Search results for: lung toxicity
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1404

Search results for: lung toxicity

1134 Deposition of Size Segregated Particulate Matter in Human Respiratory Tract and Their Health Effects in Glass City Residents

Authors: Kalpana Rajouriya, Ajay Taneja

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Particulates are ubiquitous in the air environment and cause serious threats to human beings, such as lung cancer, COPD, and Asthma. Particulates mainly arise from industrial effluent, vehicular emission, and other anthropogenic activities. In the glass industrial city Firozabad, real-time monitoring of size segregated Particulate Matter (PM) and black carbon was done by Aerosol Black Carbon Detector (ABCD) and GRIMM portable aerosol Spectrometer at two different sites in which one site is urban and another is rural. The average mass concentration of size segregated PM during the study period (March & April 2022) was recorded as PM10 (223.73 g/m⁻³), PM5.0 (44.955 g/m⁻³), PM2.5 (59.275 g/m⁻³), PM1.0 (33.02 g/m⁻³), PM0.5 (2.05 g/m⁻³), and PM0.25 (2.99 g/m⁻³). The highest concentration of BC was found in Urban due to the emissions from diesel engines and wood burning, while NO2 was highest at the rural sites. The average concentrations of PM10 (6.08 and 2.73 times) PM2.5 exceeded the NAAQS and WHO guidelines. Particulate Matter deposition and health risk assessment was done by MPPD and USEPA model to know about the particulate matter toxicity in industrial residents. Health risk assessment results showed that Children are most likely to be affected by exposure of PM10 and PM2.5 and may have various non-carcinogenic and carcinogenic diseases. Deposition results inferred that the sensitive exposed population, especially 9 years old children, have high PM deposition as well as visualization and may be at risk of developing health-related problems from exposure to size-segregated PM. They will be discussed during presentation.

Keywords: particulate matter, black carbon, NO2, deposition of PM, health risk

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1133 Heavy Metal Concentrations in Sediments of Sta. Maria River, Laguna

Authors: Francis Angelo A. Sta. Ana

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Heavy metal pollutants are a major environmental concern in built-up areas in the Philippines. It causes negative effects on aquatic organisms and human health. Heavy metals concentrations of chromium, mercury, lead, copper, arsenic, zinc, cadmium, and nickel were investigated in Sta. Maria river, in Laguna. A total of 16 sediment samples were collected from the river at four stations. Atomic absorption spectroscopy (AAS) was used for element detection. It is found that copper is associated with chromium based on statistical analysis using principal component analysis (PCA). Conduct of Sediment Quality Guideline (SQG) revealed that chromium has high toxicity due to values higher than Sediment Quality Guidelines Probable Effect Level (SQG’s PEL). Copper, Nickel, and Pb fall on average toxicity while others are below PEL and effect range low (ERL).

Keywords: heavy metals, pollutants, sediment quality guidelines, atomic absorption spectroscopy

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1132 Comparison of Acetylcholinesterase Reactivators Cytotoxicity with Their Structure

Authors: Lubica Muckova, Petr Jost, Jaroslav Pejchal, Daniel Jun

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The development of acetylcholinesterase reactivators, i.e. antidotes against organophosphorus poisoning, is an important goal of defence research. The aim of this study was to compare cytotoxicity and chemical structure of 5 currently available (pralidoxime, trimedoxime, obidoxime, methoxime, and asoxime) and 4 newly developed compounds (K027, K074, K075, and K203). In oximes, there could be at least four important structural factors affecting their toxicity, including the number of oxime groups in the molecule, the position of oxime group(s) on pyridinium ring, the length of carbon linker, and the substitution by oxygen or insertion of the double bond into the connection chain. The cytotoxicity of tested substances was measured using colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay (MTT assay) in SH-SY5Y cell line. Toxicity was expressed as toxicological index IC₅₀. The tested compounds showed different cytotoxicity ranging from 1.5 to 27 mM. K027 was the least, and methoxime was the most toxic reactivator. The lowest toxicity was found in a monopyridinium reactivator and bispyridinium reactivators with simple 3C carbon linker. Shortening of connection chain length to 1C, incorporation of oxygen moiety into 3C compounds, elongation of carbon linker to 4C and insertion of a double bond into 4C substances increase AChE reactivators' cytotoxicity. Acknowledgements: This work was supported by a long-term organization development plan Medical Aspects of Weapons of Mass Destruction of the Faculty of Military Health Sciences, University of Defence.

Keywords: acetylcholinesterase, cytotoxicity, organophosphorus poisoning, reactivators of acetylcholinesterase

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1131 A Systems Approach to Targeting Cyclooxygenase: Genomics, Bioinformatics and Metabolomics Analysis of COX-1 -/- and COX-2-/- Lung Fibroblasts Providing Indication of Sterile Inflammation

Authors: Abul B. M. M. K. Islam, Mandar Dave, Roderick V. Jensen, Ashok R. Amin

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A systems approach was applied to characterize differentially expressed transcripts, bioinformatics pathways, and proteins and prostaglandins (PGs) from lung fibroblasts procured from wild-type (WT), COX-1-/- and COX-2-/- mice to understand system level control mechanism. Bioinformatics analysis of COX-2 and COX-1 ablated cells induced COX-1 and COX-2 specific signature respectively, which significantly overlapped with an 'IL-1β induced inflammatory signature'. This defined novel cross-talk signals that orchestrated coordinated activation of pathways of sterile inflammation sensed by cellular stress. The overlapping signals showed significant over-representation of shared pathways for interferon y and immune responses, T cell functions, NOD, and toll-like receptor signaling. Gene Ontology Biological Process (GOBP) and pathway enrichment analysis specifically showed an increase in mRNA expression associated with: (a) organ development and homeostasis in COX-1-/- cells and (b) oxidative stress and response, spliceosomes and proteasomes activity, mTOR and p53 signaling in COX-2-/- cells. COX-1 and COX-2 showed signs of functional pathways committed to cell cycle and DNA replication at the genomics level. As compared to WT, metabolomics analysis revealed a significant increase in COX-1 mRNA and synthesis of basal levels of eicosanoids (PGE2, PGD2, TXB2, LTB4, PGF1α, and PGF2α) in COX-2 ablated cells and increase in synthesis of PGE2, and PGF1α in COX-1 null cells. There was a compensation of PGE2 and PGF1α in COX-1-/- and COX-2-/- cells. Collectively, these results support a broader, differential and collaborative regulation of both COX-1 and COX-2 pathways at the metabolic, signaling, and genomics levels in cellular homeostasis and sterile inflammation induced by cellular stress.

