Search results for: biomarker discovery

Authors: Joseph Gear, Yue Xu, Ernest Foo, Praveen Gauravaran, Zahra Jadidi, Leonie Simpson

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Deep learning methods have been seeing an increasing application to the long-standing security research goal of automatic vulnerability detection for source code. Attention, however, must still be paid to the task of producing vector representations for source code (code embeddings) as input for these deep learning models. Graphical representations of code, most predominantly Abstract Syntax Trees and Code Property Graphs, have received some use in this task of late; however, for very large graphs representing very large code snip- pets, learning becomes prohibitively computationally expensive. This expense may be reduced by intelligently pruning this input to only vulnerability-relevant information; however, little research in this area has been performed. Additionally, most existing work comprehends code based solely on the structure of the graph at the expense of the information contained by the node in the graph. This paper proposes Semantic-enhanced Code Embedding for Vulnerability Discovery (SCEVD), a deep learning model which uses semantic-based feature selection for its vulnerability classification model. It uses information from the nodes as well as the structure of the code graph in order to select features which are most indicative of the presence or absence of vulnerabilities. This model is implemented and experimentally tested using the SARD Juliet vulnerability test suite to determine its efficacy. It is able to improve on existing code graph feature selection methods, as demonstrated by its improved ability to discover vulnerabilities.

Keywords: code representation, deep learning, source code semantics, vulnerability discovery

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Authors: Anjani Kumar Tiwari, Neelam Kumari, Anil Mishra

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The 18-kDa translocator protein (TSPO) previously called as peripheral benzodiazepine receptor, is proven biomarker for variety of neuroinflammation. TSPO is tryptophane rich five transmembranal protein found on outer mitochondrial membrane of steroid synthesising and immunomodulatory cells. In case of neuronal damage or inflammation the expression level of TSPO get upregulated as an immunomodulatory response. By utilizing Benzoxazolone as a basic scaffold, series of TSPO ligands have been designed followed by their screening through in silico studies. Synthesis has been planned by employing convergent methodology in six high yielding steps. For the synthesized ligands the ‘in vitro’ assay was performed to determine the binding affinity in term of Ki. On ischemic rat brain, autoradiography studies were also carried to check the specificity and affinity of the designed radiolabelled ligand for TSPO.Screening was performed on the basis of GScore of CADD based schrodinger software. All the modified and better prospective compound were successfully carried out and characterized by spectroscopic techniques (FTIR, NMR and HRMS). In vitro binding assay showed best binding affinity Ki = 6.1+ 0.3 for TSPO over central benzodiazepine receptor (CBR) Ki > 200. ARG studies indicated higher uptake of two analogues on the lesion side compared with that on the non-lesion side of ischemic rat brains. Displacement experiments with unlabelled ligand had minimized the difference in uptake between the two sides which indicates the specificity of the ligand towards TSPO receptor.

Keywords: TSPO, PET, imaging, Acetamidobenzoxazolone

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Authors: Shima Mahmoudi, Babak Pourakbari, Setareh Mamishi, Mostafa Teymuri, Majid Marjani

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Although cytokine analysis has greatly contributed to the understanding of tuberculosis (TB) pathogenesis, data on cytokine profiles that might distinguish progression from latency of TB infection are scarce. Since PE/PPE proteins are known to induce strong humoral and cellular immune responses, the aim of this study was to evaluate the diagnostic potential of interleukin-2 (IL-2) as biomarker after specific antigen stimulation with PE35 and PPE68 for the discrimination of active and latent tuberculosis infection (LTBI). The production of IL-2 was measured in the antigen-stimulated whole-blood supernatants following stimulation with recombinant PE35 and PPE68. All the patients with active TB and LTBI had positive QuantiFERON-TB Gold in Tube test. The level of IL-2 following stimulation with recombinant PE35 and PPE68 were significantly higher in LTBI group than in patients with active TB infection or control group. The discrimination performance (assessed by the area under ROC curve) for IL-2 following stimulation with recombinant PE35 and PPE68 between LTBI and patients with active TB were 0.837 (95%CI: 0.72-0.97) and 0.75 (95%CI: 0.63-0.89), respectively. Applying the 12.4 pg/mL cut-off for IL-2 induced by PE35 in the present study population resulted in sensitivity of 78%, specificity of 78%, PPV of 78% and NPV of 100%. In addition, a sensitivity of 81%, specificity of 70%, PPV of 67% and 87% of NPV was reported based on the 4.4 pg/mL cut-off for IL-2 induced by PPE68. In conclusion, peptides of the antigen PE35 and PPE68, absent from commonly used BCG strains, stimulated strong IL-2- positive T cell responses in patients with LTBI. This study confirms IL-2 induced by PE35 and PPE68 as a sensitive and specific biomarker and highlights IL-2 as new promising adjunct markers for discriminating of LTBI and Active TB infection.

Keywords: IL-2, PE35, PPE68, tuberculosis

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Authors: Elachouri Mostafa, Fakchich Jamila, Lazaar Jamila, Elmadmad Mohammed, Marhom Mostafa

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Of course, there has been a great growth in scientific information about medicinal plants in recent decades, but in many ways this has proved poor compensation, because such information is accessible, in practice, only to a very few people and anyway, rather little of it is relevant to problems of management and utilization, as encountered in the field. Active compounds are used in most traditional medicines and play an important role in advancing sustainable rural livelihoods through their conservation, cultivation, propagation, marketing and commercialization. Medicinal herbs are great resources for various pharmaceutical compounds and urgent measures are required to protect these plant species from their natural destruction and disappearance. Indeed, there is a real danger of indigenous Arab medicinal practices and knowledge disappearing altogether, further weakening traditional Arab culture and creating more insecurity, as well as forsaking a resource of inestimable economic and health care importance. As scientific approach, the ethnopharmacological investigation remains the principal way to improve, evaluate, and increase the odds of finding of biologically active compounds derived from medicinal plants. As developing country, belonging to the Mediterranean basin, Morocco country is endowed with resources of medicinal and aromatic plants. These plants have been used over the millennia for human welfare, even today. Besides, Morocco has a large plant biodiversity, in fact, its medicinal flora account more than 4200 species growing on various bioclimatic zones from subhumide to arid and Saharan. Nevertheless, the human and animal pressure resulting from the increase of rural population needs has led to degradation of this patrimony. In this paper, we focus our attention on ethnopharmacological studies carried out in Morocco. The goal of this work is to clarify the importance of herbs as platform for drugs discovery and further development, to highlight the importance of ethnopharmacological study as approach on discovery of natural products in the health care field, and to discuss the limit of ethnopharmacological investigation of drug discovery in Morocco.

