Search results for: cardio phenotype
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 227

Search results for: cardio phenotype

167 The Impact of Artificial Intelligence on Autism Attitudes

Authors: Sara Asham Mahrous Kamel

Abstract:

A descriptive statistical analysis of the data showed that the most important factor evoking negative attitudes among teachers is student behavior. have been presented as useful models for understanding the risk factors and protective factors associated with the emergence of autistic traits. Although these "syndrome" forms of autism reach clinical thresholds, they appear to be distinctly different from the idiopathic or "non-syndrome" autism phenotype. Most teachers reported that kindergartens did not prepare them for the educational needs of children with autism, particularly in relation to non-verbal skills. The study is important and points the way for improving teacher inclusion education in Thailand. Inclusive education for students with autism is still in its infancy in Thailand. Although the number of autistic children in schools has increased significantly since the Thai government introduced the Education Regulations for Persons with Disabilities Act in 2008, there is a general lack of services for autistic students and their families. This quantitative study used the Teaching Skills and Readiness Scale for Students with Autism (APTSAS) to test the attitudes and readiness of 110 elementary school teachers when teaching students with autism in general education classrooms. To uncover the true nature of these co morbidities, it is necessary to expand the definition of autism to include the cognitive features of the disorder, and then apply this expanded conceptualization to examine patterns of autistic syndromes. This study used various established eye-tracking paradigms to assess the visual and attention performance of children with DS and FXS who meet the autism thresholds defined in the Social Communication Questionnaire. To study whether the autistic profiles of these children are associated with visual orientation difficulties ("sticky attention"), decreased social attention, and increased visual search performance, all of which are hallmarks of the idiopathic autistic child phenotype. Data will be collected from children with DS and FXS, aged 6 to 10 years, and two control groups matched for age and intellectual ability (i.e., children with idiopathic autism).In order to enable a comparison of visual attention profiles, cross-sectional analyzes of developmental trajectories are carried out. Significant differences in the visual-attentive processes underlying the presentation of autism in children with FXS and DS have been suggested, supporting the concept of syndrome specificity. The study provides insights into the complex heterogeneity associated with autism syndrome symptoms and autism itself, with clinical implications for the utility of autism intervention programs in DS and FXS populations.

Keywords: attitude, autism, teachers, sports activities, movement skills, motor skills

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166 The Impact of Technology and Artificial Intelligence on Children in Autism

Authors: Dina Moheb Rashid Michael

Abstract:

A descriptive statistical analysis of the data showed that the most important factor evoking negative attitudes among teachers is student behavior. have been presented as useful models for understanding the risk factors and protective factors associated with the emergence of autistic traits. Although these "syndrome" forms of autism reach clinical thresholds, they appear to be distinctly different from the idiopathic or "non-syndrome" autism phenotype. Most teachers reported that kindergartens did not prepare them for the educational needs of children with autism, particularly in relation to non-verbal skills. The study is important and points the way for improving teacher inclusion education in Thailand. Inclusive education for students with autism is still in its infancy in Thailand. Although the number of autistic children in schools has increased significantly since the Thai government introduced the Education Regulations for Persons with Disabilities Act in 2008, there is a general lack of services for autistic students and their families. This quantitative study used the Teaching Skills and Readiness Scale for Students with Autism (APTSAS) to test the attitudes and readiness of 110 elementary school teachers when teaching students with autism in general education classrooms. To uncover the true nature of these co morbidities, it is necessary to expand the definition of autism to include the cognitive features of the disorder, and then apply this expanded conceptualization to examine patterns of autistic syndromes. This study used various established eye-tracking paradigms to assess the visual and attention performance of children with DS and FXS who meet the autism thresholds defined in the Social Communication Questionnaire. To study whether the autistic profiles of these children are associated with visual orientation difficulties ("sticky attention"), decreased social attention, and increased visual search performance, all of which are hallmarks of the idiopathic autistic child phenotype. Data will be collected from children with DS and FXS, aged 6 to 10 years, and two control groups matched for age and intellectual ability (i.e., children with idiopathic autism).In order to enable a comparison of visual attention profiles, cross-sectional analyzes of developmental trajectories are carried out. Significant differences in the visual-attentive processes underlying the presentation of autism in children with FXS and DS have been suggested, supporting the concept of syndrome specificity. The study provides insights into the complex heterogeneity associated with autism syndrome symptoms and autism itself, with clinical implications for the utility of autism intervention programs in DS and FXS populations.

