemodynamic indicators (e.g., recirculation zones or wall shear stresses), which may be difficult and expensive to obtain from in-vivo or in-vitro experiments. The most recent FDA (Food and Drug Administration) benchmark consisted of a simplified centrifugal blood pump model that contains fluid flow features as they are commonly found in these devices with a clear focus on highly turbulent phenomena. The FDA centrifugal blood pump study is composed of six test cases with different volumetric flow rates ranging from 2.5 to 7.0 liters per minute, pump speeds, and Reynolds numbers ranging from 210,000 to 293,000. Within the frame of this study different turbulence models were tested including RANS models, e.g. k-omega, k-epsilon and a Reynolds Stress Model (RSM) and, LES. The partitioners Hilbert, METIS, ParMETIS and SCOTCH were used to create an unstructured mesh of 76 million elements and compared in their efficiency. Computations were performed on the JUQUEEN BG/Q architecture applying the highly parallel flow solver Code SATURNE and typically using 32768 or more processors in parallel. Visualisations were performed by means of PARAVIEW. Different turbulence models including all six flow situations could be successfully analysed and validated against analytical considerations and from comparison to other data-bases. It showed that an RSM represents an appropriate choice with respect to modeling high-Reynolds number flow cases. Especially, the Rij-SSG (Speziale, Sarkar, Gatzki) variant turned out to be a good approach. Visualisation of complex flow features could be obtained and the flow situation inside the pump could be characterized.

Keywords: blood flow, centrifugal blood pump, high performance computing, scalability, turbulence

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589 Cytotoxicity of 13 South African Macrofungal Species and Mechanism/s of Action against Cancer Cell Lines

Authors: Gerhardt Boukes, Maryna Van De Venter, Sharlene Govender

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Macrofungi have been used for the past two thousand years in Asian countries, and more recently in Western countries, for their medicinal properties. Biological activities include antimicrobial, antioxidant, anti-inflammatory, antidiabetic, anticancer and immunomodulatory to name a few. Several biologically active compounds have been identified and isolated. Macrofungal research in Africa is poorly documented and to the best of our knowledge non-existent. South Africa has a rich macrofungal biodiversity, which includes endemic and exotic macrofungal species. Ethanolic extracts of 13 macrofungal species, including mushrooms, bracket fungi and puffballs, were prepared and screened for cytotoxicity against a panel of seven cell lines, including A549 (human lung adenocarcinoma), HeLa (human cervical adenocarcinoma), HT-29 (human colorectal adenocarcinoma), MCF7 (human breast adenocarcinoma), MIA PaCa-2 (human pancreatic ductal adenocarcinoma), PC-3 (human prostate adenocarcinoma) and Vero (African green monkey kidney epithelial) cells using MTT. Cell lines were chosen according to the most prevalent cancer types affecting males and females in South Africa and globally, and the mutations they contain. Preliminary results have shown that three of the macrofungal genera, i.e. Fomitopsis, Gymnopilus and Pycnoporus, have shown cytotoxic activity, ranging between IC50 ~20 and 200 µg/mL. The molecular mechanism of action contributing to cell death investigated and being investigated include apoptosis (i.e. DNA cell cycle arrest, caspase-3 activation and mitochondrial membrane potential), autophagy (i.e. acridine orange and LC3B staining) and ER stress (i.e. thioflavin T staining and caspase-12) in the presence of melphalan, chloroquine and thapsigargin/tuncamycin as positive controls, respectively. The genus, Pycnoporus, has shown the best cytotoxicity of the three macrofungal genera. Future work will focus on the identification and isolation of novel active compounds and elucidating the mechanism/s of action.

Keywords: cancer, cytotoxicity, macrofungi, mechanism/s of action

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588 Efficacy of In-Situ Surgical vs. Needle Revision on Late Failed Trabeculectomy Blebs

Authors: Xie Xiaobin, Zhang Yan, Shi Yipeng, Sun Wenying, Chen Shuang, Cai Zhipeng, Zhang Hong, Zhang Lixia, Xie Like

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Objective: The objective of this research is to compare the efficacy of the late in-situ surgical revision augmented with continuous infusion and needle revision on failed trabeculectomy blebs. Methods From December 2018 to December 2021, a prospective randomized controlled trial was performed on 44 glaucoma patients with failed bleb ≥ 6months with medically uncontrolled in Eye Hospital, China Academy of Chinese Medical Sciences. They were randomly divided into two groups. 22 eyes of 22 patients underwent the late in-situ surgical revision with continuous anterior chamber infusion in the study group, and 22 of 22 patients were treated with needle revision in the control group. Main outcome measures include preoperative and postoperative intraocular pressure (IOP), the number of anti-glaucoma medicines, the operation success rate, and the postoperative complications. Results The postoperative IOP values decreased significantly from the baseline in both groups (both P<0.05). IOP was significantly lower in the study group than in the control group at one week, 1, and 3 months postoperatively (all P<0.05). IOP reductions in the study group were substantially more prominent than in the control group at all postoperative time points (all P<0.05). The complete success rate in the study group was significantly higher than in the control group (71.4% vs. 33.3%, P<0.05), while the complete failure rate was significantly lower in the study group (0% vs. 28.5%, P<0.05). According to Cox’s proportional hazards regression analysis, high IOP at baseline was independently associated with increased risks of complete failure (adjusted hazard ratio=1.141, 95% confidence interval=1.021-1.276, P<0.05). There was no significant difference in the incidence of postoperative complications between the two groups (P>0.05). Conclusion: Both in-situ surgical and needle revision have acceptable success rates and safety for the late failed trabeculectomy blebs, while the former is likely to have a higher level of efficacy over the latter. Needle revision may be insufficient for eyes with low target IOP.

Keywords: glaucoma, trabeculectomy blebs, in-situ surgical revision, needle revision

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587 Dao Din Student Activists: From Hope to Victims under the Thai Society of Darkness

Authors: Siwach Sripokangkul, Autthapon Muangming

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The Dao Din group is a gathering of students from the Faculty of Law, Khon Kaen University, a leading university in the northeast of Thailand. The Dao Din group has been one of the most prominent student movements in the past four decades since the bloody massacre of the 6th of October 1976. The group of student is a movement who gather to oppose and protest against different capitalist-run projects that have impacted upon the environment since 2009. The students have become heroes in Thai society and receive support from various groups, especially the middle class who regard the students as role models for the youth. Subsequently, the Dao Din group has received numerous awards between 2011-2013. However, the Dao Din group opposed the military coup d’état of 2014 and the subsequent military junta. Under the military dictatorship regime (2014-present), security officials have hunted, insulted, arrested, and jailed members of the group many times amidst silence from most of the from the middle class. Therefore, this article posits the question of why the Dao Din group which was once the hero and hope of Thai society, has become a political victim in only a few years. The study methods used are the analysis of documentaries, news articles, and interviews with representatives of the Dao Din group. The author argues that Thailand’s middle class previously demonstrated a positive perception of the Dao Din group precisely because that group had earlier opposed policies of the elected Yingluck Shinawatra government, which most of the middle class already despised. However, once the Dao Din group began to protest against the anti-Yingluck military government, then the middle class turned to harshly criticize the Dao Din group. So it can be concluded that the Thai middle class tends to put its partisan interests ahead of a civil society group which has been critical of elected as well as military administrations. This has led the middle class to support the demolishing of Thai democracy. Such a Thai middle-class characteristic not only poses a strong bulwark for the perpetuation of military rule but also destroys a civil society group (composed of young people) who should be the future hope of the nation rather than under the Thai society of darkness.