Keywords: Morocco, medicinal plants, ethnopharmacology, natural products, drug-discovery

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Authors: Supannika Klangphukhiew, Roongnapa Srichana, Rina Patramanon

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Cortisol has been used as a well-known commercial stress biomarker. A homeostasis response to psychological stress is indicated by an increased level of cortisol produced in hypothalamus-pituitary-adrenal (HPA) axis. Chronic psychological stress contributing to the high level of cortisol relates to several health problems. In this study, the cortisol biosensor was fabricated that mimicked the natural receptors. The artificial antibodies were prepared using molecular imprinted polymer technique that can imitate the performance of natural anti-cortisol antibody with high stability. Cortisol-molecular imprinted polymer (cortisol-MIP) was obtained using the multi-step swelling and polymerization protocol with cortisol as a target molecule combining methacrylic acid:acrylamide (2:1) with bisacryloyl-1,2-dihydroxy-1,2-ethylenediamine and ethylenedioxy-N-methylamphetamine as cross-linkers. Cortisol-MIP was integrated to the sensor. It was coated on the disposable screen-printed carbon electrode (SPCE) for portable electrochemical analysis. The physical properties of Cortisol-MIP were characterized by means of electron microscope techniques. The binding characteristics were evaluated via covalent patterns changing in FTIR spectra which were related to voltammetry response. The performance of cortisol-MIP modified SPCE was investigated in terms of detection range, high selectivity with a detection limit of 1.28 ng/ml. The disposable cortisol biosensor represented an application of MIP technique to recognize steroids according to their structures with feasibility and cost-effectiveness that can be developed to use in point-of-care.

Keywords: stress biomarker, cortisol, molecular imprinted polymer, screen-printed carbon electrode

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Authors: Melahat Çevik

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The discovery of fabric has a quite old historical perspective because of veiling, heating and shelter needs of human. Since the days which fashion has a say, this situation has pasted beyond needs and has become status symbols. For the theater art drama which tell people by people, in the concern of reflecting daily life there will be such regards also we may see alternative products to artistically reshaped fabric. The stage is determined in the consensus of costume designer and director. Costume Designer does the research, taking into account the alternative products. Approaching nature as inventor, discovering products, shapes the work because in this work, cost is considerable. All types of fabric will be used but also new materials which are not presented to clothing industry yet are of great importance. In the discovery of new materials there priorities of the costume designer. In the scene everything should be determined in the axis of actor. The material discussed should have positive qualities which allow the performer to move and invigorate him or her in terms of physical and also should be positive in terms of health. This point must be approached in a more precise in high action plays and the obtained material should be tested before the presentation process.

Keywords: fabric, stage design, alternative materials, clothing industry

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Authors: Abhimanyu Thakur, Youngjin Lee

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Glioma is a lethal brain cancer whose early diagnosis and prognosis are limited due to the dearth of a suitable technique for its early detection. Current approaches, including magnetic resonance imaging (MRI), computed tomography (CT), and invasive biopsy for the diagnosis of this lethal disease, hold several limitations, demanding an alternative method. Recently, extracellular vesicles (EVs) have been used in numerous biomarker studies, majorly exosomes and microvesicles (MVs), which are found in most of the cells and biofluids, including blood, cerebrospinal fluid (CSF), and urine. Remarkably, glioma cells (GMs) release a high number of EVs, which are found to cross the blood-brain-barrier (BBB) and impersonate the constituents of parent GMs including protein, and lncRNA; however, biophysical properties of EVs have not been explored yet as a biomarker for glioma. We isolated EVs from cell culture conditioned medium of GMs and regular primary culture, blood, and urine of wild-type (WT)- and glioma mouse models, and characterized by nano tracking analyzer, transmission electron microscopy, immunogold-EM, and differential light scanning. Next, we measured the biophysical parameters of GMs-EVs by using atomic force microscopy. Further, the functional constituents of EVs were examined by FTIR and Raman spectroscopy. Exosomes and MVs-derived from GMs, blood, and urine showed distinction biophysical parameters (roughness, adhesion force, and stiffness) and different from that of regular primary glial cells, WT-blood, and -urine, which can be attributed to the characteristic functional constituents. Therefore, biophysical features can be potential diagnostic biomarkers for glioma.

Keywords: glioma, extracellular vesicles, exosomes, microvesicles, biophysical properties

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Authors: Doaa Hashad, Amany Elyamany, Perihan Salem

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Introduction: Hepatitis C virus infection (HCV) constitutes a serious dilemma that has an impact on the health of millions of Egyptians. Hepatitis C virus related hepatocellular carcinoma (HCV-HCC) is a crucial consequence of HCV that represents the third cause of cancer-related deaths worldwide. Aim of the study: assess the use of mitochondrial DNA (mtDNA) content as a non-invasive molecular biomarker in hepatitis c virus related hepatocellular carcinoma (HCV-HCC). Methods: A total of 135 participants were enrolled in the study. Volunteers were assigned to one of three groups equally; a group of HCV related cirrhosis (HCV-cirrhosis), a group of HCV-HCC and a control group of age- and sex- matched healthy volunteers with no evidence of liver disease. mtDNA was determined using a quantitative real-time PCR technique. Results: mtDNA content was lowest in HCV-HCC cases. No statistically significant difference was observed between the group of HCV-cirrhosis and the control group as regards mtDNA level. HCC patients with multi-centric hepatic lesions had significantly lower mtDNA content. On using receiver operating characteristic curve analysis, a cutoff of 34 was assigned for mtDNA content to distinguish between HCV-HCC and HCV-cirrhosis patients who are not yet complicated by malignancy. Lower mtDNA was associated with greater HCC risk on using healthy controls, HCV-cirrhosis, or combining both groups as a reference group. Conclusions: mtDNA content might constitute a non-invasive molecular biomarker that reflects tumor burden in HCV-HCC cases and could be used as a predictor of HCC risk in patients of HCV-cirrhosis. In addition, the non significant difference of mtDNA level between HCV-cirrhosis patients and healthy controls could eliminate the grey zone created by the use of AFP in some cirrhotic patients.