Keywords: cyclooxygenases, inflammation, lung fibroblasts, systemic

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1130 Invasion of Pectinatella magnifica in Freshwater Resources of the Czech Republic

Authors: J. Pazourek, K. Šmejkal, P. Kollár, J. Rajchard, J. Šinko, Z. Balounová, E. Vlková, H. Salmonová

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Pectinatella magnifica (Leidy, 1851) is an invasive freshwater animal that lives in colonies. A colony of Pectinatella magnifica (a gelatinous blob) can be up to several feet in diameter large and under favorable conditions it exhibits an extreme growth rate. Recently European countries around rivers of Elbe, Oder, Danube, Rhine and Vltava have confirmed invasion of Pectinatella magnifica, including freshwater reservoirs in South Bohemia (Czech Republic). Our project (Czech Science Foundation, GAČR P503/12/0337) is focused onto biology and chemistry of Pectinatella magnifica. We monitor the organism occurrence in selected South Bohemia ponds and sandpits during the last years, collecting information about physical properties of surrounding water, and sampling the colonies for various analyses (classification, maps of secondary metabolites, toxicity tests). Because the gelatinous matrix is during the colony lifetime also a host for algae, bacteria and cyanobacteria (co-habitants), in this contribution, we also applied a high performance liquid chromatography (HPLC) method for determination of potentially present cyanobacterial toxins (microcystin-LR, microcystin-RR, nodularin). Results from the last 3-year monitoring show that these toxins are under limit of detection (LOD), so that they do not represent a danger yet. The final goal of our study is to assess toxicity risks related to fresh water resources invaded by Pectinatella magnifica, and to understand the process of invasion, which can enable to control it.

Keywords: cyanobacteria, fresh water resources, Pectinatella magnifica invasion, toxicity monitoring

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1129 An Ensemble Deep Learning Architecture for Imbalanced Classification of Thoracic Surgery Patients

Authors: Saba Ebrahimi, Saeed Ahmadian, Hedie Ashrafi

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Selecting appropriate patients for surgery is one of the main issues in thoracic surgery (TS). Both short-term and long-term risks and benefits of surgery must be considered in the patient selection criteria. There are some limitations in the existing datasets of TS patients because of missing values of attributes and imbalanced distribution of survival classes. In this study, a novel ensemble architecture of deep learning networks is proposed based on stacking different linear and non-linear layers to deal with imbalance datasets. The categorical and numerical features are split using different layers with ability to shrink the unnecessary features. Then, after extracting the insight from the raw features, a novel biased-kernel layer is applied to reinforce the gradient of the minority class and cause the network to be trained better comparing the current methods. Finally, the performance and advantages of our proposed model over the existing models are examined for predicting patient survival after thoracic surgery using a real-life clinical data for lung cancer patients.

Keywords: deep learning, ensemble models, imbalanced classification, lung cancer, TS patient selection

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1128 Genome-Wide Expression Profiling of Cicer arietinum Heavy Metal Toxicity

Authors: B. S. Yadav, A. Mani, S. Srivastava

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Chickpea (Cicer arietinum L.) is an annual, self-pollinating, diploid (2n = 2x = 16) pulse crop that ranks second in world legume production after common bean (Phaseolus vulgaris). ICC 4958 flowers approximately 39 days after sowing under peninsular Indian conditions and the crop matures in less than 90 days in rained environments. The estimated collective yield losses due to abiotic stresses (6.4 million t) have been significantly higher than for biotic stresses (4.8 million t). Most legumes are known to be salt sensitive, and therefore, it is becoming increasingly important to produce cultivars tolerant to high-salinity in addition to other abiotic and biotic stresses for sustainable chickpea production. Our aim was to identify the genes that are involved in the defence mechanism against heavy metal toxicity in chickpea and establish the biological network of heavy metal toxicity in chickpea. ICC4958 variety of chick pea was taken and grown in normal condition and 150µM concentration of different heavy metal salt like CdCl₂, K₂Cr2O₇, NaAsO₂. At 15th day leave samples were collected and stored in RNA Later solution microarray was performed for checking out differential gene expression pattern. Our studies revealed that 111 common genes that involved in defense mechanism were up regulated and 41 genes were commonly down regulated during treatment of 150µM concentration of CdCl₂, K₂Cr₂O₇, and NaAsO₂. Biological network study shows that the genes which are differentially expressed are highly connected and having high betweenness and centrality.

Keywords: abiotic stress, biological network, chickpea, microarray

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1127 Effects of Exhaust Gas Emitted by the Fleet on Public Health in the Region of Annaba (Algeria): Ecotoxicological Test on Durum Wheat (Triticum durum Desf.)

Authors: Aouissi Nora, Meksem Leila

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This work focused on the study of air pollution generated by the transport sector in the region of Annaba. Our study is based on two parts: the first one concerns an epidemiological investigation in the area of Annaba situated in the east Algerian coast, which deals with the development of the fleet and its impact on public health. To get a more precise idea of the impact of road traffic on public health, we consulted the computing center office of the National Social Insurance Fund. The information we were given by this office refers to the number of reported asthma and heart disease after medical examination during the period 2006-2010. The second part was devoted to the study of the toxicity of exhaust gases on some physical and biochemical parameters of durum wheat (Triticum durum Desf.). After germination and three-leaf stage, the pots are placed in a box of volume (0,096 m3) having an input which is linked directly to the exhaust pipe of a truck, and an outlet to prevent asphyxiation plant. The experience deals with 30 pots: 10 pots are exposed for 5 minutes to exhaust smoke; the other 10 are exposed for 15 minutes, and the remaining 10 for 30 minutes. The epidemiological study shows that the levels of pollutants emitted by the fleet are responsible for the increase of people respiratory and cardiovascular diseases. As for biochemical analyses of vegetation, they clearly show the toxicity of pollutants emitted by the exhaust gases, with an increase in total protein, proline and stimulation of detoxification enzyme (catalase).

Keywords: air pollution, toxicity, epidemiology, biochemistry

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1126 Cellular Mechanisms Involved in the Radiosensitization of Breast- and Lung Cancer Cells by Agents Targeting Microtubule Dynamics

Authors: Elsie M. Nolte, Annie M. Joubert, Roy Lakier, Maryke Etsebeth, Jolene M. Helena, Marcel Verwey, Laurence Lafanechere, Anne E. Theron