Keywords: Dao Din student activists, the military coup d’état of 2014, Thai politics, human rights violations

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586 Liposome Sterile Filtration Fouling: The Impact of Transmembrane Pressure on Performance

Authors: Hercules Argyropoulos, Thomas F. Johnson, Nigel B Jackson, Kalliopi Zourna, Daniel G. Bracewell

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Lipid encapsulation has become essential in drug delivery, notably for mRNA vaccines during the COVID-19 pandemic. However, their sterile filtration poses challenges due to the risk of deformation, filter fouling and product loss from adsorption onto the membrane. Choosing the right filtration membrane is crucial to maintain sterility and integrity while minimizing product loss. The objective of this study is to develop a rigorous analytical framework utilizing confocal microscopy and filtration blocking models to elucidate the fouling mechanisms of liposomes as a model system for this class of delivery vehicle during sterile filtration, particularly in response to variations in transmembrane pressure (TMP) during the filtration process. Experiments were conducted using fluorescent Lipoid S100 PC liposomes formulated by micro fluidization and characterized by Multi-Angle Dynamic Light Scattering. Dual-layer PES/PES and PES/PVDF membranes with 0.2 μm pores were used for filtration under constant pressure, cycling from 30 psi to 5 psi and back to 30 psi, with 5, 6, and 5-minute intervals. Cross-sectional membrane samples were prepared by microtome slicing and analyzed with confocal microscopy. Liposome characterization revealed a particle size range of 100-140 nm and an average concentration of 2.93x10¹¹ particles/mL. Goodness-of-fit analysis of flux decline data at varying TMPs identified the intermediate blocking model as most accurate at 30 psi and the cake filtration model at 5 psi. Membrane resistance analysis showed atypical behavior compared to therapeutic proteins, with resistance remaining below 1.38×10¹¹ m⁻¹ at 30 psi, increasing over fourfold at 5 psi, and then decreasing to 1-1.3-fold when pressure was returned to 30 psi. This suggests that increased flow/shear deforms liposomes enabling them to more effectively navigate membrane pores. Confocal microscopy indicated that liposome fouling mainly occurred in the upper parts of the dual-layer membrane.

Keywords: sterile filtration, membrane resistance, microfluidization, confocal microscopy, liposomes, filtration blocking models

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585 Targeting Glucocorticoid Receptor Eliminate Dormant Chemoresistant Cancer Stem Cells in Glioblastoma

Authors: Aoxue Yang, Weili Tian, Yonghe Wu, Haikun Liu

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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Little progress has been made in therapeutic treatment of glioblastoma in the last decade despite rapid progress in molecular understanding of brain tumors1. Here we show that the stress hormone glucocorticoid is essential for the maintenance of brain tumor stem cells (BTSCs), which are resistant to conventional therapy. The glucocorticoid receptor (GR) regulates metabolic plasticity and chemoresistance of the dormant BTSC via controlling expression of GPD1 (glycerol-3-phosphate dehydrogenase 1), which is an essential regulator of lipid metabolism in BTSCs. Genomic, lipidomic and cellular analysis confirm that GR/GPD1 regulation is essential for BTSCs metabolic plasticity and survival. We further demonstrate that the GR agonist dexamethasone (DEXA), which is commonly used to control edema in glioblastoma, abolishes the effect of chemotherapy drug temozolomide (TMZ) by upregulating GPD1 and thus promoting tumor cell dormancy in vivo, this provides a mechanistic explanation and thus settle the long-standing debate of usage of steroid in brain tumor patient edema control. Pharmacological inhibition of GR/GPD1 pathway disrupts metabolic plasticity of BTSCs and prolong animal survival, which is superior to standard chemotherapy. Patient case study shows that GR antagonist mifepristone blocks tumor progression and leads to symptomatic improvement. This study identifies an important mechanism regulating cancer stem cell dormancy and provides a new opportunity for glioblastoma treatment.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides.

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584 Effect of Lowering the Proportion of Chlorella vulgaris in Fish Feed on Tilapia's Immune System

Authors: Hamza A. Pantami, Khozizah Shaari, Intan S. Ismail, Chong C. Min

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Introduction: Tilapia is the second-highest harvested freshwater fish species in Malaysia, available in almost all fish farms and markets. Unfortunately, tilapia culture in Malaysia is highly affected by Aeromonas hydrophila and Streptococcus agalactiae, which affect the production rate and consequently pose a direct negative economic impact. Reliance on drugs to control or reduce bacterial infections has been led to contamination of water bodies and development of drug resistance, as well as gave rise to toxicity issues in downstream fish products. Resorting to vaccines have helped curb the problem to a certain extent, but a more effective solution is still required. Using microalgae-based feed to enhance the fish immunity against bacterial infection offers a promising alternative. Objectives: This study aims to evaluate the efficacy of Chlorella vulgaris at lower percentage incorporation in feeds for an immune boost of tilapia in a shorter time. Methods: The study was in two phases. The safety concentration studies at 500 mg/kg-1 and the administration of cultured C. vulgaris biomass via incorporation into fish feed for five different groups in three weeks. Group 1 was the control (0% incorporation), whereas group 2, 3, 4 and 5 received 0.625%, 1.25%, 2.5% and 5% incorporation respectively. The parameters evaluated were the blood profile, serum lysozyme activity (SLA), serum bactericidal activity (SBA), phagocytosis activity (PA), respiratory burst activity (RBA), and lymphoproliferation activity (LPA). The data were analyzed via ANOVA using SPSS (version 16). Further testing was done using Tukey’s test. All tests were performed at the 95% confidence interval (p < 0.05). Results: There were no toxic signs in tilapia fish at 500 mg/kg-1. Treated groups showed significantly better immune parameters compared to the control group (p < 0.05). Conclusions: C. vulgaris crude biomass in a fish meal at a lower incorporation level of 5% can increase specific and non-specific immunity in tilapia fish in a shorter time duration.

Keywords: Chlorella vulgaris, hematology profile, immune boost, lymphoproliferation

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583 Effect of Aquatic Seed Extract of (Cichorium intybus L.) and Metformin on Nitric Oxide in Type 2 Diabetic Rats

Authors: Lotfollah Rezagholizadeh

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Background and Aim: Diabetes mellitus is related to high mortality and morbidity caused by the early development of atherosclerosis correlated to diabetic macroangiopathy. The endothelium-derived vasodilator, nitric oxide (NO) has been implicated in the development of vascular complications via the regulation of blood flow, and various antiatherosclerotic actions. Patients with type 2 diabetes (T2D) have a decreased level of endothelial nitric oxide release. In this study we aimed to examine the effect of aquatic seed extract of Cichorium intybus L. (chicory) and metformin (a known prescription drug for diabetes) on NO levels in T2D rats. Methods: Five groups of adult male Wistar rats were used (n=6): Non-diabetic controls without extract treatment (Control), Non-diabetic controls with extract treatment (Chicory-control), T2D rats without extract treatment (NIA/STZ), T2D rats treated with the extract (Chicory-NIA/STZ), and T2D groups that received metformin (100 mg/kg) but no extract (Metformin-NIA/STZ). T2D was induced with intraperitoneal (i.p) injection of niacinamide (NIA, 200 mg/kg), 15 min after an i.p administration of streptozotocin (STZ, 55 mg/kg). Lyophilized chicory extract (125 mg/kg) was dissolved in 0.2 ml normal saline and administered one dose a day. The experiments lasted for 3 weeks after the diabetes induction. NO analysis was performed by assay based on the Griess reaction. Data were reported as the mean ± SD and statistical analysis was performed by ANOVA. Results: Serum nitric oxide levels decreased significantly in NIA/STZ group compared with Control and Chicory-control. Treatment with chicory extract caused a significant increase in serum levels of NO in Chicory-NIA/STZ group compare to NIA/STZ group (p<05). Metformin-NIA/STZ group did not show considerable difference when compared with NIA/STZ, with respect to NO levels. In a group of rats made diabetic by STZ alone (type 1 diabetic rats, T1D), chicory did not have a significant ameliorating effect. Conclusion: In this study, we clearly showed a relationship between low serum nitric oxide levels and diabetes mellitus in rats. The increase in serum nitric oxide by chicory extract is an indication of antiatherogenic effect of this plant. Chicory seed extract was more efficient than metformin in improving the NO levels in NO-deficient T2D diabetic rats.