Keywords: attitude, autism, teachers, sports activities, movement skills, motor skills

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165 The Impact of Autism on Child's behavior and Attitude

Authors: Mariam Atef Zakaria Faltas

Abstract:

A descriptive statistical analysis of the data showed that the most important factor evoking negative attitudes among teachers is student behavior. have been presented as useful models for understanding the risk factors and protective factors associated with the emergence of autistic traits. Although these "syndrome" forms of autism reach clinical thresholds, they appear to be distinctly different from the idiopathic or "non-syndrome" autism phenotype. Most teachers reported that kindergartens did not prepare them for the educational needs of children with autism, particularly in relation to non-verbal skills. The study is important and points the way for improving teacher inclusion education in Thailand. Inclusive education for students with autism is still in its infancy in Thailand. Although the number of autistic children in schools has increased significantly since the Thai government introduced the Education Regulations for Persons with Disabilities Act in 2008, there is a general lack of services for autistic students and their families. This quantitative study used the Teaching Skills and Readiness Scale for Students with Autism (APTSAS) to test the attitudes and readiness of 110 elementary school teachers when teaching students with autism in general education classrooms. To uncover the true nature of these co morbidities, it is necessary to expand the definition of autism to include the cognitive features of the disorder, and then apply this expanded conceptualization to examine patterns of autistic syndromes. This study used various established eye-tracking paradigms to assess the visual and attention performance of children with DS and FXS who meet the autism thresholds defined in the Social Communication Questionnaire. To study whether the autistic profiles of these children are associated with visual orientation difficulties ("sticky attention"), decreased social attention, and increased visual search performance, all of which are hallmarks of the idiopathic autistic child phenotype. Data will be collected from children with DS and FXS, aged 6 to 10 years, and two control groups matched for age and intellectual ability (i.e., children with idiopathic autism).In order to enable a comparison of visual attention profiles, cross-sectional analyzes of developmental trajectories are carried out. Significant differences in the visual-attentive processes underlying the presentation of autism in children with FXS and DS have been suggested, supporting the concept of syndrome specificity. The study provides insights into the complex heterogeneity associated with autism syndrome symptoms and autism itself, with clinical implications for the utility of autism intervention programs in DS and FXS populations.

Keywords: attitude, autism, teachers, sports activities, movement skills, motor skills

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164 The Impact of Artificial Intelligence on Autism Attitudes and Laws

Authors: Randa Reda Luke Waheeb

Abstract:

A descriptive statistical analysis of the data showed that the most important factor evoking negative attitudes among teachers is student behavior. have been presented as useful models for understanding the risk factors and protective factors associated with the emergence of autistic traits. Although these "syndrome" forms of autism reach clinical thresholds, they appear to be distinctly different from the idiopathic or "non-syndrome" autism phenotype. Most teachers reported that kindergartens did not prepare them for the educational needs of children with autism, particularly in relation to non-verbal skills. The study is important and points the way for improving teacher inclusion education in Thailand. Inclusive education for students with autism is still in its infancy in Thailand. Although the number of autistic children in schools has increased significantly since the Thai government introduced the Education Regulations for Persons with Disabilities Act in 2008, there is a general lack of services for autistic students and their families. This quantitative study used the Teaching Skills and Readiness Scale for Students with Autism (APTSAS) to test the attitudes and readiness of 110 elementary school teachers when teaching students with autism in general education classrooms. To uncover the true nature of these co morbidities, it is necessary to expand the definition of autism to include the cognitive features of the disorder, and then apply this expanded conceptualization to examine patterns of autistic syndromes. This study used various established eye-tracking paradigms to assess the visual and attention performance of children with DS and FXS who meet the autism thresholds defined in the Social Communication Questionnaire. To study whether the autistic profiles of these children are associated with visual orientation difficulties ("sticky attention"), decreased social attention, and increased visual search performance, all of which are hallmarks of the idiopathic autistic child phenotype. Data will be collected from children with DS and FXS, aged 6 to 10 years, and two control groups matched for age and intellectual ability (i.e., children with idiopathic autism).In order to enable a comparison of visual attention profiles, cross-sectional analyzes of developmental trajectories are carried out. Significant differences in the visual-attentive processes underlying the presentation of autism in children with FXS and DS have been suggested, supporting the concept of syndrome specificity. The study provides insights into the complex heterogeneity associated with autism syndrome symptoms and autism itself, with clinical implications for the utility of autism intervention programs in DS and FXS populations.