Keywords: DNA copy number, HCC, HCV, mitochondrial

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Authors: Ying Li, Rui Hu, Shizhen Chen, Xin Zhou, Yunhuang Yang

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Prostate cancer is one of the leading causes of cancer-related death among men. Prostate-specific antigen (PSA), a specific product of prostatic epithelial cells, is an important indicator of prostate cancer. Though PSA is not a specific serum biomarker for the screening of prostate cancer, it is recognized as an indicator for prostate cancer recurrence and response to therapy for patient’s post-prostatectomy. Since radical prostatectomy eliminates the source of PSA production, serum PSA levels fall below 50 pg/mL, and may be below the detection limit of clinical immunoassays (current clinical immunoassay lower limit of detection is around 10 pg/mL). Many clinical studies have shown that intervention at low PSA levels was able to improve patient outcomes significantly. Therefore, ultra-sensitive and precise assays that can accurately quantify extremely low levels of PSA (below 1-10 pg/mL) will facilitate the assessment of patients for the possibility of early adjuvant or salvage treatment. Currently, the commercially available ultra-sensitive ELISA kit (not used clinically) can only reach a detection limit of 3-10 pg/mL. Other platforms developed by different research groups could achieve a detection limit as low as 0.33 pg/mL, but they relied on sophisticated instruments to get the final readout. Herein we report a microfluidic platform for point-of-care (POC) detection of PSA with a detection limit of 0.5 pg/mL and without the assistance of any equipment. This platform is based on a previously reported volumetric-bar-chart chip (V-Chip), which applies platinum nanoparticles (PtNPs) as the ELISA probe to convert the biomarker concentration to the volume of oxygen gas that further pushes the red ink to form a visualized bar-chart. The length of each bar is used to quantify the biomarker concentration of each sample. We devised a long reading channel V-Chip (LV-Chip) in this work to achieve a wide detection window. In addition, LV-Chip employed a unique enzyme-free ELISA probe that enriched PtNPs significantly and owned 500-fold enhanced catalytic ability over that of previous V-Chip, resulting in a significantly improved detection limit. LV-Chip is able to complete a PSA assay for five samples in 20 min. The device was applied to detect PSA in 50 patient serum samples, and the on-chip results demonstrated good correlation with conventional immunoassay. In addition, the PSA levels in finger-prick whole blood samples from healthy volunteers were successfully measured on the device. This completely stand-alone LV-Chip platform enables convenient POC testing for patient follow-up in the physician’s office and is also useful in resource-constrained settings.

Keywords: point-of-care detection, microfluidics, PSA, ultra-sensitive

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Authors: V. Kuzhandai Velu, R. Ramesh

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Background and objectives: Acute myocardial infarction (AMI) is the most common cause of mortality and morbidity. Over the last decade, microRNAs (miRs) have emerged as a potential marker for detecting AMI. The current study evaluates the kinetics and importance of miRs in the differential diagnosis of ST-segment elevated MI (STEMI) and non-STEMI (NSTEMI) and its correlation to conventional biomarkers and to predict the immediate outcome of AMI for arrhythmias and left ventricular (LV) dysfunction. Materials and Method: A total of 100 AMI patients were recruited for the study. Routine cardiac biomarker and miRNA levels were measured during diagnosis and serially at admission, 6, 12, 24, and 72hrs. The baseline biochemical parameters were analyzed. The expression of miRs was compared between STEMI and NSTEMI at different time intervals. Diagnostic utility of miR-1, miR-133, miR-208, and miR-499 levels were analyzed by using RT-PCR and with various diagnostics statistical tools like ROC, odds ratio, and likelihood ratio. Results: The miR-1, miR-133, and miR-499 showed peak concentration at 6 hours, whereas miR-208 showed high significant differences at all time intervals. miR-133 demonstrated the maximum area under the curve at different time intervals in the differential diagnosis of STEMI and NSTEMI which was followed by miR-499 and miR-208. Evaluation of miRs for predicting arrhythmia and LV dysfunction using admission sample demonstrated that miR-1 (OR = 8.64; LR = 1.76) and miR-208 (OR = 26.25; LR = 5.96) showed maximum odds ratio and likelihood respectively. Conclusion: Circulating miRNA showed a highly significant difference between STEMI and NSTEMI in AMI patients. The peak was much earlier than the conventional biomarkers. miR-133, miR-208, and miR-499 can be used in the differential diagnosis of STEMI and NSTEMI, whereas miR-1 and miR-208 could be used in the prediction of arrhythmia and LV dysfunction, respectively.

Keywords: myocardial infarction, cardiac biomarkers, microRNA, arrhythmia, left ventricular dysfunction

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Authors: Ahmed Al-Saadi, Ali Hassanpour, Tariq Mahmud

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The main objective of this study is to investigate ways to reduce the aerodynamic drag coefficient and to increase the stability of the full-size Sport Utility Vehicle using three-dimensional Computational Fluid Dynamics (CFD) simulation. The baseline model in the simulation was the Land Rover Discovery 4. Many aerodynamic devices and external design modifications were used in this study. These reduction aerodynamic techniques were tested individually or in combination to get the best design. All new models have the same capacity and comfort of the baseline model. Uniform freestream velocity of the air at inlet ranging from 28 m/s to 40 m/s was used. ANSYS Fluent software (version 16.0) was used to simulate all models. The drag coefficient obtained from the ANSYS Fluent for the baseline model was validated with experimental data. It is found that the use of modern aerodynamic add-on devices and modifications has a significant effect in reducing the aerodynamic drag coefficient.