Keywords: type 2 diabetes mellitus, nitric oxide, chicory, metformin

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582 Thulium Laser Vaporisation and Enucleation of Prostate in Patients on Anticoagulants and Antiplatelet Agents

Authors: Abdul Fatah, Naveenchandra Acharya, Vamshi Krishna, T. Shivaprasad, Ramesh Ramayya

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Background: Significant number of patients with bladder outlet obstruction due to BPH are on anti-platelets and anticoagulants. Prostate surgery in this group of patients either in the form of TURP or Open prostatectomy is associated with increased risk of bleeding complications requiring transfusions, packing of the prostatic fossa or ligation or embolization of internal iliac arteries. Withholding of antiplatelets and anticoagulants may be associated with cardiac and other complications. Efficacy of Thulium Laser in the above group of patients was evaluated in terms of peri-operative, postoperative and delayed bleeding complications as well as cardiac events in peri-operative and immediate postoperative period. Methods: 217 patients with a mean age of 68.8 years were enrolled between March 2009 and March 2013 (36 months), and treated for BPH with ThuLEP. Every patient was evaluated at base line according to: Digital Rectal Examination (DRE), prostate volume, Post-Voided volume (PVR), International Prostate Symptoms Score (I-PSS), PSA values, urine analysis and urine culture, uroflowmetry. The post operative complications in the form of drop in hemoglobin level, transfusion rates, post –operative cardiac events within a period of 30 days, delayed hematuria and events like deep vein thrombosis and pulmonary embolism were noted. Results: Our data showed a better post-operative outcome in terms of, postoperative bleeding requiring intervention 7 (3.2%), transfusion rate 4 (1.8%) and cardiac events within a period of 30 days 4(1.8%), delayed hematuria within 6 months 2(0.9 %) compared other series of prostatectomies. Conclusion: The thulium LASER prostatectomy is a safe and effective option for patients with cardiac comorbidties and those patients who are on antiplatelet agents and anticoagulants. The complication rate is less as compared to larger series reported with open and transurethral prostatectomies.

Keywords: thulium laser, prostatectomy, antiplatelet agents, bleeding

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581 In vitro α-Amylase and α-Glucosidase Inhibitory Activities of Bitter Melon (Momordica charantia) with Different Stage of Maturity

Authors: P. S. Percin, O. Inanli, S. Karakaya

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Bitter melon (Momordica charantia) is a medicinal vegetable, which is used traditionally to remedy diabetes. Bitter melon contains several classes of primary and secondary metabolites. In traditional Turkish medicine bitter melon is used for wound healing and treatment of peptic ulcers. Nowadays, bitter melon is used for the treatment of diabetes and ulcerative colitis in many countries. The main constituents of bitter melon, which are responsible for the anti-diabetic effects, are triterpene, protein, steroid, alkaloid and phenolic compounds. In this study total phenolics, total carotenoids and β-carotene contents of mature and immature bitter melons were determined. In addition, in vitro α-amylase and α-glucosidase activities of mature and immature bitter melons were studied. Total phenolic contents of immature and mature bitter melon were 74 and 123 mg CE/g bitter melon respectively. Although total phenolics of mature bitter melon was higher than that of immature bitter melon, this difference was not found statistically significant (p > 0.05). Carotenoids, a diverse group of more than 600 naturally occurring red, orange and yellow pigments, play important roles in many physiological processes both in plants and humans. The total carotenoid content of mature bitter melon was 4.36 fold higher than the total carotenoid content of immature bitter melon. The compounds that have hypoglycaemic effect of bitter melon are steroidal saponins known as charantin, insulin-like peptides and alkaloids. α-Amylase is one of the main enzymes in human that is responsible for the breakdown of starch to more simple sugars. Therefore, the inhibitors of this enzyme can delay the carbohydrate digestion and reduce the rate of glucose absorption. The immature bitter melon extract showed α-amylase and α-glucosidase inhibitory activities in vitro. α-Amylase inhibitory activity was higher than that of α-glucosidase inhibitory activity when IC50 values were compared. In conclusion, the present results provide evidence that aqueous extract of bitter melon may have an inhibitory effect on carbohydrate breakdown enzymes.

Keywords: bitter melon, in vitro antidiabetic activity, total carotenoids, total phenols

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580 Attitudes Towards Immigrants: Evidence from Veterans of Colonial Wars in Africa

Authors: Margarida Matos, João Pereira dos Santos, José Tavares

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Anti-minority discrimination is a persistent phenomenon with long-run effects. While there is a vast literature in economics and psychology that shows that personality and beliefs are not fixed and can be altered by experience, particularly in the so-called impressionable years in early adulthood, less is known about the long-lasting impacts of major events occurring during this time on minority attitudes. In this paper, we study the impact of serving in the military on long-term attitudes towards minorities. For many, military conscription and serving in war are unique life-shaping events. In the context of military service, individuals from different socioeconomic backgrounds interact and learn with each other, potentially changing their views and attitudes in a persistent manner. A prominent theory about the change of attitudes is the contact theory. It suggests that prejudice can be decreased if members of the groups interact with one another. The present paper adds to the literature by providing evidence from a more complicated setting involving the exposure to combat. We study the attitudes of veterans of the Portuguese Colonial War between 1961 and 1974, what was the latest war between African independence movements and Europeans. More than 70 percent of military age Portuguese men were drafted every year and sent to fight in Africa in the widest draft in post-World War II Western Europe. The contact between Portuguese and African soldiers was both cooperative as well as adversarial. Portuguese fought against but also alongside locally recruited African men, who represented half of the Portuguese contingent for substantial periods. We use data from the European Social Survey to identify Portuguese citizens likely to have been drafted and were send to fight in the former Portuguese colonies in Africa. We show that men likely to have fought in African wars are more accepting of immigrants than women of their same cohort, as well as than males from younger and older cohorts. The use of corresponding cohorts from Spain as placebo tests confirms our results. Our findings also hold in a regression discontinuity design setting.