Keywords: attitude, autism, teachers, sports activities, movement skills, motor skills

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163 The Impact of Artificial Intelligence on Autism Attitudes and Laws

Authors: Narges Arsanious Kamel Arsanious

Abstract:

A descriptive statistical analysis of the data showed that the most important factor evoking negative attitudes among teachers is student behavior. have been presented as useful models for understanding the risk factors and protective factors associated with the emergence of autistic traits. Although these "syndrome" forms of autism reach clinical thresholds, they appear to be distinctly different from the idiopathic or "non-syndrome" autism phenotype. Most teachers reported that kindergartens did not prepare them for the educational needs of children with autism, particularly in relation to non-verbal skills. The study is important and points the way for improving teacher inclusion education in Thailand. Inclusive education for students with autism is still in its infancy in Thailand. Although the number of autistic children in schools has increased significantly since the Thai government introduced the Education Regulations for Persons with Disabilities Act in 2008, there is a general lack of services for autistic students and their families. This quantitative study used the Teaching Skills and Readiness Scale for Students with Autism (APTSAS) to test the attitudes and readiness of 110 elementary school teachers when teaching students with autism in general education classrooms. To uncover the true nature of these co morbidities, it is necessary to expand the definition of autism to include the cognitive features of the disorder, and then apply this expanded conceptualization to examine patterns of autistic syndromes. This study used various established eye-tracking paradigms to assess the visual and attention performance of children with DS and FXS who meet the autism thresholds defined in the Social Communication Questionnaire. To study whether the autistic profiles of these children are associated with visual orientation difficulties ("sticky attention"), decreased social attention, and increased visual search performance, all of which are hallmarks of the idiopathic autistic child phenotype. Data will be collected from children with DS and FXS, aged 6 to 10 years, and two control groups matched for age and intellectual ability (i.e., children with idiopathic autism).In order to enable a comparison of visual attention profiles, cross-sectional analyzes of developmental trajectories are carried out. Significant differences in the visual-attentive processes underlying the presentation of autism in children with FXS and DS have been suggested, supporting the concept of syndrome specificity. The study provides insights into the complex heterogeneity associated with autism syndrome symptoms and autism itself, with clinical implications for the utility of autism intervention programs in DS and FXS populations.

Keywords: attitude, autism, teachers, sports activities, movement skills, motor skills

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162 Unveiling Comorbidities in Irritable Bowel Syndrome: A UK BioBank Study utilizing Supervised Machine Learning

Authors: Uswah Ahmad Khan, Muhammad Moazam Fraz, Humayoon Shafique Satti, Qasim Aziz

Abstract:

Approximately 10-14% of the global population experiences a functional disorder known as irritable bowel syndrome (IBS). The disorder is defined by persistent abdominal pain and an irregular bowel pattern. IBS significantly impairs work productivity and disrupts patients' daily lives and activities. Although IBS is widespread, there is still an incomplete understanding of its underlying pathophysiology. This study aims to help characterize the phenotype of IBS patients by differentiating the comorbidities found in IBS patients from those in non-IBS patients using machine learning algorithms. In this study, we extracted samples coding for IBS from the UK BioBank cohort and randomly selected patients without a code for IBS to create a total sample size of 18,000. We selected the codes for comorbidities of these cases from 2 years before and after their IBS diagnosis and compared them to the comorbidities in the non-IBS cohort. Machine learning models, including Decision Trees, Gradient Boosting, Support Vector Machine (SVM), AdaBoost, Logistic Regression, and XGBoost, were employed to assess their accuracy in predicting IBS. The most accurate model was then chosen to identify the features associated with IBS. In our case, we used XGBoost feature importance as a feature selection method. We applied different models to the top 10% of features, which numbered 50. Gradient Boosting, Logistic Regression and XGBoost algorithms yielded a diagnosis of IBS with an optimal accuracy of 71.08%, 71.427%, and 71.53%, respectively. Among the comorbidities most closely associated with IBS included gut diseases (Haemorrhoids, diverticular diseases), atopic conditions(asthma), and psychiatric comorbidities (depressive episodes or disorder, anxiety). This finding emphasizes the need for a comprehensive approach when evaluating the phenotype of IBS, suggesting the possibility of identifying new subsets of IBS rather than relying solely on the conventional classification based on stool type. Additionally, our study demonstrates the potential of machine learning algorithms in predicting the development of IBS based on comorbidities, which may enhance diagnosis and facilitate better management of modifiable risk factors for IBS. Further research is necessary to confirm our findings and establish cause and effect. Alternative feature selection methods and even larger and more diverse datasets may lead to more accurate classification models. Despite these limitations, our findings highlight the effectiveness of Logistic Regression and XGBoost in predicting IBS diagnosis.

Keywords: comorbidities, disease association, irritable bowel syndrome (IBS), predictive analytics

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161 Endocrine Therapy Resistance and Epithelial to Mesenchymal Transition Inhibits by INT3 & Quercetin in MCF7 Cell Lines

Authors: D. Pradhan, G. Tripathy, S. Pradhan

Abstract:

Objectives: Imperviousness gainst estrogen treatments is a noteworthy reason for infection backslide and mortality in estrogen receptor alpha (ERα)- positive breast diseases. Tamoxifen or estrogen withdrawal builds the reliance of breast malignancy cells on INT3 flagging. Here, we researched the commitment of Quercetin and INT3 motioning in endocrine-safe breast tumor cells. Methods: We utilized two models of endocrine treatments safe (ETR) breast tumor: Tamoxifen-safe (TamR) and long haul estrogen-denied (LTED) MCF7 cells. We assessed the transitory and intrusive limit of these cells by Transwell cells. Articulation of epithelial to mesenchymal move (EMT) controllers and in addition INT3 receptors and targets were assessed by constant PCR and western smudge investigation. Besides, we tried in-vitro hostile to Quercetin monoclonal Antibodies (mAbs) and Gamma Secretase Inhibitors (GSIs) as potential EMT inversion remedial specialists. At last, we created stable Quercetin overexpressing MCF7 cells and assessed their EMT components and reaction to Tamoxifen. Results: We found that ETR cells procured an Epithelial to Mesenchymal move (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we distinguished more elevated amount of INT3 however lower levels of INT1 and INT3 proposing a change to motioning through distinctive INT3 receptors after obtaining of resistance. Against Quercetin monoclonal antibodies and the GSI PF03084014 were powerful in obstructing the Quercetin/INT3 pivot and in part repressing the EMT process. As a consequence of this, cell relocation and attack were weakened and the immature microorganism like populace was essentially decreased. Hereditary hushing of Quercetin and INT3 prompted proportionate impacts. At long last, stable overexpression of Quercetin was adequate to make MCF7 lethargic to Tamoxifen by INT3 initiation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives intrusive conduct. Hostile to Quercetin mAbs and GSI PF03084014 lessen articulation of EMT particles decreasing cell obtrusiveness. Quercetin overexpression instigates Tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and INT3 warrants further clinical Correlation as substantial restorative methodologies in endocrine-safe breast.