Keywords: aerodynamics, RANS, sport utility vehicle, turbulent flow

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Authors: Manssour Habbash, Srinivasa Rao Idapalapati

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Although writing is a multifaceted task, teaching writing is a demanding task basically for two reasons: Grammar and Syntax. This article provides a method of teaching writing that was found to be effective in improving students’ academic writing composition skill. The article explains the concepts of ‘guided-discovery’ and ‘guided-construction’ upon which a method of teaching writing is grounded and developed. Providing a brief commentary on what the core could mean primarily, the article presents an exposition of understanding and identifying the core and building upon the core that can demonstrate the way a teacher can make use of the concepts in teaching for improving the writing skills of their students. The method is an adaptation of grammar translation method that has been improvised to suit to a student-centered classroom environment. An intervention of teaching writing through this method was tried out with positive outcomes in formal classroom research setup, and in view of the content’s quality that relates more to the classroom practices and also in consideration of its usefulness to the practicing teachers the process and the findings are presented in a narrative form along with the results in tabular form.

Keywords: core of a text, guided construction, guided discovery, theme of a text

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Authors: Neelam Rashid, Muhammad Zafar, Mushtaq Ahmad, Khafsa Malik, Syed Nasar Shah

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The present study was conducted to study the role of medicinal plants used to cure different ailments in Azad Kashmir. Various ethno medicinal surveys were carried out during 2016 to enlist the uses of plants against various ailments by rural communities of the area. Information was obtained from 60 local people including 45 males (10 traditional health practitioners) and 15 females by semi structured interviews and group discussions. 65 plant species belonging to 45 families were reported. The dominant plant habit was herbaceous (56%) while decoction was the most common method of utilization (40%). The most cited turmoil was the gastrointestinal disorders. The data obtained were analyzed using ethno medicinal indices such as FL, UV, ICF, FC, and RFC. Results revealed that various species had numerous uses in curing of diseases. So conservation of biodiversity of these medicinal plants and traditional knowledge can play important role in improving the local health conditions of rural people and modern drug discovery and development.

Keywords: medicinal plants, ailments, drug, health, traditional

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Authors: Anahita Farhang Ghahfarokhi, Alessandro Berti, Wil M.P. van der Aalst

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Process mining provides ways to analyze business processes. Common process mining techniques consider the process as a whole. However, in real-life business processes, different behaviors exist that make the overall process too complex to interpret. Process comparison is a branch of process mining that isolates different behaviors of the process from each other by using process cubes. Process cubes organize event data using different dimensions. Each cell contains a set of events that can be used as an input to apply process mining techniques. Existing work on process cubes assume single case notions. However, in real processes, several case notions (e.g., order, item, package, etc.) are intertwined. Object-centric process mining is a new branch of process mining addressing multiple case notions in a process. To make a bridge between object-centric process mining and process comparison, we propose a process cube framework, which supports process cube operations such as slice and dice on object-centric event logs. To facilitate the comparison, the framework is integrated with several object-centric process discovery approaches.

Keywords: multidimensional process mining, mMulti-perspective business processes, OLAP, process cubes, process discovery, process mining

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Authors: Mai Ghazal, Ahmed Hammad

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Cost overruns in construction projects are considered as worldwide challenges since the cost performance is one of the main measures of success along with schedule performance. To overcome this problem, studies were conducted to investigate the cost overruns' factors, also projects' historical data were analyzed to extract new and useful knowledge from it. This research is studying and analyzing the effect of some factors causing cost overruns using the historical data from completed construction projects. Then, using these factors to estimate the probability of cost overrun occurrence and predict its percentage for future projects. First, an intensive literature review was done to study all the factors that cause cost overrun in construction projects, then another review was done for previous researcher papers about mining process in dealing with cost overruns. Second, a proposed data warehouse was structured which can be used by organizations to store their future data in a well-organized way so it can be easily analyzed later. Third twelve quantitative factors which their data are frequently available at construction projects were selected to be the analyzed factors and suggested predictors for the proposed model.

Keywords: construction management, construction projects, cost overrun, cost performance, data mining, data warehousing, knowledge discovery, knowledge management

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Authors: G. H. Haddadi, S. Sajadi, R. Fardid, Z. Haddadi

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The heart is a radiosensitive organ, and its damage is a dose-limiting factor in radiotherapy. Different side effects including vascular plaque and heart fibrosis occur in patients with thorax irradiation. The present study aimed to evaluate the radioprotective efficacy of Hesperidin (HES), a naturally occurring citrus flavanoglycone, against γ-radiation induced tissue damage in the heart of male rats. Sixty-eight rats were divided into four groups. The rats in group 1 received PBS, and those in group 2 received HES. Also, the rats in group 3 received PBS and underwent γ-irradiation, and those in group 4 received HES and underwent γ-irradiation. They were exposed to 20 Gy γ-radiation using a single fraction cobalt-60 unit, and the dose of Hesperidin was (100 mg/kg/d, orally) for 7 days prior irradiation. Each group was divided into two subgroups. Samplings of rats in subgroup A was done 4-6 hours after irradiation. The samples were sent to laboratory for determination of Troponin’s I (TnI) serum level changes as a cardiac biomarker. The remaining animals (subgroups B) were sacrificed 8 weeks after radiotherapy for histopathological evaluation. In group 3, TnI obviously increased in comparison with group 1 (p < 0.05). The comparison of groups 1 and 4 showed no significant difference. Evaluation of histopathological parameters in subgroup B showed significant differences between groups 1 and 3 in some of the cases. Inflammation (p=0.008), pericardial effusion (p=0.001) and vascular plaque (p=0.001) increased in the rats exposed to 20 Gy γ-irradiation. Using oral administration of HES significantly decreased all the above factors when compared to group 4 (P > 0.016). Administration of 100 mg/kg/day Hesperidin for 7 days resulted in decreased Troponin I and radiation heart injury. This agent may have protective effects against radiation-induced heart damage.