Keywords: attitudes, immigration, war in Africa, veterans, portugal

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579 Structural Evolution of Na6Mn(SO4)4 from High-Pressure Synchrotron Powder X-ray Diffraction

Authors: Monalisa Pradhan, Ajana Dutta, Irshad Kariyattuparamb Abbas, Boby Joseph, T. N. Guru Row, Diptikanta Swain, Gopal K. Pradhan

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Compounds with the Vanthoffite crystal structure having general formula Na6M(SO₄)₄ (M= Mg, Mn, Ni , Co, Fe, Cu and Zn) display a variety of intriguing physical properties intimately related to their structural arrangements. The compound Na6Mn(SO4)4 shows antiferromagnetic ordering at low temperature where the in-plane Mn-O•••O-Mn interactions facilitates antiferromagnetic ordering via a super-exchange interaction between the Mn atoms through the oxygen atoms . The inter-atomic bond distances and angles can easily be tuned by applying external pressure and can be probed using high resolution X-ray diffraction. Moreover, because the magnetic interaction among the Mn atoms are super-exchange type via Mn-O•••O-Mn path, the variation of the Mn-O•••O-Mn dihedral angle and Mn-O bond distances under high pressure inevitably affects the magnetic properties. Therefore, it is evident that high pressure studies on the magnetically ordered materials would shed light on the interplay between their structural properties and magnetic ordering. This will indeed confirm the role of buckling of the Mn-O polyhedral in understanding the origin of anti-ferromagnetism. In this context, we carried out the pressure dependent X-ray diffraction measurement in a diamond anvil cell (DAC) up to a maximum pressure of 17 GPa to study the phase transition and determine equation of state from the volume compression data. Upon increasing the pressure, we didn’t observe any new diffraction peaks or sudden discontinuity in the pressure dependences of the d values up to the maximum achieved pressure of ~17 GPa. However, it is noticed that beyond 12 GPa the a and b lattice parameters become identical while there is a discontinuity in the β value around the same pressure. This indicates a subtle transition to a pseudo-monoclinic phase. Using the third order Birch-Murnaghan equation of state (EOS) to fit the volume compression data for the entire range, we found the bulk modulus (B0) to be 44 GPa. If we consider the subtle transition at 12 GPa, we tried to fit another equation state for the volume beyond 12 GPa using the second order Birch-Murnaghan EOS. This gives a bulk modulus of ~ 34 GPa for this phase.

Keywords: mineral, structural phase transition, high pressure XRD, spectroscopy

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578 Development of PVA/polypyrrole Scaffolds by Supercritical CO₂ for Its Application in Biomedicine

Authors: Antonio Montes, Antonio Cozar, Clara Pereyra, Diego Valor, Enrique Martinez de la Ossa

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Tissues and organs can be damaged because of traumatism, congenital illnesses, or cancer and the traditional therapeutic alternatives, such as surgery, cannot usually completely repair the damaged tissues. Tissue engineering allows regeneration of the patient's tissues, reducing the problems caused by the traditional methods. Scaffolds, polymeric structures with interconnected porosity, can be promoted the proliferation and adhesion of the patient’s cells in the damaged area. Furthermore, by means of impregnation of the scaffold with beneficial active substances, tissue regeneration can be induced through a drug delivery process. The objective of the work is the fabrication of a PVA scaffold coated with Gallic Acid and polypyrrole through a one-step foaming and impregnation process using the SSI technique (Supercritical Solvent Impregnation). In this technique, supercritical CO₂ penetrates into the polymer chains producing the plasticization of the polymer. In the depressurization step a CO₂ cellular nucleation and growing to take place to an interconnected porous structure of the polymer. The foaming process using supercritical CO₂ as solvent and expansion agent presents advantages compared to the traditional scaffolds’ fabrication methods, such as the polymer’s high solubility in the solvent or the possibility of carrying out the process at a low temperature, avoiding the inactivation of the active substance. In this sense, the supercritical CO₂ avoids the use of organic solvents and reduces the solvent residues in the final product. Moreover, this process does not require long processing time that could cause the stratification of substance inside the scaffold reducing the therapeutic efficiency of the formulation. An experimental design has been carried out to optimize the SSI technique operating conditions, as well as a study of the morphological characteristics of the scaffold for its use in tissue engineerings, such as porosity, conductivity or the release profiles of the active substance. It has been proved that the obtained scaffolds are partially porous, conductors of electricity and are able to release Gallic Acid in the long term.

Keywords: scaffold, foaming, supercritical, PVA, polypyrrole, gallic acid

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577 Impact of 99mTc-MDP Bone SPECT/CT Imaging in Failed Back Surgery Syndrome

Authors: Ching-Yuan Chen, Lung-Kwang Pan

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Objective: Back pain is a major health problem costing billions of health budgets annually in Taiwan. Thousands of back pain surgeries are performed annually with up to 40% of patients complaining of back pain at time of post-surgery causing failed back surgery syndrome (FBSS), although diagnosis in these patients may be complex. The aim of study is to assess the feasibility of using bone SPECT-CT imaging to localize the active lesions causing persistent, recurrent or new backache after spine surgery. Materials and Methods: Bone SPECT-CT imaging was performed after the intravenous injection of 20 mCi of 99mTc-MDP for all the patients with diagnosis of FBSS. Patients were evaluated using status of subjectively pain relief, functional improvement and degree of satisfaction by reviewing the medical records and questionnaires in a 2 more years’ follow-up. Results: We enrolled a total of 16 patients were surveyed in our hospital from Jan. 2015 to Dec. 2016. Four people on SPEC/CT imaging ensured significant lesions were undergone a revised surgery (surgical treatment group). The mean visual analogue scale (VAS) decreased 5.3 points and mean Oswestry disability index (ODI) improved 38 points in the surgical group. The remaining 12 on SPECT/CT imaging were diagnosed as no significant lesions then received drug treatment (medical treatment group). The mean VAS only decreased 2 .1 point and mean ODI improved 12.6 points in the medical treatment group. In the posttherapeutic evaluation, the pain of the surgical treatment group showed a satisfactory improvement. In the medical treatment group, 10 of the 12 were also satisfied with the symptom relief while the other 2 did not improve significantly. Conclusions: Findings on SPECT-CT imaging appears to be easily explained the patients' pain. We recommended that SPECT/CT imaging was a feasible and useful clinical tool to improve diagnostic confidence or specificity when evaluating patients with FBSS.

Keywords: failed back surgery syndrome, oswestry disability index, SPECT-CT imaging, 99mTc-MDP, visual analogue scale

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576 Hybrid Nanostructures of Acrylonitrile Copolymers

Authors: A. Sezai Sarac

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Acrylonitrile (AN) copolymers with typical comonomers of vinyl acetate (VAc) or methyl acrylate (MA) exhibit better mechanical behaviors than its homopolymer. To increase processability of conjugated polymer, and to obtain a hybrid nano-structure multi-stepped emulsion polymerization was applied. Such products could be used in, i.e., drug-delivery systems, biosensors, gas-sensors, electronic compounds, etc. Incorporation of a number of flexible comonomers weakens the dipolar interactions among CN and thereby decreases melting point or increases decomposition temperatures of the PAN based copolymers. Hence, it is important to consider the effect of comonomer on the properties of PAN-based copolymers. Acrylonitrile vinylacetate (AN–VAc ) copolymers have the significant effect to their thermal behavior and are also of interest as precursors in the production of high strength carbon fibers. AN is copolymerized with one or two comonomers, particularly with vinyl acetate The copolymer of AN and VAc can be used either as a plastic (VAc > 15 wt %) or as microfibers (VAc < 15 wt %). AN provides the copolymer with good processability, electrochemical and thermal stability; VAc provides the mechanical stability. The free radical copolymerization of AN and VAc copolymer and core Shell structure of polyprrole composites,and nanofibers of poly(m-anthranilic acid)/polyacrylonitrile blends were recently studied. Free radical copolymerization of acrylonitrile (AN) – with different comonomers, i.e. acrylates, and styrene was realized using ammonium persulfate (APS) in the presence of a surfactant and in-situ polymerization of conjugated polymers was performed in this reaction medium to obtain core-shell nano particles. Nanofibers of such nanoparticles were obtained by electrospinning. Morphological properties of nanofibers are investigated by scanning electron microscopy (SEM) and atomic force spectroscopy (AFM). Nanofibers are characterized using Fourier Transform Infrared - Attenuated Total Reflectance spectrometer (FTIR-ATR), Nuclear Magnetic Resonance Spectroscopy (1H-NMR), differential scanning calorimeter (DSC), thermal gravimetric analysis (TGA), and Electrochemical Impedance Spectroscopy. The electrochemical Impedance results of the nanofibers were fitted to an equivalent curcuit by modelling (ECM).