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Treatment regimens for breast- and lung cancers may include both radiation- and chemotherapy. Ideally, a pharmaceutical agent which selectively sensitizes cancer cells to gamma (γ)-radiation would allow administration of lower doses of each modality, yielding synergistic anti-cancer benefits and lower metastasis occurrence, in addition to decreasing the side-effect profiles. A range of 2-methoxyestradiol (2-ME) analogues, namely 2-ethyl-3-O-sulphamoyl-estra-1,3,5 (10) 15-tetraene-3-ol-17one (ESE-15-one), 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol) and 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16) were in silico-designed by our laboratory, with the aim of improving the parent compound’s bioavailability in vivo. The main effect of these compounds is the disruption of microtubule dynamics with a resultant mitotic accumulation and induction of programmed cell death in various cancer cell lines. This in vitro study aimed to determine the cellular responses involved in the radiation sensitization effects of these analogues at low doses in breast- and lung cancer cell lines. The oestrogen receptor positive MCF-7-, oestrogen receptor negative MDA-MB-231- and triple negative BT-20 breast cancer cell lines as well as the A549 lung cancer cell line were used. The minimal compound- and radiation doses able to induce apoptosis were determined using annexin-V and cell cycle progression markers. These doses (cell line dependent) were used to pre-sensitize the cancer cells 24 hours prior to 6 gray (Gy) radiation. Experiments were conducted on samples exposed to the individual- as well as the combination treatment conditions in order to determine whether the combination treatment yielded an additive cell death response. Morphological studies included light-, fluorescence- and transmission electron microscopy. Apoptosis induction was determined by flow cytometry employing annexin V, cell cycle analysis, B-cell lymphoma 2 (Bcl-2) signalling, as well as reactive oxygen species (ROS) production. Clonogenic studies were performed by allowing colony formation for 10 days post radiation. Deoxyribonucleic acid (DNA) damage was quantified via γ-H2AX foci and micronuclei quantification. Amplification of the p53 signalling pathway was determined by western blot. Results indicated that exposing breast- and lung cancer cells to nanomolar concentrations of these analogues 24 hours prior to γ-radiation induced more cell death than the compound- and radiation treatments alone. Hypercondensed chromatin, decreased cell density, a damaged cytoskeleton and an increase in apoptotic body formation were observed in cells exposed to the combination treatment condition. An increased number of cells present in the sub-G1 phase as well as increased annexin-V staining, elevation of ROS formation and decreased Bcl-2 signalling confirmed the additive effect of the combination treatment. In addition, colony formation decreased significantly. p53 signalling pathways were significantly amplified in cells exposed to the analogues 24 hours prior to radiation, as was the amount of DNA damage. In conclusion, our results indicated that pre-treatment of breast- and lung cancer cells with low doses of 2-ME analogues sensitized breast- and lung cancer cells to γ-radiation and induced apoptosis more so than the individual treatments alone. Future studies will focus on the effect of the combination treatment on non-malignant cellular counterparts.

Keywords: cancer, microtubule dynamics, radiation therapy, radiosensitization

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1125 Artificial Intelligence in Bioscience: The Next Frontier

Authors: Parthiban Srinivasan

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With recent advances in computational power and access to enough data in biosciences, artificial intelligence methods are increasingly being used in drug discovery research. These methods are essentially a series of advanced statistics based exercises that review the past to indicate the likely future. Our goal is to develop a model that accurately predicts biological activity and toxicity parameters for novel compounds. We have compiled a robust library of over 150,000 chemical compounds with different pharmacological properties from literature and public domain databases. The compounds are stored in simplified molecular-input line-entry system (SMILES), a commonly used text encoding for organic molecules. We utilize an automated process to generate an array of numerical descriptors (features) for each molecule. Redundant and irrelevant descriptors are eliminated iteratively. Our prediction engine is based on a portfolio of machine learning algorithms. We found Random Forest algorithm to be a better choice for this analysis. We captured non-linear relationship in the data and formed a prediction model with reasonable accuracy by averaging across a large number of randomized decision trees. Our next step is to apply deep neural network (DNN) algorithm to predict the biological activity and toxicity properties. We expect the DNN algorithm to give better results and improve the accuracy of the prediction. This presentation will review all these prominent machine learning and deep learning methods, our implementation protocols and discuss these techniques for their usefulness in biomedical and health informatics.

Keywords: deep learning, drug discovery, health informatics, machine learning, toxicity prediction

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1124 A Natural Killer T Cell Subset That Protects against Airway Hyperreactivity

Authors: Ya-Ting Chuang, Krystle Leung, Ya-Jen Chang, Rosemarie H. DeKruyff, Paul B. Savage, Richard Cruse, Christophe Benoit, Dirk Elewaut, Nicole Baumgarth, Dale T. Umetsu

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We examined characteristics of a Natural Killer T (NKT) cell subpopulation that developed during influenza infection in neonatal mice, and that suppressed the subsequent development of allergic asthma in a mouse model. This NKT cell subset expressed CD38 but not CD4, produced IFN-γ, but not IL-17, IL-4 or IL-13, and inhibited the development of airway hyperreactivity (AHR) through contact-dependent suppressive activity against helper CD4 T cells. The NKT subset expanded in the lungs of neonatal mice after infection with influenza, but also after treatment of neonatal mice with a Th1-biasing α-GalCer glycolipid analogue, Nu-α-GalCer. These results suggest that early/neonatal exposure to infection or to antigenic challenge can affect subsequent lung immunity by altering the profile of cells residing in the lung and that some subsets of NKT cells can have direct inhibitory activity against CD4+ T cells in allergic asthma. Importantly, our results also suggest a potential therapy for young children that might provide protection against the development of asthma.

Keywords: NKT subset, asthma, airway hyperreactivity, hygiene hypothesis, influenza

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1123 Valorization of Lignocellulosic Wastes– Evaluation of Its Toxicity When Used in Adsorption Systems

Authors: Isabel Brás, Artur Figueirinha, Bruno Esteves, Luísa P. Cruz-Lopes

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The agriculture lignocellulosic by-products are receiving increased attention, namely in the search for filter materials that retain contaminants from water. These by-products, specifically almond and hazelnut shells are abundant in Portugal once almond and hazelnuts production is a local important activity. Hazelnut and almond shells have as main constituents lignin, cellulose and hemicelluloses, water soluble extractives and tannins. Along the adsorption of heavy metals from contaminated waters, water soluble compounds can leach from shells and have a negative impact in the environment. Usually, the chemical characterization of treated water by itself may not show environmental impact caused by the discharges when parameters obey to legal quality standards for water. Only biological systems can detect the toxic effects of the water constituents. Therefore, the evaluation of toxicity by biological tests is very important when deciding the suitability for safe water discharge or for irrigation applications. The main purpose of the present work was to assess the potential impacts of waters after been treated for heavy metal removal by hazelnut and almond shells adsorption systems, with short term acute toxicity tests. To conduct the study, water at pH 6 with 25 mg.L-1 of lead, was treated with 10 g of shell per litre of wastewater, for 24 hours. This procedure was followed for each bark. Afterwards the water was collected for toxicological assays; namely bacterial resistance, seed germination, Lemna minor L. test and plant grow. The effect in isolated bacteria strains was determined by disc diffusion method and the germination index of seed was evaluated using lettuce, with temperature and humidity germination control for 7 days. For aquatic higher organism, Lemnas were used with 4 days contact time with shell solutions, in controlled light and temperature. For terrestrial higher plants, biomass production was evaluated after 14 days of tomato germination had occurred in soil, with controlled humidity, light and temperature. Toxicity tests of water treated with shells revealed in some extent effects in the tested organisms, with the test assays showing a close behaviour as the control, leading to the conclusion that its further utilization may not be considered to create a serious risk to the environment.