Keywords: hesperidin, radioprotector, troponin I, cardiac inflammation, vascular plaque

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Authors: Vani Singhal, Jitendra Parmar, Satyendra Singh Chouhan

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Unseen class discovery has now become an important part of a machine-learning algorithm to judge new classes. Unseen classes are the classes on which the machine learning model is not trained on. With the advancement in technology and AI replacing humans, the amount of data has increased to the next level. So while implementing a model on real-world examples, we come across unseen new classes. Our aim is to find the number of unseen classes by using a hierarchical-based active learning algorithm. The algorithm is based on hierarchical clustering as well as active sampling. The number of clusters that we will get in the end will give the number of unseen classes. The total clusters will also contain some clusters that have unseen classes. Instead of first discovering unseen classes and then finding their number, we directly calculated the number by applying the algorithm. The dataset used is for intent classification. The target data is the intent of the corresponding query. We conclude that when the machine learning model will encounter real-world data, it will automatically find the number of unseen classes. In the future, our next work would be to label these unseen classes correctly.

Keywords: active sampling, hierarchical clustering, open world learning, unseen class discovery

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Authors: Reza Fardid, Aliyeh Alipour

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Introduction: Coronary heart disease (CHD) is the most common and deadliest diseases. A coronary angiography is an important tool for the diagnosis and treatment of this disease. Because angiography is performed by exposure to ionizing radiation, it can lead to harmful effects. Ionizing radiation induces double-stranded breaks in DNA, which is a potentially life-threatening injury. The purpose of the present study is an investigation of the phosphorylation of histone H2AX in the location of the double-stranded break in Peripheral blood lymphocytes as an indication of Biological effects of radiation on angiography patients. Materials and Methods: This method is based on measurement of the phosphorylation of histone (gamma-H2AX, gH2AX) level on serine 139 after formation of DNA double-strand break. 5 cc of blood from 24 patients with angiography were sampled before and after irradiation. Blood lymphocytes were removed, fixed and were stained with specific ϒH2AX antibodies. Finally, ϒH2AX signal as an indicator of the double-strand break was measured with Flow Cytometry Technique. Results and discussion: In all patients, an increase was observed in the number of breaks in double-stranded DNA after irradiation (20.15 ± 14.18) compared to before exposure (1.52 ± 0.34). Also, the mean of DNA double-strand break was showed a linear correlation with DAP. However, although induction of DNA double-strand breaks associated with radiation dose in patients, the effect of individual factors such as radiosensitivity and regenerative capacity should not be ignored. If in future we can measure DNA damage response in every patient angiography and it will be used as a biomarker patient dose, will look very impressive on the public health level. Conclusion: Using flow cytometry readings which are done automatically, it is possible to detect ϒH2AX in the number of blood cells. Therefore, the use of this technique could play a significant role in monitoring patients.

Keywords: coronary angiography, DSB of DNA, ϒH2AX, ionizing radiation

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Authors: Shasline Gedeon, Tiffany W. Ardley, Ying Wang, Nathan J. Gesmundo, Katarina A. Sarris, Ana L. Aguirre

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Drug discovery and delivery involve drug targeting, an approach that helps find a drug against a chosen target through high throughput screening and other methods by way of identifying the physical properties of the potential lead compound. Physical properties of potential drug candidates have been an imperative focus since the unveiling of Lipinski's Rule of 5 for oral drugs. Throughout a compound's journey from discovery, clinical phase trials, then becoming a classified drug on the market, the desirable properties are optimized while minimizing/eliminating toxicity and undesirable properties. In the pharmaceutical industry, the ability to generate molecules in parallel with maximum efficiency is a substantial factor achieved through sp²-sp² carbon coupling reactions, e.g., Suzuki Coupling reactions. These reaction types allow for the increase of aromatic fragments onto a compound. More recent literature has found benefits to decreasing aromaticity, calling for more sp³-sp² carbon coupling reactions instead. The objective of this project is to provide a comparison between various sp³-sp² carbon coupling methods and reaction conditions, collecting data on production of the desired product. There were four different coupling methods being tested amongst three cores and 4-5 installation groups per method; each method ran under three distinct reaction conditions. The tested methods include the Photoredox Decarboxylative Coupling, the Photoredox Potassium Alkyl Trifluoroborate (BF3K) Coupling, the Photoredox Cross-Electrophile (PCE) Coupling, and the Weix Cross-Electrophile (WCE) Coupling. The results concluded that the Decarboxylative method was very difficult in yielding product despite the several literature conditions chosen. The BF3K and PCE methods produced competitive results. Amongst the two Cross-Electrophile coupling methods, the Photoredox method surpassed the Weix method on numerous accounts. The results will be used to build future libraries.

Keywords: drug discovery, high throughput chemistry, photoredox chemistry, sp³-sp² carbon coupling methods

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Authors: Dwitya Elvira, Raveinal Masri, Rohayat Bilmahdi

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Human Immunodeficiency Virus (HIV) pandemic increased significantly worldwide. The rise in cases of HIV/AIDS was also followed by an increase in the incidence of opportunistic infection, with tuberculosis being the most opportunistic infection found in HIV/AIDS and the main cause of mortality in HIV/AIDS patients. Diagnosis of tuberculosis in HIV/AIDS patients is often difficult because of the uncommon symptom in HIV/AIDS patients compared to those without the disease. Thus, diagnostic tools are required that are more effective and efficient to diagnose tuberculosis in HIV/AIDS. CXCL-10/IP-10 is a chemokine that binds to the CXCR3 receptor found in HIV/AIDS patients with a weakened immune system. Tuberculosis infection in HIV/AIDS activates chemokine IP-10 in urine, which is used as a marker for diagnosis of infection. The aim of this study was to prove whether IP-10 urine can be a biomarker diagnosis of active lung tuberculosis in HIV-AIDS patients. Design of this study is a cross sectional study involving HIV/AIDS patients with lung tuberculosis as the subject of this study. Forty-seven HIV/AIDS patients with tuberculosis based on clinical and biochemical laboratory were asked to collect urine samples and IP-10/CXCL-10 urine being measured using ELISA method with 18 healthy human urine samples as control. Forty-seven patients diagnosed as HIV/AIDS were included as a subject of this study. HIV/AIDS were more common in male than in women with the percentage in male 85.1% vs. 14.5% of women. In this study, most diagnosed patients were aged 31-40 years old, followed by those 21-30 years, and > 40 years old, with one case diagnosed at age less than 20 years of age. From the result of the urine IP-10 using ELISA method, there was significant increase of the mean value of IP-10 urine in patients with TB-HIV/AIDS co-infection compared to the healthy control with mean 61.05 pg/mL ± 78.01 pg/mL vs. mean 17.2 pg/mL. Based on this research, there was significant increase of urine IP-10/CXCL-10 in active lung tuberculosis with HIV/AIDS compared to the healthy control. From this finding, it is necessary to conduct further research into whether urine IP-10/CXCL-10 plays a significant role in TB-HIV/AIDS co-infection, which can also be used as a biomarker in the early diagnosis of TB-HIV.