Keywords: core shell nanoparticles, nanofibers, ascrylonitile copolymers, hybrid nanostructures

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575 A Study on Awareness and Attitude of First-Year Medical Students on Epilepsy in University of Khartoum 2020-2021

Authors: Mohammed E. Ibrahim, Baraa A. Taha, Kamil M. A. Shabban

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Background: Epilepsy is a common but widely misunderstood illness. Consequently, patients with epilepsy suffer from considerable stigmatization in society. This social stigma and discrimination often cause more suffering for the patients than the disease itself. Since very few studies have explored the misperceptions about epilepsy among university students in Sudan, it is not possible to provide focused intervention aimed at eliminating this discrimination. Methods: A cross-sectional study was applied among the first-year medical students at the University of Khartoum between December (2020) and February (2021). A 29-item standardized questionnaire was self-administered by 198 students (out of 320) who agreed to participate in this study. Google form was the tool used to collect the data. The data were analyzed using the Statistical Package for Social Science software version 26. Result: Overall, the results indicate a negative trend in knowledge and attitude toward epilepsy. The vast majority of the respondents (84.8%) have read or heard about epilepsy, while 43.9% had seen someone with epilepsy. Only 7.5% of the participants reported that epilepsy is contagious, whereas 43.4% of them think that epilepsy is a psychological disorder. About 62.2% of students think head/birth trauma is a cause of epilepsy. On the other side, about 15.7% and 5.1% believed that evil spirits and punishment from god can also be a possible cause of epilepsy; we found these false beliefs are more common in participants from rural areas (p-value < 0.05). In regard to attitude, 19.7% of students thought that it is inappropriate for a patient with epilepsy to have a child. This attitude correlates with the mother’s education as the percentage is higher for those who have lower mother’s education (through secondary school education and below) (p < 0.05). The majority of Our participant knew that some people with epilepsy need life-long drug treatment; this belief was found to be more common in females than their counterparts(p < 0.05). . Finally, most of the respondents (93.9%) thought that a child with epilepsy Can be successful in a normal class. This belief is four-time as common in participants whose mothers have higher education (through university education and above) compared with corresponding respondents (p < 0.05). Conclusion: This study concludes that students' knowledge about epilepsy is limited and requires immediate intervention through educational campaigns to develop a well-informed and tolerant community.

Keywords: epilepsy, awareness, attitude, university students, Sudan

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574 3D Microscopy, Image Processing, and Analysis of Lymphangiogenesis in Biological Models

Authors: Thomas Louis, Irina Primac, Florent Morfoisse, Tania Durre, Silvia Blacher, Agnes Noel

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In vitro and in vivo lymphangiogenesis assays are essential for the identification of potential lymphangiogenic agents and the screening of pharmacological inhibitors. In the present study, we analyse three biological models: in vitro lymphatic endothelial cell spheroids, in vivo ear sponge assay, and in vivo lymph node colonisation by tumour cells. These assays provide suitable 3D models to test pro- and anti-lymphangiogenic factors or drugs. 3D images were acquired by confocal laser scanning and light sheet fluorescence microscopy. Virtual scan microscopy followed by 3D reconstruction by image aligning methods was also used to obtain 3D images of whole large sponge and ganglion samples. 3D reconstruction, image segmentation, skeletonisation, and other image processing algorithms are described. Fixed and time-lapse imaging techniques are used to analyse lymphatic endothelial cell spheroids behaviour. The study of cell spatial distribution in spheroid models enables to detect interactions between cells and to identify invasion hierarchy and guidance patterns. Global measurements such as volume, length, and density of lymphatic vessels are measured in both in vivo models. Branching density and tortuosity evaluation are also proposed to determine structure complexity. Those properties combined with vessel spatial distribution are evaluated in order to determine lymphangiogenesis extent. Lymphatic endothelial cell invasion and lymphangiogenesis were evaluated under various experimental conditions. The comparison of these conditions enables to identify lymphangiogenic agents and to better comprehend their roles in the lymphangiogenesis process. The proposed methodology is validated by its application on the three presented models.

Keywords: 3D image segmentation, 3D image skeletonisation, cell invasion, confocal microscopy, ear sponges, light sheet microscopy, lymph nodes, lymphangiogenesis, spheroids

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573 The State of Research on Medicinal Plants in Morocco

Authors: Alami Ilyass, Loubna Kharchoufa, Elachouri Mostafa

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The two great realms of living diversity are cultural and biological. Today, both are being lost at an alarming rate. Of all the Earth’s biological diversity, plant kingdom is of high significance, and most essential to human welfare, in fact, medicinal plants are extensively exploited for countless purposes. Among these multiple uses, medicinal plants are the most important source of medicine for humankind healthcare and well being. In recent years there has been a great surge of public interest in the use of herbs and plants. Some scientists have viewed this phenomenon as a modern “herbal renaissance”. The importance of plants as medicines in developed and developing countries has recently been acknowledged by the United Nations (UN). However, to date fewer than 5% of the approximately 250,000 species of higher plants have been exhaustively studied for their potential pharmacological activity. A number of drugs from ethnobotanical leads have provided significant milestones in Western medicine. Despite this success, pharmacognosy research on Moroccan flora needs more studies aimed at the exploration of their therapeutic potential. A major weakness is the absence of strong funding agencies in the country, and a real national drug discovery program. Moreover, the lack of the coordination between different universities and research institutions leads, in most cases, to a waste of time, money and efforts of many researchers. In this work, we focus our attention on research into traditional indigenous medicinal plants in Morocco. Three parts constitute the head lines of this work: In the first one, we take up Moroccan biodiversity matter, the second part is devoted principally to the state of research into medicinal plants by Moroccan scholars and the last one is consecrated to the debate of factors which handicap the progress of research on phytomedicine in Morocco. The objectives of the present study are twofold: first, to highlight the state of the medicinal plants researches in Morocco. Second goal is to assess and correlate the levels of knowledge of the local flora to the research on medicinal plants to attempt to build capacity for research within Moroccan Scientific community at rate of developing country.

Keywords: Morocco, medicinal plants, ethnobotanical, pharmacognosy, phytomedicine

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572 3D Interpenetrated Network Based on 1,3-Benzenedicarboxylate and 1,2-Bis(4-Pyridyl) Ethane

Authors: Laura Bravo-García, Gotzone Barandika, Begoña Bazán, M. Karmele Urtiaga, Luis M. Lezama, María I. Arriortua

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Solid coordination networks (SCNs) are materials consisting of metal ions or clusters that are linked by polyfunctional organic ligands and can be designed to form tridimensional frameworks. Their structural features, as for example high surface areas, thermal stability, and in other cases large cavities, have opened a wide range of applications in fields like drug delivery, host-guest chemistry, biomedical imaging, chemical sensing, heterogeneous catalysis and others referred to greenhouse gases storage or even separation. In this sense, the use of polycarboxylate anions and dipyridyl ligands is an effective strategy to produce extended structures with the needed characteristics for these applications. In this context, a novel compound, [Cu4(m-BDC)4(bpa)2DMF]•DMF has been obtained by microwave synthesis, where m-BDC is 1,3-benzenedicarboxylate and bpa 1,2-bis(4-pyridyl)ethane. The crystal structure can be described as a three dimensional framework formed by two equal, interpenetrated networks. Each network consists of two different CuII dimers. Dimer 1 have two coppers with a square pyramidal coordination, and dimer 2 have one with a square pyramidal coordination and other with octahedral one, the last dimer is unique in literature. Therefore, the combination of both type of dimers is unprecedented. Thus, benzenedicarboxylate ligands form sinusoidal chains between the same type of dimers, and also connect both chains forming these layers in the (100) plane. These layers are connected along the [100] direction through the bpa ligand, giving rise to a 3D network with 10 Å2 voids in average. However, the fact that there are two interpenetrated networks results in a significant reduction of the available volume. Structural analysis was carried out by means of single crystal X-ray diffraction and IR spectroscopy. Thermal and magnetic properties have been measured by means of thermogravimetry (TG), X-ray thermodiffractometry (TDX), and electron paramagnetic resonance (EPR). Additionally, CO2 and CH4 high pressure adsorption measurements have been carried out for this compound.