Keywords: lignocellulosic wastes, adsorption, acute toxicity tests, risk assessment

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1122 Polysulfide as Active ‘Stealth’ Polymers with Additional Anti-Inflammatory Activity

Authors: Farah El Mohtadi, Richard d'Arcy, Nicola Tirelli

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Since 40 years, poly (ethylene glycol) (PEG) has been the gold standard in biomaterials and drug delivery, because of its combination of chemical and biological inertness. However, the possibility of its breakdown under oxidative conditions and the demonstrated development of anti-PEG antibodies highlight the necessity to develop carriers based on materials with increased stability in a challenging biological environment. Here, we describe the synthesis of polysulfide via anionic ring-opening polymerization. In vitro, the synthesized polymer was characterized by low toxicity and a level of complement activation (in human plasma) and macrophage uptake slightly lower than PEG and poly (2‐methyl-2‐oxazoline) (PMOX), of a similar size. Importantly, and differently from PEG, on activated macrophages, the synthesized polymer showed a strong and dose-dependent ROS scavenging activity, which resulted in the corresponding reduction of cytokine production. Therefore, the results from these studies show that polysulfide is highly biocompatible and are potential candidates to be used as an alternative to PEG for various applications in nanomedicine.

Keywords: PEG, low toxicity, ROS scavenging, biocompatible

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1121 Visualizing Imaging Pathways after Anatomy-Specific Follow-Up Imaging Recommendations

Authors: Thusitha Mabotuwana, Christopher S. Hall

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Radiologists routinely make follow-up imaging recommendations, usually based on established clinical practice guidelines, such as the Fleischner Society guidelines for managing lung nodules. In order to ensure optimal care, it is important to make guideline-compliant recommendations, and also for patients to follow-up on these imaging recommendations in a timely manner. However, determining such compliance rates after a specific finding has been observed usually requires many time-consuming manual steps. To address some of these limitations with current approaches, in this paper we discuss a methodology to automatically detect finding-specific follow-up recommendations from radiology reports and create a visualization for relevant subsequent exams showing the modality transitions. Nearly 5% of patients who had a lung related follow-up recommendation continued to have at least eight subsequent outpatient CT exams during a seven year period following the recommendation. Radiologist and section chiefs can use the proposed tool to better understand how a specific patient population is being managed, identify possible deviations from established guideline recommendations and have a patient-specific graphical representation of the imaging pathways for an abstract view of the overall treatment path thus far.

Keywords: follow-up recommendations, follow-up tracking, care pathways, imaging pathway visualization

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1120 Down Regulation of Smad-2 Transcription and TGF-B1 Signaling in Nano Sized Titanium Dioxide-Induced Liver Injury in Mice by Potent Antioxidants

Authors: Maha Z. Rizk, Sami A. Fattah, Heba M. Darwish, Sanaa A. Ali, Mai O. Kadry

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Although it is known that nano-TiO2 and other nanoparticles can induce liver toxicity, the mechanisms and the molecular pathogenesis are still unclear. The present study investigated some biochemical indices of nano-sized Titanium dioxide (TiO2 NPS) toxicity in mice liver and the ameliorative efficacy of individual and combined doses of idebenone, carnosine and vitamin E. Nano-anatase TiO2 (21 nm) was administered as a total oral dose of 2.2 gm/Kg daily for 2 weeks followed by the afore-mentioned antioxidants daily either individually or in combination for 1month. TiO2-NPS induced a significant elevation in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatic oxidative stress biomarkers [lipid peroxides (LP), and nitric oxide levels (NOX), while it significantly reduced glutathione reductase (GR), reduced glutathione (GSH) and glutathione peroxidase(GPX) levels. Moreover the quantitative RT-PCR analysis showed that nano-anatase TiO2 can significantly alter the mRNA and protein expressions of the fibrotic factors TGF-B1, VEGFand Smad-2. Histopathological examination of hepatic tissue reinforced the previous biochemical results. Our results also implied that inflammatory responses and liver injury may be involved in nano-anatase TiO2-induced liver toxicity Tumor necrosis factor-α (TNF-α) and Interleukin -6 (IL-6) and increased the percent of DNA damage which was assessed by COMET assay in addition to the apoptotic marker Caspase-3. Moreover mRNA gene expression observed by RT-PCR showed a significant overexpression in nuclear factor relation -2 (Nrf2), nuclear factor kappa beta (NF-Kβ) and the apoptotic factor (bax), and a significant down regulation in the antiapoptotic factor (bcl2) level. In conclusion idebenone, carnosine and vitamin E ameliorated the deviated previously mentioned parameters with variable degrees with the most pronounced role in alleviating the hazardous effect of TiO2 NPS toxicity following the combination regimen.

Keywords: Nano-anatase TiO2, TGF-B1, SMAD-2

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1119 Impact of UV on Toxicity of Zn²⁺ and ZnO Nanoparticles to Lemna minor

Authors: Gabriela Kalcikova, Gregor Marolt, Anita Jemec Kokalj, Andreja Zgajnar Gotvajn

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Since the 90’s, nanotechnology is one of the fastest growing fields of science. Nanomaterials are increasingly becoming part of many products and technologies. Metal oxide nanoparticles are among the most used nanomaterials. Zinc oxide nanoparticles (nZnO) is widely used due to its versatile properties; it has been used in products including plastics, paints, food, batteries, solar cells and cosmetic products. It is also a very effective photocatalyst used for water treatment. Such expanding application of nZnO increases their possible occurrence in the environment. In the aquatic ecosystem nZnO interact with natural environmental factors such as UV radiation, and thus it is essential to evaluate possible interaction between them. In this context, the aim of our study was to evaluate combined ecotoxicity of nZnO and Zn²⁺ on duckweed Lemna minor in presence or absence UV. Inhibition of vegetative growth of duckweed Lemna minor was monitored over a period of 7 days in multi-well plates. After the experiment, specific growth rate was determined. ZnO nanoparticles used were of primary size 13.6 ± 1.7 nm. The test was conducted with nominal nZnO and Zn²⁺ (in form of ZnCl₂) concentrations of 1, 10, 100 mg/L. Experiment was repeated with presence of natural intensity of UV (8h UV, 10 W/m² UVA, 0.5 W/m² UVB). Concentration of Zn during the test was determined by ICP-MS. In the regular experiment (absence of UV) the specific growth rate was slightly increased by low concentrations of nZnO and Zn²⁺ in comparison to control. However, 10 and 100 mg/L of Zn²⁺ resulted in 45% and 68% inhibition of the specific growth rate, respectively. In case of nZnO both concentrations (10 and 100 mg/L) resulted in similar ~ 30% inhibition and the response was not dose-dependent. The lack of the dose-response relationship is often observed in case of nanoparticles. The possible explanation is that the physical impact prevails instead of chemical ones. In the presence of UV the toxicity of Zn²⁺ was increased and 100 mg/L of Zn²⁺ caused total inhibition of the specific growth rate (100%). On the other hand, 100 mg/L of nZnO resulted in low inhibition (19%) in comparison to the experiment without UV (30%). It is thus expected, that tested nZnO is low photoactive, but could have a good UV absorption and/or reflective properties and thus protect duckweed against UV impacts. Measured concentration of Zn in the test suspension decreased only about 4% after 168h in the case of ZnCl₂. On the other hand concentration of Zn in nZnO test decreased by 80%. It is expected that nZnO were partially dissolved in the medium and at the same time agglomeration and sedimentation of particles took place and thus the concentration of Zn at the water level decreased. Results of our study indicated, that nZnO combined with UV of natural intensity does not increase toxicity of nZnO, but slightly protect the plant against UV negative effects. When Zn²⁺ and ZnO results are compared it seems that dissolved Zn plays a central role in the nZnO toxicity.