Keywords: chemokine, HIV/AIDS, IP-10 urine, tuberculosis

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Authors: Zahrasadat Hosseini, Jie Yuan

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Point-of-care (POC) diagnostic devices based on lab-on-a-chip (LOC) technology have the potential to revolutionize medical diagnostics. However, the development of an ideal microfluidic system based on LOC technology for diagnostics purposes requires overcoming several obstacles, such as improving sensitivity, selectivity, portability, cost-effectiveness, and prototyping methods. While numerous studies have introduced technologies and systems that advance these criteria, existing systems still have limitations. Electrochemical enzyme-linked immunosorbent assay (e-ELISA) in a LOC device offers numerous advantages, including enhanced sensitivity, decreased turnaround time, minimized sample and analyte consumption, reduced cost, disposability, and suitability for miniaturization, integration, and multiplexing. In this study, we present a novel design and fabrication method for a microfluidic diagnostic platform that integrates screen-printed electrochemical carbon/silver chloride electrodes on flexible printed circuit boards with flexible, multilayer, polydimethylsiloxane (PDMS) microfluidic networks to accurately manipulate and pre-immobilize analytes for performing electrochemical enzyme-linked immunosorbent assay (e-ELISA) for multiplexed quantification of blood serum biomarkers. We further demonstrate fast, cost-effective prototyping, as well as accurate and reliable detection performance of this device for quantification of interleukin-6-spiked samples through electrochemical analytics methods. We anticipate that our invention represents a significant step towards the development of user-friendly, portable, medical-grade, POC diagnostic devices.

Keywords: lab-on-a-chip, point-of-care diagnostics, electrochemical ELISA, biomarker quantification, fast prototyping

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Authors: Zahrasadat Hosseini, Jie Yuan

Abstract:

Point-of-care (POC) diagnostic devices based on lab-on-a-chip (LOC) technology have the potential to revolutionize medical diagnostics. However, the development of an ideal microfluidic system based on LOC technology for diagnostics purposes requires overcoming several obstacles, such as improving sensitivity, selectivity, portability, cost-effectiveness, and prototyping methods. While numerous studies have introduced technologies and systems that advance these criteria, existing systems still have limitations. Electrochemical enzyme-linked immunosorbent assay (e-ELISA) in a LOC device offers numerous advantages, including enhanced sensitivity, decreased turnaround time, minimized sample and analyte consumption, reduced cost, disposability, and suitability for miniaturization, integration, and multiplexing. In this study, we present a novel design and fabrication method for a microfluidic diagnostic platform that integrates screen-printed electrochemical carbon/silver chloride electrodes on flexible printed circuit boards with flexible, multilayer, polydimethylsiloxane (PDMS) microfluidic networks to accurately manipulate and pre-immobilize analytes for performing electrochemical enzyme-linked immunosorbent assay (e-ELISA) for multiplexed quantification of blood serum biomarkers. We further demonstrate fast, cost-effective prototyping, as well as accurate and reliable detection performance of this device for quantification of interleukin-6-spiked samples through electrochemical analytics methods. We anticipate that our invention represents a significant step towards the development of user-friendly, portable, medical-grade POC diagnostic devices.

Keywords: lab-on-a-chip, point-of-care diagnostics, electrochemical ELISA, biomarker quantification, fast prototyping

Procedia PDF Downloads 56

Authors: Michio Kurosu

Abstract:

Alterations in glycosylation not only directly impact cell growth and survival but also facilitate tumor-induced immunomodulation and eventual metastasis. Identification of cell type-specific glycoconjugates (tumor markers) has led to the discovery of new assay systems for certain cancers via immunodetection reagents. N- and O-linked glycans are the most abundant forms of glycoproteins. Recent studies of cancer immunotherapy are based on the immunogenicity of truncated O-glycan chains (e.g., Tn, sTn, T, and sLea/x). The prevalence of N-linked glycan changes in the development of tumor cells is known; however, therapeutic antibodies against N-glycans have not yet been developed. This is due to the lack of specificity of N-linked glycans between normal/healthy and cancer cells. Abnormal branching of N-linked glycans has been observed, particularly in solid cancer cells. While the discovery of drug-like glycosyltransferase inhibitors that block the biosynthesis of specific branching has a very low likelihood of success, altered glycosylation levels can be exploited by suppressing N-glycan biosynthesis through the inhibition of dolichyl-phosphate N-acetylglucosaminephosphotransferase1 (DPAGT1) activity. Inhibition of DPAGT1 function leads to changes of O-glycosylation on proteins associated with mitochondria and zinc finger binding proteins (indirect effects). On the basis of dynamic crosstalk between DPAGT1 and Snail/Slung/ZEB1 (a family of transcription factors that promote the repression of the adhesion molecules), we have developed pharmacologically acceptable selective DPAGT1 inhibitors. Tunicamycin kills a wide range of cancer and healthy cells in a non-selective manner. In sharp contrast, our DPAGT1 inhibitors display strong cytostatic effects against 16 solid cancers, which require the overexpression of DPAGT1 in their progression but do not affect the cell viability of healthy cells. The identified DPAGT1 inhibitors possess impressive anti-metastatic ability in various solid cancer cell lines and induce their mitochondrial structural changes, resulting in apoptosis. A prototype DPAGT1 inhibitor, APPB has already been proven to shrink solid tumors (e.g., pancreatic cancers, triple-negative breast cancers) in vivo while suppressing metastases and has strong synergistic effects when combined with current cytotoxic drugs (e.g., paclitaxel). At this conference, our discovery of selective DPAGT1 inhibitors with drug-like properties and proof-of-pharmaceutical concept studies of a novel DPAGT1 inhibitor are presented.