Keywords: gas adsorption, interpenetrated networks, magnetic measurements, solid coordination network (SCN), thermal stability

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571 Deconstruction of the Term 'Shaman' in the Metaphorical Pair 'Artist as a Shaman'

Authors: Ilona Ivova Anachkova

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The analogy between the artist and the shaman as both being practitioners that more easily recognize and explore spiritual matters, and thus contribute to the society in a unique way has been implied in both Modernity and Postmodernity. The Romantic conception of the shaman as a great artist who helps common men see and understand messages of a higher consciousness has been employed throughout Modernity and is active even now. This paper deconstructs the term ‘shaman’ in the metaphorical analogy ‘artist – shaman’ that was developed more fully in Modernity in different artistic and scientific discourses. The shaman is a figure that to a certain extent adequately reflects the late modern and postmodern holistic views on the world. Such views aim at distancing from traditional religious and overly rationalistic discourses. However, the term ‘shaman’ can be well substituted by other concepts such as the priest, for example. The concept ‘shaman’ is based on modern ethnographic and historical investigations. Its later philosophical, psychological and artistic appropriations designate the role of the artist as a spiritual and cultural leader. However, the artist and the shaman are not fully interchangeable terms. The figure of the shaman in ‘primitive’ societies has performed many social functions that are now delegated to different institutions and positions. The shaman incorporates the functions of a judge, a healer. He is a link to divine entities. He is the creative, aspiring human being that has heightened sensitivity to the world in both its spiritual and material aspects. Building the metaphorical analogy between the shaman and the artist comes in many ways. Both are seen as healers of the society, having propensity towards connection to spiritual entities, or being more inclined to creativity than others. The ‘shaman’ however is a fashionable word for a spiritual person used perhaps because of the anti-traditionalist religious modern and postmodern views. The figure of the priest is associated with a too rational, theoretical and detached attitude towards spiritual matters, while the practices of the shaman and the artist are considered engaged with spirituality on a deeper existential level. The term ‘shaman’ however does not have priority of other words/figures that can explore and deploy spiritual aspects of reality. Having substituted the term ‘shaman’ in the pair ‘artist as a shaman’ with ‘the priest’ or literally ‘anybody,' we witness destruction of spiritual hierarchies and come to the view that everybody is responsible for their own spiritual and creative evolution.

Keywords: artist as a shaman, creativity, extended theory of art, functions of art, priest as an artist

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570 Effects of Pterostilbene in Brown Adipose Tissue from Obese Rats

Authors: Leixuri Aguirre, Iñaki Milton-Laskibar, Elizabeth Hijona, Luis Bujanda, Agnes M. Rimando, Maria P. Portillo

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Introduction: In recent years great attention has been paid by scientific community to phenolic compounds as active biomolecules naturally present in foodstuffs due to their beneficial effects on health. Pterostilbene is a resveratrol dimethylether derivative which shows higher biodisponibility. Objective. To analyze the effects of two doses of pterostilbene on several markers of thermogenic capacity in a model of genetic obesity, which shows reduced thermogenesis. Methods: The experiment was conducted with thirty Zucker (fa/fa) rats that were distributed in 3 experimental groups, the control group and two groups orally administered with pterostilbene at 15 and 30 mg/kg body weight/day for 6 weeks. Gene expression of Ucp1, Pgc-1α, Cpt1b, Pparα, Nfr1, Tfam and Cox-2 were assessed by RT-PCR, protein expression of UCP1 and GLUT4 by western blot and enzyme activity of carnitine palmitoyl transferase 1b and citrate synthase by spectrophotometry in interscapular brown adipose tissue (iBAT). Statistical analysis was performed by using one way ANOVA and Newman-Keuls as post-hoc test. Results: Pterostilbene did not change gene expression of Pgc-1α. However, significant increases were found in the expression of Ucp1, Pparα, Nfr-1 and Cox-2. Protein expression of UCP1 and GLUT4 was increased in animals treated with pterostilbene, as well as the activities of CPT-1b and CS. These effects were observed with both doses of pterostilbene, without differences between them. Conclusions: These results show that pterostilbene increases thermogenic and oxidative capacity of brown adipose tissue in obese rats. Whether these effects effectively contribute to the anti-obesity properties of these compound needs further research. Acknowledgments: MINECO-FEDER (AGL2015-65719-R), Basque Government (IT-572-13), University of the Basque Country (ELDUNANOTEK UFI11/32), Institut of Health Carlos III (CIBERobn). Iñaki Milton is a fellowship from the Basque Government.

Keywords: brown adipose tissue, pterostilbene, thermogenesis, uncoupling protein 1

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569 Dipeptide Functionalized Nanoporous Anodic Aluminium Oxide Membrane for Capturing Small Molecules

Authors: Abdul Mutalib Md Jani, Abdul Hadi Mahmud, Mohd Tajuddin Mohd Ali

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The rapid growth of interest in surface modification of nanostructures materials that exhibit improved structural and functional properties is attracting more researchers. The unique properties of highly ordered nanoporous anodic aluminium oxide (NAAO) membrane have been proposed as a platform for biosensing applications. They exhibit excellent physical and chemical properties with high porosity, high surface area, tunable pore sizes and excellent chemical resistance. In this study, NAAO was functionalized with 3-aminopropyltriethoxysilane (APTES) to prepared silane-modified NAAO. Amine functional groups are formed on the surface of NAAO during silanization and were characterized using Fourier Transform Infrared spectroscopy (FTIR). The synthesis of multi segment of peptide on NAAO surfaces can be realized by changing the surface chemistry of the NAAO membrane via click chemistry. By click reactions, utilizing alkyne terminated with amino group, various peptides tagged on NAAO can be envisioned from chiral natural or unnatural amino acids using standard coupling methods (HOBt, EDCI and HBTU). This strategy seemly versatile since coupling strategy of dipeptide with another amino acids, leading to tripeptide, tetrapeptide or pentapeptide, can be synthesized without purification. When an appropriate terminus is selected, multiple segments of amino acids can be successfully synthesized on the surfaces. The immobilized NAAO should be easily separated from the reaction medium by conventional filtration, thus avoiding complicated purification methods. Herein, we proposed to synthesize multi fragment peptide as a model for capturing and attaching various small biomolecules on NAAO surfaces and can be also applied as biosensing device, drug delivery systems and biocatalyst.