Keywords: duckweed, environmental factors, nanoparticles, toxicity

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1118 Nephrotoxicity and Hepatotoxicity Induced by Chronic Aluminium Exposure in Rats: Impact of Nutrients Combination versus Social Isolation and Protein Malnutrition

Authors: Azza A. Ali, Doaa M. Abd El-Latif, Amany M. Gad, Yasser M. A. Elnahas, Karema Abu-Elfotuh

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Background: Exposure to Aluminium (Al) has been increased recently. It is found in food products, food additives, drinking water, cosmetics and medicines. Chronic consumption of Al causes oxidative stress and has been implicated in several chronic disorders. Liver is considered as the major site for detoxification while kidney is involved in the elimination of toxic substances and is a target organ of metal toxicity. Social isolation (SI) or protein malnutrition (PM) also causes oxidative stress and has negative impact on Al-induced nephrotoxicity as well as hepatotoxicity. Coenzyme Q10 (CoQ10) is a powerful intracellular antioxidant with mitochondrial membrane stabilizing ability while wheat grass is a natural product with antioxidant, anti-inflammatory and different protective activities, cocoa is also potent antioxidants and can protect against many diseases. They provide different degrees of protection from the impact of oxidative stress. Objective: To study the impact of social isolation together with Protein malnutrition on nephro- and hepato-toxicity induced by chronic Al exposure in rats as well as to investigate the postulated protection using a combination of Co Q10, wheat grass and cocoa. Methods: Eight groups of rats were used; four served as protected groups and four as un-protected. Each of them received daily for five weeks AlCl3 (70 mg/kg, IP) for Al-toxicity model groups except one group served as control. Al-toxicity model groups were divided to Al-toxicity alone, SI- associated PM (10% casein diet) and Al- associated SI&PM groups. Protection was induced by oral co-administration of CoQ10 (200mg/kg), wheat grass (100mg/kg) and cocoa powder (24mg/kg) combination together with Al. Biochemical changes in total bilirubin, lipids, cholesterol, triglycerides, glucose, proteins, creatinine and urea as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate deshydrogenase (LDH) were measured in serum of all groups. Specimens of kidney and liver were used for assessment of oxidative parameters (MDA, SOD, TAC, NO), inflammatory mediators (TNF-α, IL-6β, nuclear factor kappa B (NF-κB), Caspase-3) and DNA fragmentation in addition to evaluation of histopathological changes. Results: SI together with PM severely enhanced nephro- and hepato-toxicity induced by chronic Al exposure. Co Q10, wheat grass and cocoa combination showed clear protection against hazards of Al exposure either alone or when associated with SI&PM. Their protection were indicated by the significant decrease in Al-induced elevations in total bilirubin, lipids, cholesterol, triglycerides, glucose, creatinine and urea levels as well as ALT, AST, ALP, LDH. Liver and kidney of the treated groups also showed significant decrease in MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3 and DNA fragmentation, together with significant increase in total proteins, SOD and TAC. Biochemical results were confirmed by the histopathological examinations. Conclusion: SI together with PM represents a risk factor in enhancing nephro- and hepato-toxicity induced by Al in rats. CoQ10, wheat grass and cocoa combination provide clear protection against nephro- and hepatotoxicity as well as the consequent degenerations induced by chronic Al-exposure even when associated with the risk of SI together with PM.

Keywords: aluminum, nephrotoxicity, hepatotoxicity, isolation and protein malnutrition, coenzyme Q10, wheatgrass, cocoa, nutrients combinations

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1117 Toxicity and Biodegradability of Veterinary Antibiotic Tiamulin

Authors: Gabriela Kalcikova, Igor Bosevski, Ula Rozman, Andreja Zgajnar Gotvajn

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Antibiotics are extensively used in human medicine and also in animal husbandry to prevent or control infections. Recently, a lot of attention has been put on veterinary antibiotics, because their global consumption is increasing and it is expected to be 106.600 tons in 2030. Most of veterinary antibiotics are introduced into the environment via animal manure, which is used as fertilizer. One of such veterinary antibiotics is tiamulin. It is used the form of fumarate for treatment of pig and poultry. It is used against prophylaxis of dysentery, pneumonia and mycroplasmal infections, but its environmental impact is practically unknown. Tiamulin has been found very persistent in animal manure and thus it is expected that can be, during rainfalls, transported into the aquatic environment and affect various organisms. For assessment of its environmental impact, it is necessary to evaluate its biodegradability and toxicity to various organisms from different levels of a food chain. Therefore, the aim of our study was to evaluate ready biodegradability and toxicity of tiamulin fumarate to various organisms. Bioassay used included luminescent bacterium Vibrio fischeri heterotrophic and nitrifying microorganisms of activated sludge, water flea Daphnia magna and duckweed Lemna minor. For each species, EC₅₀ values were calculated. Biodegradability test was used for determination of ready biodegradability and it provides information about biodegradability of tiamulin under the most common environmental conditions. Results of our study showed that tiamulin differently affects selected organisms. The most sensitive organisms were water fleas with 48hEC₅₀ = 14.2 ± 4.8 mg/L and duckweed with 168hEC₅₀ = 22.6 ± 0.8 mg/L. Higher concentrations of tiamulin (from 10 mg/L) significantly affected photosynthetic pigments content in duckweed and concentrations above 80 mg/L cause visible chlorosis. It is in agreement with previous studies showing significant effect of tiamulin on green algae and cyanobacteria. Tiamuline has a low effect on microorganisms. The lower toxicity was observed for heterotrophic microorganisms (30minEC₅₀ = 1656 ± 296 mg/L), than Vibrio fisheri (30minEC₅₀ = 492 ± 21) and the most sensitive organisms were nitrifying microorganisms (30minEC₅₀ = 183 ± 127 mg/L). The reason is most probably the mode of action of tiamulin being effective to gram-positive bacteria while gram-negative (e.g., Vibrio fisheri) are more tolerant to tiamulin. Biodegradation of tiamulin was very slow with a long lag-phase being 20 days. The maximal degradation reached 40 ± 2 % in 43 days of the test and tiamulin as other antibiotics (e.g. ciprofloxacin) are not easily biodegradable. Tiamulin is widely used antibiotic in veterinary medicine and thus present in the environment. According to our results, tiamulin can have negative effect on water fleas and duckweeds, but the concentrations are several magnitudes higher than that found in any environmental compartment. Tiamulin is low toxic to tested microorganisms, but it is very low biodegradable and thus possibly persistent in the environment.