Keywords: DPAGT1 inhibitors, anti-metastatic drugs, natural product based drug designs, cytostatic effects

Procedia PDF Downloads 43

Authors: Harumi Katayama, Mina Suzuki, Taeko Muramatsu, Yui Shimogawa, Yoshimi Mizushima, Mitsuo Hiramatsu, Kimitsugu Nakamura, Takeshi Suzue

Abstract:

Purpose: There are very often footbaths in the hot-spring area as culture from old days in Japan. This culture moderately supported mental and physical health among people. In Japanese hospitals, nurses provide footbath for severe patients to mental comfortable. However, there are only a few evidences effect of footbath for mental comfortable. In this presentation, we show the effect of stress relief of the footbath using biomarker among 35 college students in volunteer. Methods: The experiment was designed in two groups of the footbath group and the simple relaxation group randomly. As mental load, Kraepelin test was given to the students beforehand. Ultra-weak chemiluminescence (UCL) in saliva and self-administered liner scale measurable emotional state were measured on four times concurrently; there is before and after the mental load, after the stress relief, and 30 minutes after the stress relief. The scale that measured emotional state was consisted of 7 factors; there is excitement, relaxation, vigorous, fatigue, tension, calm, and sleepiness with 22 items. ANOVA was calculated effect of the footbath for stress relief. Results: The level of UCL (photons/100sec) was significantly increased in response on both groups after mental load. After the two types of stress relief, UCL (photons/100sec) of footbath group was significantly decreased compared to simple relaxation group. Score of sleepiness and relaxation were significantly increased after the stress relief in the footbath group than the simple relaxation group. However, score of excitement, vigorous, tension, and calm were exhibit the same degree of decrease after the stress relief on both group. Conclusion: It was suggested that salivary UCL may be a sensitive biomarker for mild stress relief as nursing care. In the future, we will measure using UCL to evaluate as stress relief for inpatients, outpatients, or general public as the subjects.

Keywords: bio-marker, footbath, Japan, stress relief

Procedia PDF Downloads 297

Authors: S. Nandagopalan, N. Pradeep

Abstract:

The aim of this paper is to propose a general framework for storing, analyzing, and extracting knowledge from two-dimensional echocardiographic images, color Doppler images, non-medical images, and general data sets. A number of high performance data mining algorithms have been used to carry out this task. Our framework encompasses four layers namely physical storage, object identification, knowledge discovery, user level. Techniques such as active contour model to identify the cardiac chambers, pixel classification to segment the color Doppler echo image, universal model for image retrieval, Bayesian method for classification, parallel algorithms for image segmentation, etc., were employed. Using the feature vector database that have been efficiently constructed, one can perform various data mining tasks like clustering, classification, etc. with efficient algorithms along with image mining given a query image. All these facilities are included in the framework that is supported by state-of-the-art user interface (UI). The algorithms were tested with actual patient data and Coral image database and the results show that their performance is better than the results reported already.

Keywords: active contour, Bayesian, echocardiographic image, feature vector

Procedia PDF Downloads 415

Authors: Mehravar Javid

Abstract:

This article delves straight into the fascinating role of dream interpretation in psychotherapy, particularly in the context of trauma and healing. By applying a detailed case study of a 19-year-old Iranian woman who has been undergoing therapy, it can explore to what extent her vivid and symbolic dreams – featuring mermaids, hanging fetuses, and themes of control and domination – serve as a reflection of her innermost fears, unresolved traumas, and struggles with identity and sexuality. Another fact to be highlighted is that the dreams, rich in metaphor and symbolism, offer a unique outlook into the patient's subconscious mind, revealing layers of her psychological state that might otherwise remain obscured and vague. On the other hand, the article examines how the therapist navigates these dreamscapes by utilizing them as a tool to understand and address the patient's deep-seated emotional conflicts, traumatic experiences, and identity issues. By analyzing these dreams, we can demonstrate how such dreams can be a crucial part of the healing process, providing insights that facilitate emotional recovery and self-discovery. This discovery underscores the significance of dreams in psychotherapy, highlighting their potential as a powerful medium for unraveling the complexities of the human psyche and aiding in the journey toward mental health and recovery.

Keywords: dream, interpreting, trauma, healing

Procedia PDF Downloads 41

Authors: Alyona Cerfontyne, Levita D'Souza, Lefteris Patlamazoglou

Abstract:

Unlike adoption and donor-assisted reproduction, misattributed paternity occurring within the context of spontaneous conception and outside of formally recognised practices of having a child remains largely an understudied phenomenon. In adulthood, to discover misattributed paternity, i.e., that the man you call your father is not related to you genetically, can have profound implications for everyone affected. Until the advent of direct-to-consumer DNA testing 20 years ago, such discoveries were relatively rare. Despite the growing number of individuals uncovering their biogenetic paternity through genetic testing, there is very limited research on misattributed paternity from the perspective of adult children affected by it. No research exists on how to support these individuals through counselling post-discovery. Framed as insider action research, this study aimed to explore the perceived psychosocial consequences of misattributed paternity discoveries and coping strategies used by individuals who discover their misattributed paternity status in adulthood. In total, 12 individuals with misattributed paternity participated in semi-structured interviews in July-August 2022. The collected data was analysed using reflexive thematic analysis. The study’s results indicate that discovering misattributed paternity in adulthood can be likened to a watershed moment forever changing the trajectory of one’s life. Psychological experiences consistent with trauma, as well as grief and loss, re-evaluation of close family relationships, reestablishment of one’s identity, as well as experiencing a profound need to belong are the key themes emerging from the analysis of psychosocial experiences. Post-discovery, individuals with misattributed paternity employ a wide range of emotional and problem-focused coping strategies, amongst which seeking connection with those who understand, searching for information on the new biogenetic family and finding new meanings to life are most prominent. The study contributes both to the academic and practical knowledge of experiences of misattributed paternity and highlights the importance of further research on the topic.