Keywords: nanoporous anodic aluminium oxide, silanization, peptide synthesise, click chemistry

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568 In-silico DFT Study, Molecular Docking, ADMET Predictions, and DMS of Isoxazolidine and Isoxazoline Analogs with Anticancer Properties

Authors: Moulay Driss Mellaoui, Khadija Zaki, Khalid Abbiche, Abdallah Imjjad, Rachid Boutiddar, Abdelouahid Sbai, Aaziz Jmiai, Souad El Issami, Al Mokhtar Lamsabhi, Hanane Zejli

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This study presents a comprehensive analysis of six isoxazolidine and isoxazoline derivatives, leveraging a multifaceted approach that combines Density Functional Theory (DFT), AdmetSAR analysis, and molecular docking simulations to explore their electronic, pharmacokinetic, and anticancer properties. Through DFT analysis, using the B3LYP-D3BJ functional and the 6-311++G(d,p) basis set, we optimized molecular geometries, analyzed vibrational frequencies, and mapped Molecular Electrostatic Potentials (MEP), identifying key sites for electrophilic attacks and hydrogen bonding. Frontier Molecular Orbital (FMO) analysis and Density of States (DOS) plots revealed varying stability levels among the compounds, with 1b, 2b, and 3b showing slightly higher stability. Chemical potential assessments indicated differences in binding affinities, suggesting stronger potential interactions for compounds 1b and 2b. AdmetSAR analysis predicted favorable human intestinal absorption (HIA) rates for all compounds, highlighting compound 3b superior oral effectiveness. Molecular docking and molecular dynamics simulations were conducted on isoxazolidine and 4-isoxazoline derivatives targeting the EGFR receptor (PDB: 1JU6). Molecular docking simulations confirmed the high affinity of these compounds towards the target protein 1JU6, particularly compound 3b, among the isoxazolidine derivatives, compound 3b exhibited the most favorable binding energy, with a g score of -8.50 kcal/mol. Molecular dynamics simulations over 100 nanoseconds demonstrated the stability and potential of compound 3b as a superior candidate for anticancer applications, further supported by structural analyses including RMSD, RMSF, Rg, and SASA values. This study underscores the promising role of compound 3b in anticancer treatments, providing a solid foundation for future drug development and optimization efforts.

Keywords: isoxazolines, DFT, molecular docking, molecular dynamic, ADMET, drugs.

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567 In vitro Modeling of Aniridia-Related Keratopathy by the Use of Crispr/Cas9 on Limbal Epithelial Cells and Rescue

Authors: Daniel Aberdam

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Haploinsufficiency of PAX6 in humans is the main cause of congenital aniridia, a rare eye disease characterized by reduced visual acuity. Patients have also progressive disorders including cataract, glaucoma and corneal abnormalities making their condition very challenging to manage. Aniridia-related keratopathy (ARK), caused by a combination of factors including limbal stem-cell deficiency, impaired healing response, abnormal differentiation, and infiltration of conjunctival cells onto the corneal surface, affects up to 95% of patients. It usually begins in the first decade of life resulting in recurrent corneal erosions, sub-epithelial fibrosis with corneal decompensation and opacification. Unfortunately, current treatment options for aniridia patients are currently limited. Although animal models partially recapitulate this disease, there is no in vitro cellular model of AKT needed for drug/therapeutic tools screening and validation. We used genome editing (CRISPR/Cas9 technology) to introduce a nonsense mutation found in patients into one allele of the PAX6 gene into limbal stem cells. Resulting mutated clones, expressing half of the amount of PAX6 protein and thus representative of haploinsufficiency were further characterized. Sequencing analysis showed that no off-target mutations were induced. The mutated cells displayed reduced cell proliferation and cell migration but enhanced cell adhesion. Known PAX6 targets expression was also reduced. Remarkably, addition of soluble recombinant PAX6 protein into the culture medium was sufficient to activate endogenous PAX6 gene and, as a consequence, rescue the phenotype. It strongly suggests that our in vitro model recapitulates well the epithelial defect and becomes a powerful tool to identify drugs that could rescue the corneal defect in patients. Furthermore, we demonstrate that the homeotic transcription factor Pax6 is able to be uptake naturally by recipient cells to function into the nucleus.

Keywords: Pax6, crispr/cas9, limbal stem cells, aniridia, gene therapy

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566 The Role of Criminal Law in Combating Transnational Organized Crime

Authors: Rizoyeva Marjona Rustam Qizi

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Transnational organized crime (TOC) represents one of the most significant threats to global security and social stability in the 21st century. Criminal networks operating across borders engage in activities such as drug trafficking, human trafficking, arms smuggling, and cybercrime, exploiting legal loopholes and jurisdictional challenges. In response, criminal law has evolved to address the complexities of TOC through enhanced international cooperation, harmonization of legal standards, and stronger enforcement mechanisms. This abstract explores the role of criminal law in combating TOC, focusing on three key areas: legislative frameworks, international collaboration, and enforcement practices. First, the development of international legal instruments such as the United Nations Convention against Transnational Organized Crime (UNTOC) has facilitated the standardization of legal definitions and procedures. Countries have adopted these frameworks to ensure a coordinated response to TOC, closing jurisdictional gaps and simplifying extradition processes. Second, international collaboration among law enforcement agencies, facilitated by organizations like INTERPOL and Europol, has enhanced information sharing and joint operations, making it more difficult for criminal organizations to evade detection. Finally, advancements in technology have improved investigative techniques, enabling law enforcement to track and dismantle criminal networks more effectively. However, despite these achievements, challenges remain. Issues such as corruption, insufficient resources, and differing legal systems continue to hinder the global fight against TOC. In conclusion, criminal law plays a pivotal role in the global effort to combat transnational organized crime by providing a legal framework for prosecution and fostering international cooperation. Ongoing reforms and technological innovations are essential for overcoming existing challenges and ensuring a more secure future. This abstract highlights the need for continuous adaptation of criminal law to address the evolving nature of TOC and underscores the importance of a unified international approach in achieving long-term success.

Keywords: transnational organized crime, criminal law, international cooperation, legal frameworks

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565 A Next Generation Multi-Scale Modeling Theatre for in silico Oncology

Authors: Safee Chaudhary, Mahnoor Naseer Gondal, Hira Anees Awan, Abdul Rehman, Ammar Arif, Risham Hussain, Huma Khawar, Zainab Arshad, Muhammad Faizyab Ali Chaudhary, Waleed Ahmed, Muhammad Umer Sultan, Bibi Amina, Salaar Khan, Muhammad Moaz Ahmad, Osama Shiraz Shah, Hadia Hameed, Muhammad Farooq Ahmad Butt, Muhammad Ahmad, Sameer Ahmed, Fayyaz Ahmed, Omer Ishaq, Waqar Nabi, Wim Vanderbauwhede, Bilal Wajid, Huma Shehwana, Muhammad Tariq, Amir Faisal

Abstract:

Cancer is a manifestation of multifactorial deregulations in biomolecular pathways. These deregulations arise from the complex multi-scale interplay between cellular and extracellular factors. Such multifactorial aberrations at gene, protein, and extracellular scales need to be investigated systematically towards decoding the underlying mechanisms and orchestrating therapeutic interventions for patient treatment. In this work, we propose ‘TISON’, a next-generation web-based multiscale modeling platform for clinical systems oncology. TISON’s unique modeling abstraction allows a seamless coupling of information from biomolecular networks, cell decision circuits, extra-cellular environments, and tissue geometries. The platform can undertake multiscale sensitivity analysis towards in silico biomarker identification and drug evaluation on cellular phenotypes in user-defined tissue geometries. Furthermore, integration of cancer expression databases such as The Cancer Genome Atlas (TCGA) and Human Proteome Atlas (HPA) facilitates in the development of personalized therapeutics. TISON is the next-evolution of multiscale cancer modeling and simulation platforms and provides a ‘zero-code’ model development, simulation, and analysis environment for application in clinical settings.