Keywords: antibiotics, biodegradability, tiamulin, toxicity

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1116 The Impact of COVID-19 Waste on Aquatic Organisms: Nano/microplastics and Molnupiravir in Salmo trutta Embryos and Lervae

Authors: Živilė Jurgelėnė, Vitalijus Karabanovas, Augustas Morkvėnas, Reda Dzingelevičienė, Nerijus Dzingelevičius, Saulius Raugelė, Boguslaw Buszewski

Abstract:

The short- and long-term effects of COVID-19 antiviral drug molnupiravir and micro/nanoplastics on the early development of Salmo trutta were investigated using accumulation and exposure studies. Salmo trutta were used as standardized test organisms in toxicity studies of COVID-19 waste contaminants. The 2D/3D imaging was performed using confocal fluorescence spectral imaging microscopy to assess the uptake, bioaccumulation, and distribution of molnupiravir and micro/nanoplastics complex in live fish. Our study results demonstrated that molnupiravir may interact with a micro/nanoplastics and modify their spectroscopic parameters and toxicity to S. trutta embryos and larvae. The 0.2 µm size microplastics at a concentration of 10 mg/L were found to be stable in aqueous media than 0.02 µm, and 2 µm sizes polymeric particles. This study demonstrated that polymeric particles can adsorb molnupiravir that are present in mixtures and modify the accumulation of molnupiravir in Salmo trutta embryos and larvae. In addition, 2D/3D confocal fluorescence imaging showed that the single polymeric particle hardly accumulates and couldn't penetrate outer tissues of the tested organism. However, co-exposure micro/nanoplastics and molnupiravir could significantly enhance the polymeric particles capability of accumulating on surface tissues and penetrating surface tissue of fish in early development. Exposure to molnupiravir at 2 g/L concentration and co-exposure to micro/nanoplastics and molnupiravir did not bring about survival changes in in the early stages of Salmo trutta development, but we observed the reduction in heart rate and decrease in gill ventilation. The statistical analysis confirmed that micro/nanoplastics used in combination with molnupiravir enhance the toxicity of the latter micro/nanoplastics to embryos and larvae. This research has received funding from the European Regional Development Fund (project No 13.1.1-LMT-K-718-05-0014) under a grant agreement with the Research Council of Lithuania (LMTLT), and it was funded as part of the European Union’s measure in response to the COVID-19 pandemic.

Keywords: fish, micro/nanoplastics, molnupiravir, toxicity

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1115 Heterogeneous Photocatalytic Degradation of Ibuprofen in Ultrapure Water, Municipal and Pharmaceutical Industry Wastewaters Using a TiO2/UV-LED System

Authors: Nabil Jallouli, Luisa M. Pastrana-Martínez, Ana R. Ribeiro, Nuno F. F. Moreira, Joaquim L. Faria, Olfa Hentati, Adrián M. T. Silva, Mohamed Ksibi

Abstract:

Degradation and mineralization of ibuprofen (IBU) were investigated using Ultraviolet (UV) Light Emitting Diodes (LEDs) in TiO2 photocatalysis. Samples of ultrapure water (UP) and a secondary treated effluent of a municipal wastewater treatment plant (WWTP), both spiked with IBU, as well as a highly concentrated IBU (230 mgL-1) pharmaceutical industry wastewater (PIWW), were tested in the TiO2/UV-LED system. Three operating parameters, namely, pH, catalyst load and number of LEDs were optimized. The process efficiency was evaluated in terms of IBU removal using high performance liquid chromatography (HPLC) and ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). Additionally, the mineralization was investigated by determining the dissolved organic carbon (DOC) content. The chemical structures of transformation products were proposed based on the data obtained using liquid chromatography with a high resolution mass spectrometer ion trap/time-of-flight (LC-MS-IT-TOF). A possible pathway of IBU degradation was accordingly proposed. Bioassays were performed using the marine bacterium Vibrio fischeri to evaluate the potential acute toxicity of original and treated wastewaters. TiO2 heterogeneous photocatalysis was efficient to remove IBU from UP and from PIWW, and less efficient in treating the wastewater from the municipal WWTP. The acute toxicity decreased by ca. 40% after treatment, regardless of the studied matrix.

Keywords: acute toxicity, Ibuprofen, UV-LEDs, wastewaters

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1114 Dental Fluorosis in Domestic Animals Inhabiting Industrial Area of Udaipur, Rajasthan, India

Authors: Lalita Panchal, Zulfiya Sheikh

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Fluoride is essential for teeth and bones development not only for human beings but also for animals. But excess intake of fluoride causes harmful effects on health. Fluorosis is a worldwide health hazard and India is also one of the endemic countries. Udaipur district of Rajasthan is also prone to fluorosis and superphosphate industries are aggravating fluoride toxicity in this area. Grazing fields for animals in the close vicinity of the industries, fodder and water are fluoride contaminated. Fluoride toxicity in the form of dental fluorosis was observed in domestic animals, inhabiting industrial area near Udaipur, where superphosphate fertilizer plants are functioning and releasing fluoride and fumes and effluents into the surroundings. These fumes and gases directly affect the vegetation of grazing field, thus allowing entry of fluoride into the food chain. A survey was conducted in this area to assess the severity of fluorosis, in 2015-16. It was a house to house survey and animal owners were asked for their fodder and water supply. Anterior teeth of the animal were observed. Domestic animals exhibited mild to severe signs of dental fluorosis. Teeth showed deep brown staining, patches, lines and abrasions. Even immature animals were affected badly. Most of the domestic animals were affected, but goats of this area showed chronic symptoms of fluorosis. Due to abrasion of teeth and paining teeth their chewing or grazing capacity and appetite reduced. Eventually, it reduced the life span of animals and increased the mortality rate.

Keywords: domestic animals, fluoride toxicity, industrial fluorosis, superphosphate fertilizers

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1113 Cylindrical Spacer Shape Optimization for Enhanced Inhalation Therapy

Authors: Shahab Azimi, Siamak Arzanpour, Anahita Sayyar

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Asthma and Chronic obstructive pulmonary disease (COPD) are common lung diseases that have a significant global impact. Pressurized metered dose inhalers (pMDIs) are widely used for treatment, but they can have limitations such as high medication release speed resulting in drug deposition in the mouth or oral cavity and difficulty achieving proper synchronization with inhalation by users. Spacers are add-on devices that improve the efficiency of pMDIs by reducing the release speed and providing space for aerosol particle breakup to have finer and medically effective medication. The aim of this study is to optimize the size and cylindrical shape of spacers to enhance their drug delivery performance. The study was based on fluid dynamics theory and employed Ansys software for simulation and optimization. Results showed that optimization of the spacer's geometry greatly influenced its performance and improved drug delivery. This study provides a foundation for future research on enhancing the efficiency of inhalation therapy for lung diseases.