Keywords: discovery of misattributed paternity, misattributed paternity, paternal discrepancy, psychosocial consequences, coping

Procedia PDF Downloads 55

Authors: S. Nandagopalan, N. Pradeep

Abstract:

The aim of this paper is to propose a general framework for storing, analyzing, and extracting knowledge from two-dimensional echocardiographic images, color Doppler images, non-medical images, and general data sets. A number of high performance data mining algorithms have been used to carry out this task. Our framework encompasses four layers namely physical storage, object identification, knowledge discovery, user level. Techniques such as active contour model to identify the cardiac chambers, pixel classification to segment the color Doppler echo image, universal model for image retrieval, Bayesian method for classification, parallel algorithms for image segmentation, etc., were employed. Using the feature vector database that have been efficiently constructed, one can perform various data mining tasks like clustering, classification, etc. with efficient algorithms along with image mining given a query image. All these facilities are included in the framework that is supported by state-of-the-art user interface (UI). The algorithms were tested with actual patient data and Coral image database and the results show that their performance is better than the results reported already.

Keywords: active contour, bayesian, echocardiographic image, feature vector

Procedia PDF Downloads 389

Authors: Ambrish Tiwari, Sudhasini Panda, Archana Singh, Kalpana Luthra, S. K. Sharma

Abstract:

Introduction: On the basis of available literature we know that various host factors play a role in outcome of Tuberculosis (TB) infection by modulating innate immunity. One such factor is Inducible Nitric Oxide Synthase enzyme (iNOS) which help in the production of Nitric Oxide (NO), an antimicrobial agent. Expression of iNOS is in control of various host factors in which Vitamin D along with its nuclear receptor Vitamin D receptor (VDR) is one of them. Vitamin D along with its receptor also produces cathelicidin (antimicrobicidal agent). With this background, we attempted to investigate the levels of Vitamin D and NO along with their associated molecules in tuberculosis patients and household contacts as compared to healthy controls and assess the implication of these findings in susceptibility to tuberculosis (TB). Study subjects and methods: 100 active TB patients, 75 household contacts, and 70 healthy controls were taken. VDR and iNOS mRNA levels were studied using real-time PCR. Serum VDR, cathelicidin, iNOS levels were measured using ELISA. Serum Vitamin D levels were measured in serum samples using chemiluminescence based immunoassay. NO was measured using colorimetry based kit. Results: VDR and iNOS mRNA levels were found to be lower in active TB group compared to household contacts and healthy controls (P=0.0001 and 0.005 respectively). The serum levels of Vitamin D were also found to be lower in active TB group as compared to healthy controls (P =0.001). Levels of cathelicidin and NO was higher in patient group as compared to other groups (p=0.01 and 0.5 respectively). However, the expression of VDR and iNOS and levels of vitamin D was significantly (P < 0.05) higher in household contacts compared to both active TB and healthy control groups. Inference: Higher levels of Vitamin D along with VDR and iNOS expression in household contacts as compared to patients suggest that vitamin D might have a protective role against TB which prevents activation of the disease. From our data, we can conclude that decreased vitamin D levels could be implicated in disease progression and we can use cathelicidin and NO as a biomarker for early diagnosis of pulmonary tuberculosis.

Keywords: vitamin D, VDR, iNOS, tuberculosis

Procedia PDF Downloads 277

Authors: Tony Jehi, Sujatha Rajaram, Nader majzoub, Joan Sabate

Abstract:

Aging significantly increases the incidence of various cardiometabolic diseases, including cardiovascular disease (CVD). To combat CVD and its associated risk factors, it is imperative to adopt a healthy dietary pattern that is rife with beneficial nutrient and non-nutrient compounds. Unsaturated fats, specifically n-3 polyunsaturated fatty acids (n-3 PUFA), have cardio-protective effects; the opposite is true for saturated fatty acids. What role, if any, does the biomarker of fatty acid intake (specific fatty acids in the erythrocyte) play in predicting cardiometabolic risk among the elderly, a population highly susceptible to increased mortality and morbidity from CVD risk factors, remains unclear. This was a secondary analysis of the Walnuts and Healthy Aging Study. Briefly, elderly (n=192, mean age 69 y) participants followed their usual diet and were randomized into two groups to either eat walnuts daily or abstain from eating walnuts for a period of 2 years. The purpose was to identify potential associations between erythrocyte membrane fatty acids and cardiometabolic risk factors (body weight, blood pressure, blood lipids, and fasting glucose). Erythrocyte n-3 PUFA were inversely associated with total cholesterol (ß = -3.83; p= 0.02), triglycerides (ß = -7.66; p= <0.01), and fasting glucose (ß = -0.19; p=0.03). Specifically, erythrocyte ALA (ß= -1.59; P = 0.04) and DPA (ß= -0.62; P=0.04) were inversely associated with diastolic blood pressure and fasting glucose, respectively. N-6 PUFAs were positively associated with systolic blood pressure (ß=1.10; P=0.02). Mono-unsaturated fatty acids were positively associated with TAG (ß = 4.16; P=0.03). Total saturated fatty acids were not associated with any cardiometabolic risk factors. No association was found between any erythrocyte fatty acid and body weight. In conclusion, erythrocyte n-3 PUFA may be used as a biomarker to predict the cardiometabolic risk among healthy elders, providing support for the American Heart Association guidelines for including n-3 PUFA for preventing CVD.

Keywords: cardiometabolic diseases, erythrocyte fatty acids, elderly, n-3 PUFA

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