Keywords: systems oncology, cancer systems biology, cancer therapeutics, personalized therapeutics, cancer modelling

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564 D-Epi App: Mobile Application to Control Sodium Valproat Administration in Children with Idiopatic Epilepsy in Indonesia

Authors: Nyimas Annissa Mutiara Andini

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There are 325,000 children younger than age 15 in the U.S. have epilepsy. In Indonesia, 40% of 3,5 millions cases of epilepsy happens in children. The most common type of epilepsy, which affects 6 out of 10 people with the disorder, is called idiopathic epilepsy and which has no identifiable cause. One of the most commonly used medications in the treatment of this childhood epilepsy is sodium valproate. Administration of sodium valproat in children has a problem to fail. Nearly 60% of pediatric patients known were mildly, moderately, or severely non-adherent with therapy during the first six months of treatment. Many parents or caregiver took far less medication than prescribed, and the treatment-adherence pattern for the majority of patients was established during the first month of treatment. 42% of the patients were almost always given their medications as prescribed but 13% had very poor adherence even in the early weeks and months of treatment. About 7% of patients initially gave the medication correctly 90% of the time, but adherence dropped to around 20% within six months of starting treatment. Over the six months of observation, the total missing of administration is about four out of 14 doses in any given week. This fail can cause the epilepsy to relapse. Whereas, current reported epilepsy disorder were significantly more likely than those never diagnosed to experience depression (8% vs 2%), anxiety (17% vs 3%), attention-deficit/hyperactivity disorder (23% vs 6%), developmental delay (51% vs 3%), autism/autism spectrum disorder (16% vs 1%), and headaches (14% vs 5%) (all P< 0.05). They had a greater risk of limitation in the ability to do things (relative risk: 9.22; 95% CI: 7.56–11.24), repeating a school grade (relative risk: 2.59; CI: 1.52–4.40), and potentially having unmet medical and mental health needs. In the other side, technology can help to make our life easier. One of the technology, that we can use is a mobile application. A mobile app is a software program we can download and access directly using our phone. Indonesians are highly mobile centric. They use, on average, 6.7 applications over a 30 day period. This paper is aimed to describe an application that could help to control a sodium valproat administration in children; we call it as D-Epi app. D-Epi app is a downloadable application that can help parents or caregiver alert by a timer-related application to warn whether it is the time to administer the sodium valproat. It works not only as a standard alarm, but also inform important information about the drug and emergency stuffs to do to children with epilepsy. This application could help parents and caregiver to take care a child with epilepsy in Indonesia.

Keywords: application, children, D-Epi, epilepsy

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563 Optimization of Sucrose Concentration, PH Level and Inoculum Size for Callus Proliferation and Anti-bacterial Potential of Stevia Rebaudiana Bertoni

Authors: Inayat Ur Rahman Arshad

Abstract:

Stevia rebaudiana B. is a shrubby perennial herb of Asteraceae family that possesses the unique ability of accumulative non caloric sweet Steviol Glycosides (SGs). The purpose of the study is to optimize sugar concentration, pH level and inoculum size for inducing the callus with optimum growth and efficient antibacterial potential. Three different experiments were conducted in which Callus explant from three-months-old already established callus of Stevia reabudiana of four different sizes were inoculated on Murashige and Skoog (MS) basal medium supplemented with five different sucrose concentration and pH adjusted at four different levels. Maximum callus induction 100, 87.5 and 85.33% was resulted in the medium supplemented with 30g/l sucrose, pH maintained at 5.5 and inoculated with 1.25g inoculum respectively. Similarly, the highest fresh weight 65.00, 75.50 and 50.53g/l were noted in medium fortified with 40g/l sucrose, inoculated 1.25g inoculum and 6.0 pH level respectively. However, the callus developed in medium containing 50g/l sucrose found highly antibacterial potent with 27.3 and 26.5mm inhibition zone against P. vulgaris and B. subtilize respectively. Similarly, the callus grown on medium inoculated with 1.00g inoculum resulted in maximum antibacterial potential against S. aureus and P. vulgaris with 25 and 23.72mm inhibition zones respectively. However, in the case of pH levels the medium maintained at 6.5pH showed maximum antibacterial activity against P. vulgaris, B.subtilis and E.coli with 27.9, 25 and 23.72mm respectively. The ethyl acetate extract of Stevia callus and leaves did not show antibacterial potential against Xanthomonas campestris and Clavebactor michiganensis. In the entire experiment the standard antibacterial agent Streptomycin showed the highest inhibition zones from the rest of the callus extract, however the pure DMSO (Dimethyl Sulfoxide) caused no inhibitory zone against any bacteria. From these findings it is concluded that among various levels sucrose at the rate of 40g L-1, pH 6.0 and inoculums 0.75g was found best for most of the growth and quality attributes including fresh weight, dry weight and antibacterial activities and therefore can be recommended for callus proliferation and antibacterial potential of Stevia rebaudiana

Keywords: Steviol Glycosides, Skoog, Murashige, Clavebactor michiganensis

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562 Optimization of Sucrose Concentration, pH Level and Inoculum Size for Callus Proliferation and Anti-Bacterial Potential of Stevia rebaudiana Bertoni

Authors: Inayat Ur Rahman Arshad

Abstract:

Background: Stevia rebaudiana B. is a shrubby perennial herb of Asteraceae family that possesses the unique ability of accumulative non-caloric sweet steviol glycosides (SGs). Purpose: The purpose of the study is to optimize sugar concentration, pH level, and inoculum size for inducing the callus with optimum growth and efficient antibacterial potential. Method: Three different experiments were conducted in which Callus explant from three-months-old already established callus of Stevia reabudiana of four different sizes was inoculated on Murashige and Skoog (MS) basal medium supplemented with five different sucrose concentration and pH adjusted at four different levels. Results: Maximum callus induction 100, 87.5, and 85.33% resulted in the medium supplemented with 30 g/l sucrose, pH maintained at 5.5, and inoculated with 1.25g inoculum, respectively. Similarly, the highest fresh weights 65.00, 75.50, and 50.53 g/l were noted in a medium fortified with 40 g/l sucrose, inoculated 1.25g inoculum, and 6.0 pH level, respectively. However, the callus developed in a medium containing 50 g/l sucrose was found to be highly antibacterial potent with 27.3 and 26.5 mm inhibition zone against P. vulgaris and B. subtilis, respectively. Similarly, the callus grown on a medium inoculated with 1.00 g inoculum resulted in maximum antibacterial potential against S. aureus and P. vulgaris with 25 and 23.72 mm inhibition zone, respectively. However, in the case of pH levels, the medium maintained at 6.5 pH showed maximum antibacterial activity against P. vulgaris, B.subtilis, and E.coli with 27.9, 25, and 23.72 mm, respectively. The ethyl acetate extract of Stevia callus and leaves did not show antibacterial potential against Xanthomonas campestris and Clavebactor michiganensis. In the entire experiment, the standard antibacterial agent Streptomycin showed the highest inhibition zones among the rest of the callus extract; however, the pure dimethyl sulfoxide (DMSO) caused no inhibitory zone against any bacteria. Conclusion: From these findings, it is concluded that among various levels, sucrose @ 40 g L⁻¹, pH 6.0, and inoculums at 0.75 g were found best for most of the growth and quality attributes, including fresh weight, dry weight, and antibacterial activities and therefore can be recommended for callus proliferation and antibacterial potential of Stevia rebaudiana.

Keywords: Stevia rebaudiana, Steviol Glycosides, callus, Xanthomonas campestris

Procedia PDF Downloads 83