Keywords: asthma, COPD, pressurized metered dose inhalers, spacers, CFD, shape optimization

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1112 Effect of Chronic Exposure to Diazinon on Glucose Homeostasis and Oxidative Stress in Pancreas of Rats and the Potential Role of Mesna in Ameliorating This Effect

Authors: Azza El-Medany, Jamila El-Medany

Abstract:

Residential and agricultural pesticide use is widespread in the world. Their extensive and indiscriminative use, in addition with their ability to interact with biological systems other than their primary targets constitute a health hazards to both humans and animals. The toxic effects of pesticides include alterations in metabolism; there is a lack of knowledge that organophosphates can cause pancreatic toxicity. The primary goal of this work is to study the effects of chronic exposure to Diazinon an organophosphate used in agriculture on pancreatic tissues and evaluate the ameliorating effect of Mesna as antioxidant on the toxicity of Diazinon on pancreatic tissues.40 adult male rats, their weight ranged between 300-350 g. The rats were classified into three groups; control (10 rats) was received corn oil at a dose of 1 0 mg/kg/day by gavage once a day for 2 months. Diazinon (15 rats) was received Diazinon at a dose of 10 mg/kg/day dissolved in corn oil by gavage once a day for 2 months. Treated group (15 rats), were received Mesna 180mg/kg once a week by gavage 15 minutes before administration of Diazinon for 2 months. At the end of the experiment, animals were anesthetized, blood samples were taken by cardiac puncture for glucose and insulin assays and pancreas was removed and divided into 3 portions; first portion for histopathological study; second portion for ultrastructural study; third portion for biochemical study using Elisa Kits including determination of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), myeloperoxidase activity (MPO), interleukin 1β (IL-1β). A significant increase in the levels of MDA, TNF-α, MPO activity, IL-1β, serum glucose levels in the toxicated group with Diazinon were observed, while a significant reduction was noticed in GSH in serum insulin levels. After treatment with Mesna a significant reduction was observed in the previously mentioned parameters except that there was a significant rise in GSH in insulin levels. Histopathological and ultra-structural studies showed destruction in pancreatic tissues and β cells were the most affected cells among the injured islets as compared with the control group. The current study try to spot light about the effects of chronic exposure to pesticides on vital organs as pancreas also the role of oxidative stress that may be induced by them in evoking their toxicity. This study shows the role of antioxidant drugs in ameliorating or preventing the toxicity. This appears to be a promising approach that may be considered as a complementary treatment of pesticide toxicity.

Keywords: Diazinon, reduced glutathione, myeloperoxidase activity, tumor necrosis factor α, Mesna

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1111 Monitoring Air Pollution Effects on Children for Supporting Public Health Policy: Preliminary Results of MAPEC_LIFE Project

Authors: Elisabetta Ceretti, Silvia Bonizzoni, Alberto Bonetti, Milena Villarini, Marco Verani, Maria Antonella De Donno, Sara Bonetta, Umberto Gelatti

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Introduction: Air pollution is a global problem. In 2013, the International Agency for Research on Cancer (IARC) classified air pollution and particulate matter as carcinogenic to human. The study of the health effects of air pollution in children is very important because they are a high-risk group in terms of the health effects of air pollution and early exposure during childhood can increase the risk of developing chronic diseases in adulthood. The MAPEC_LIFE (Monitoring Air Pollution Effects on Children for supporting public health policy) is a project founded by EU Life+ Programme which intends to evaluate the associations between air pollution and early biological effects in children and to propose a model for estimating the global risk of early biological effects due to air pollutants and other factors in children. Methods: The study was carried out on 6-8-year-old children living in five Italian towns in two different seasons. Two biomarkers of early biological effects, primary DNA damage detected with the comet assay and frequency of micronuclei, were investigated in buccal cells of children. Details of children diseases, socio-economic status, exposures to other pollutants and life-style were collected using a questionnaire administered to children’s parents. Child exposure to urban air pollution was assessed by analysing PM0.5 samples collected in the school areas for PAHs and nitro-PAHs concentration, lung toxicity and in vitro genotoxicity on bacterial and human cells. Data on the chemical features of the urban air during the study period were obtained from the Regional Agency for Environmental Protection. The project created also the opportunity to approach the issue of air pollution with the children, trying to raise their awareness on air quality, its health effects and some healthy behaviors by means of an educational intervention in the schools. Results: 1315 children were recruited for the study and participate in the first sampling campaign in the five towns. The second campaign, on the same children, is still ongoing. The preliminary results of the tests on buccal mucosa cells of children will be presented during the conference as well as the preliminary data about the chemical composition and the toxicity and genotoxicity features of PM0.5 samples. The educational package was tested on 250 children of the primary school and showed to be very useful, improving children knowledge about air pollution and its effects and stimulating their interest. Conclusions: The associations between levels of air pollutants, air mutagenicity and biomarkers of early effects will be investigated. A tentative model to calculate the global absolute risk of having early biological effects for air pollution and other variables together will be proposed and may be useful to support policy-making and community interventions to protect children from possible health effects of air pollutants.

Keywords: air pollution exposure, biomarkers of early effects, children, public health policy

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1110 Prevalence of Trichomonas Tenax in Patients with Pulmonary Disease and Watersheds and Its Potential Implications for Pulmonary Virus Infection

Authors: Pei Chi Fang, Wei Chen Lin

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Trichomonas tenax is a microaerophilic oral protozoan found in patients with poor oral hygiene. It participates in the inflammatory process of periodontal disease and can potentially be aspirated into the lungs, giving rise to pulmonary trichomoniasis. However, the precise roles of T. tenax in the pulmonary system remain largely unexplored and warrant comprehensive epidemiological investigation. To assess the prevalence of T. tenax infection, we collected bronchoalveolar lavage fluid (BALF) samples from hospitalized patients with lung diseases. A specific nested PCR approach was employed to determine prevalence rates, yielding 21 positive cases out of 61 samples from Ditmanson Medical Foundation Chia-Yi Christian Hospital, and 11 positive cases out of 55 samples from National Cheng Kung University Hospital. Furthermore, there is a critical need for comprehensive data regarding the presence of T. tenax in environmental surface watersheds. In this context, we present findings from investigations in the Yanshuei and Donggang river basins in southern Taiwan, which are crucial sources for public drinking water in the region. In order to elucidate potential implications on pulmonary virus infections, we conducted an analysis of gene expression level changes in H292 cell line after exposure to T. tenax. Our findings revealed significant regulation of multiple virus-related genes, including IFI44L and IFITM3. Ongoing research endeavors are focused on identifying the key components within T. tenax responsible for these observed effects. Crucially, this study lays the groundwork for a preliminary understanding of T. tenax prevalence in patients with pulmonary diseases. It also seeks to establish a meaningful correlation between lung infections and oral hygiene practices, with the ultimate aim of informing distinct treatment and prevention strategies.