Keywords: endocrine, epithelial, mesenchymal, INT3, quercetin, MCF7

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160 Quercetin and INT3 Inhibits Endocrine Therapy Resistance and Epithelial to Mesenchymal Transition in MCF7 Breast Cancer Cells

Authors: S. Pradhan, D. Pradhan, G. Tripathy

Abstract:

Anti-estrogen treatment resistant is a noteworthy reason for disease relapse and mortality in estrogen receptor alpha (ERα)- positive breast cancers. Tamoxifen or estrogen withdrawal increases the dependance of breast malignancy cells on INT3 signaling. Here, we researched the contribution of Quercetin and INT3 signaling in endocrine resistant breast cancer cells. Methods: We utilized two models of endocrine therapies resistant (ETR-) breast cancer: tamoxifen-resistant (TamR) and long term estrogen-deprived (LTED) MCF7 cells. We assessed the migratory and invasive limit of these cells by Transwell assay. Expression of epithelial to mesenchymal transition (EMT) controllers and in addition INT3 receptors and targets were assessed by real-time PCR and western blot analysis. Besides, we tried in vitro anti-Quercetin monoclonal antibodies (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal therapeutic agents. At last, we created stable Quercetin over expessing MCF7 cells and assessed their EMT features and response to tamoxifen. Results:We found that ETR cells acquired an epithelial to mesenchymal transition (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we detected higher level of INT3 however lower levels of INT31 and INT32 proposing a switch to targeting through distinctive INT3 receptors after obtaining of resistance. Anti-Quercetin monoclonal antibodies and the GSI PF03084014 were effective in obstructing the Quercetin/INT3 axis and in part inhibiting the EMT process. As a consequence of this, cell migration and invasion were weakened and the stem cell like population was considerably decreased. Genetic hushing of Quercetin and INT3 prompted proportionate impacts. Finally, stable overexpression of Quercetin was adequate to make MCF7 lethargic to tamoxifen by INT3 activation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives invasive conduct. Anti-Quercetin mAbs and GSI PF03084014 lessen expression of EMT molecules decreasing cellular invasiveness. Quercetin overexpression instigates tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and/or INT3 warrants further clinical assessment as substantial therapeutic methodologies in endocrine-resistant breast cancer.

Keywords: quercetin, INT3, mesenchymal transition, MCF7 breast cancer cells

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159 Critical Review whether Restricting Dietary Saturated Fat Can Reduce the Risk of Cardiovascular Disease

Authors: Obi Olor, Asu-nnandi Judith, Ishiekwen Bridget

Abstract:

Regardless of the settled perception that the substitution of saturated fats for starches or unsaturated fats builds low-density lipoprotein (LDL) cholesterol in people, in animal models, the relationship of saturated fat intake to the hazard of atherosclerotic cardiovascular ailment in people remains controversial. Clinical trials that supplanted immersed fat with polyunsaturated fat have, for the most part, demonstrated a lessening in CVD occasions, albeit a few reviews demonstrated no impacts. An autonomous relationship of soaked fat admission with CVD chance has not reliably appeared in planned epidemiologic reviews, albeit some have confirmed an expanded hazard in youthful people and in ladies. Substitution of soaked fat by polyunsaturated or monounsaturated fat reduces LDL and HDL cholesterol. Given the differing qualities of these cardio-protective eating methodologies and their healthy parts, one of the needs in research should be to attempt more near trials. These trials decide persistent worthiness, consequences for surrogate markers of hazard, and which at last affects morbidity and mortality.