Keywords: parasitology, genes, virus, human health, infection, lung

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1109 Sparse Modelling of Cancer Patients’ Survival Based on Genomic Copy Number Alterations

Authors: Khaled M. Alqahtani

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Copy number alterations (CNA) are variations in the structure of the genome, where certain regions deviate from the typical two chromosomal copies. These alterations are pivotal in understanding tumor progression and are indicative of patients' survival outcomes. However, effectively modeling patients' survival based on their genomic CNA profiles while identifying relevant genomic regions remains a statistical challenge. Various methods, such as the Cox proportional hazard (PH) model with ridge, lasso, or elastic net penalties, have been proposed but often overlook the inherent dependencies between genomic regions, leading to results that are hard to interpret. In this study, we enhance the elastic net penalty by incorporating an additional penalty that accounts for these dependencies. This approach yields smooth parameter estimates and facilitates variable selection, resulting in a sparse solution. Our findings demonstrate that this method outperforms other models in predicting survival outcomes, as evidenced by our simulation study. Moreover, it allows for a more meaningful interpretation of genomic regions associated with patients' survival. We demonstrate the efficacy of our approach using both real data from a lung cancer cohort and simulated datasets.

Keywords: copy number alterations, cox proportional hazard, lung cancer, regression, sparse solution

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1108 Contraction and Membrane Potential of C2C12 with GTXs

Authors: Bayan Almofty, Yuto Yamaki, Tadamasa Terai, Sadahito Uto

Abstract:

Culture techniques of skeletal muscle cells are advanced in the field of regenerative medicine and applied research of cultured muscle. As applied research of cultured muscle, myopathy (muscles disease) treatment is expected and development bio of actuator is also expected in biomedical engineering. Grayanotoxins (GTXs) is known as neurotoxins that enhance the permeability of cell membrane for Na ions. Grayanotoxins are extracted from a famous Pieris japonica and Ericaceae as well as a phytotoxin. In this study, we investigated the effect of GTXs on muscle cells (C2C12) contraction and membrane potential. Contraction of myotubes is induced by applied external electrical stimulation. Contraction and membrane potential change of skeletal muscle cells are induced by injection of current. We, therefore, concluded that effect of Grayanotoxins on contraction and membrane potential of C2C12 relate to acute toxicity of GTXs.

Keywords: skeletal muscle cells C2C12, grayanotoxins, contraction, membrane potential, acute toxicity, pytotoxin, motubes

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1107 Using Multiomic Plasma Profiling From Liquid Biopsies to Identify Potential Signatures for Disease Diagnostics in Late-Stage Non-small Cell Lung Cancer (NSCLC) in Trinidad and Tobago

Authors: Nicole Ramlachan, Samuel Mark West

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Lung cancer is the leading cause of cancer-associated deaths in North America, with the vast majority being non-small cell lung cancer (NSCLC), with a five-year survival rate of only 24%. Non-invasive discovery of biomarkers associated with early-diagnosis of NSCLC can enable precision oncology efforts using liquid biopsy-based multiomics profiling of plasma. Although tissue biopsies are currently the gold standard for tumor profiling, this method presents many limitations since these are invasive, risky, and sometimes hard to obtain as well as only giving a limited tumor profile. Blood-based tests provides a less-invasive, more robust approach to interrogate both tumor- and non-tumor-derived signals. We intend to examine 30 stage III-IV NSCLC patients pre-surgery and collect plasma samples.Cell-free DNA (cfDNA) will be extracted from plasma, and next-generation sequencing (NGS) performed. Through the analysis of tumor-specific alterations, including single nucleotide variants (SNVs), insertions, deletions, copy number variations (CNVs), and methylation alterations, we intend to identify tumor-derived DNA—ctDNA among the total pool of cfDNA. This would generate data to be used as an accurate form of cancer genotyping for diagnostic purposes. Using liquid biopsies offer opportunities to improve the surveillance of cancer patients during treatment and would supplement current diagnosis and tumor profiling strategies previously not readily available in Trinidad and Tobago. It would be useful and advantageous to use this in diagnosis and tumour profiling as well as to monitor cancer patients, providing early information regarding disease evolution and treatment efficacy, and reorient treatment strategies in, timethereby improving clinical oncology outcomes.

Keywords: genomics, multiomics, clinical genetics, genotyping, oncology, diagnostics

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1106 Covid-19, Diagnosis with Computed Tomography and Artificial Intelligence, in a Few Simple Words

Authors: Angelis P. Barlampas

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Target: The (SARS-CoV-2) is still a threat. AI software could be useful, categorizing the disease into different severities and indicate the extent of the lesions. Materials and methods: AI is a new revolutionary technique, which uses powered computerized systems, to do what a human being does more rapidly, more easily, as accurate and diagnostically safe as the original medical report and, in certain circumstances, even better, saving time and helping the health system to overcome problems, such as work overload and human fatigue. Results: It will be given an effort to describe to the inexperienced reader (see figures), as simple as possible, how an artificial intelligence system diagnoses computed tomography pictures. First, the computerized machine learns the physiologic motives of lung parenchyma by being feeded with normal structured images of the lung tissue. Having being used to recognizing normal structures, it can then easily indentify the pathologic ones, as their images do not fit to known normal picture motives. It is the same way as when someone spends his free time in reading magazines with quizzes, such as <> and <>. General conclusion: The AI mimics the physiological processes of the human mind, but it does that more efficiently and rapidly and provides results in a few seconds, whereas an experienced radiologist needs many days to do that, or even worse, he is unable to accomplish such a huge task.

Keywords: covid-19, artificial intelligence, automated imaging, CT, chest imaging

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1105 Isolation of Cytotoxic Compound from Tectona grandis Stem to Be Used as Thai Medicinal Preparation for Cancer Treatment

Authors: Onmanee Prajuabjinda, Pakakrong Thondeeying, Jipisute Chunthorng-Orn, Bhanuz Dechayont, Arunporn Itharat

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A Thai medicinal preparation has been used for cancer treatment more than ten years ago in Khampramong Temple. Tectona grandis stem is one ingredient of this Thai medicinal remedy. The ethanolic extract of Tectona grandis stem showed the highest cytotoxic activities against human breast adenocarcinoma (MCF-7), but was less cytotoxic against large cell lung carcinoma (COR-L23) (IC50 = 3.92 and 7.78 µg/ml, respectively). It was isolated by bioassay-guided isolation method. Tectoquinone, a anthraquinone compound was isolated from this plant. This compound showed high specific cytotoxicity against human breast adenocarcinoma (MCF-7), but was less cytotoxic against large cell lung carcinoma (COR-L23)(IC50 =16.15 and 47.56 µg/ml or 72.67 and 214.00 µM, respectively). However, it showed less cytotoxic activity than the crude extract. In conclusion, tectoquinone as a main compound, is not the best cytotoxic compound from Tectona grandis, so there are more active cytotoxic compounds in this extract which should be isolated in the future. Moreover, tectoquinone displayed specific cytotoxicity against only human breast adenocarcinoma (MCF-7) which is a good criterion for cancer treatment.

Keywords: Tectona grandis, SRB assay, cytotoxicity, tectoquinone

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