Keywords: cardiovascular disease, dietary saturated fat, saturated fat, unsaturated fat

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158 Effectiveness of Simulation Resuscitation Training to Improve Self-Efficacy of Physicians and Nurses at Aga Khan University Hospital in Advanced Cardiac Life Support Courses Quasi-Experimental Study Design

Authors: Salima R. Rajwani, Tazeen Ali, Rubina Barolia, Yasmin Parpio, Nasreen Alwani, Salima B. Virani

Abstract:

Introduction: Nurses and physicians have a critical role in initiating lifesaving interventions during cardiac arrest. It is important that timely delivery of high quality Cardio Pulmonary Resuscitation (CPR) with advanced resuscitation skills and management of cardiac arrhythmias is a key dimension of code during cardiac arrest. It will decrease the chances of patient survival if the healthcare professionals are unable to initiate CPR timely. Moreover, traditional training will not prepare physicians and nurses at a competent level and their knowledge level declines over a period of time. In this regard, simulation training has been proven to be effective in promoting resuscitation skills. Simulation teaching learning strategy improves knowledge level, and skills performance during resuscitation through experiential learning without compromising patient safety in real clinical situations. The purpose of the study is to evaluate the effectiveness of simulation training in Advanced Cardiac Life Support Courses by using the selfefficacy tool. Methods: The study design is a quantitative research design and non-randomized quasi-experimental study design. The study examined the effectiveness of simulation through self-efficacy in two instructional methods; one is Medium Fidelity Simulation (MFS) and second is Traditional Training Method (TTM). The sample size was 220. Data was compiled by using the SPSS tool. The standardized simulation based training increases self-efficacy, knowledge, and skills and improves the management of patients in actual resuscitation. Results: 153 students participated in study; CG: n = 77 and EG: n = 77. The comparison was done between arms in pre and post-test. (F value was 1.69, p value is <0.195 and df was 1). There was no significant difference between arms in the pre and post-test. The interaction between arms was observed and there was no significant difference in interaction between arms in the pre and post-test. (F value was 0.298, p value is <0.586 and df is 1. However, the results showed self-efficacy scores were significantly higher within experimental group in post-test in advanced cardiac life support resuscitation courses as compared to Traditional Training Method (TTM) and had overall (p <0.0001) and F value was 143.316 (mean score was 45.01 and SD was 9.29) verses pre-test result showed (mean score was 31.15 and SD was 12.76) as compared to TTM in post-test (mean score was 29.68 and SD was 14.12) verses pre-test result showed (mean score was 42.33 and SD was 11.39). Conclusion: The standardized simulation-based training was conducted in the safe learning environment in Advanced Cardiac Life Suport Courses and physicians and nurses benefited from self-confidence, early identification of life-threatening scenarios, early initiation of CPR, and provides high-quality CPR, timely administration of medication and defibrillation, appropriate airway management, rhythm analysis and interpretation, and Return of Spontaneous Circulation (ROSC), team dynamics, debriefing, and teaching and learning strategies that will improve the patient survival in actual resuscitation.

Keywords: advanced cardiac life support, cardio pulmonary resuscitation, return of spontaneous circulation, simulation

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157 Precursor Muscle Cell’s Phenotype under Compression in a Biomimetic Mechanical Niche

Authors: Fatemeh Abbasi, Arne Hofemeier, Timo Betz

Abstract:

Muscle growth and regeneration critically depend on satellite cells (SCs) which are muscle stem cells located between the basal lamina and myofibres. Upon damage, SCs become activated, enter the cell cycle, and give rise to myoblasts that form new myofibres, while a sub-population self-renew and re-populate the muscle stem cell niche. In aged muscle as well as in certain muscle diseases such as muscular dystrophy, some of the SCs lose their regenerative ability. Although it is demonstrated that the chemical composition of SCs quiescent niche is different from the activated niche, the mechanism initially activated in the SCs remains unknown. While extensive research efforts focused on potential chemical activation, no such factor has been identified to the author’s best knowledge. However, it is substantiated that niche mechanics affects SCs behaviors, such as stemness and engraftment. We hypothesize that mechanical stress in the healthy niche (homeostasis) is different from the regenerative niche and that this difference could serve as an early signal activating SCs upon fiber damage. To investigate this hypothesis, we develop a biomimetic system to reconstitute both, the mechanical and the chemical environment of the SC niche. Cells will be confined between two elastic polyacrylamide (PAA) hydrogels with controlled elastic moduli and functionalized surface chemistry. By controlling the distance between the PAA hydrogel surfaces, we vary the compression forces exerted by the substrates on the cells, while the lateral displacement of the upper hydrogel will create controlled shear forces. To establish such a system, a simplified system is presented. We engineered a sandwich-like configuration of two elastic PAA layer with stiffnesses between 1 and 10 kPa and confined a precursor myoblast cell line (C2C12) in between these layers. Our initial observations in this sandwich model indicate that C2C12 cells show different behaviors under mechanical compression if compared to a control one-layer gel without compression. Interestingly, this behavior is stiffness-dependent. While the shape of C2C12 cells in the sandwich consisting of two stiff (10 kPa) layers was much more elongated, showing almost a neuronal phenotype, the cell shape in a sandwich situation consisting of one stiff and one soft (1 kPa) layer was more spherical. Surprisingly, even in proliferation medium and at very low cell density, the sandwich situation stimulated cell differentiation with increased striation and myofibre formation. Such behavior is commonly found for confluent cells in differentiation medium. These results suggest that mechanical changes in stiffness and applied pressure might be a relevant stimulation for changes in muscle cell behavior.

Keywords: C2C12 cells, compression, force, satellite cells, skeletal muscle

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156 Breast Cancer Therapy-Related Cardiac Dysfunction Identifying in Kazakhstan: Preliminary Findings of the Cohort Study

Authors: Saule Balmagambetova, Zhenisgul Tlegenova, Saule Madinova

Abstract:

Cardiotoxicity associated with anticancer treatment, now defined as cancer therapy-related cardiac dysfunction (CTRCD), accompanies cancer patients and negatively impacts their survivorship. Currently, a cardio-oncological service is being created in Kazakhstan based on the provisions of the European Society of Cardio-oncology (ESC) Guidelines. In the frames of a pilot project, a cohort study on CTRCD conditions was initiated at the Aktobe Cancer center. One hundred twenty-eight newly diagnosed breast cancer patients started on doxorubicin and/or trastuzumab were recruited. Echocardiography with global longitudinal strain (GLS) assessment, biomarkers panel (cardiac troponin (cTnI), brain natriuretic peptide (BNP), myeloperoxidase (MPO), galectin-3 (Gal-3), D-dimers, C-reactive protein (CRP)), and other tests were performed at baseline and every three months. Patients were stratified by the cardiovascular risks according to the ESC recommendations and allocated into the risk groups during the pre-treatment visit. Of them, 10 (7.8%) patients were assigned to the high-risk group, 48 (37.5%) to the medium-risk group, and 70 (54.7%) to the low-risk group, respectively. High-risk patients have been receiving their cardioprotective treatment from the outset. Patients were also divided by treatment - in the anthracycline-based 83 (64.8%), in trastuzumab- only 13 (10.2%), and in the mixed anthracycline/trastuzumab group 32 individuals (25%), respectively. Mild symptomatic CTRCD was revealed and treated in 2 (1.6%) participants, and a mild asymptomatic variant in 26 (20.5%). Mild asymptomatic conditions are defined as left ventricular ejection fraction (LVEF) ≥50% and further relative reduction in GLS by >15% from baseline and/or a further rise in cardiac biomarkers. The listed biomarkers were assessed longitudinally in repeated-measures linear regression models during 12 months of observation. The associations between changes in biomarkers and CTRCD and between changes in biomarkers and LVEF were evaluated. Analysis by risk groups revealed statistically significant differences in baseline LVEF scores (p 0.001), BNP (p 0.0075), and Gal-3 (p 0.0073). Treatment groups found no statistically significant differences at baseline. After 12 months of follow-up, only LVEF values showed a statistically significant difference by risk groups (p 0.0011). When assessing the temporal changes in the studied parameters for all treatment groups, there were statistically significant changes from visit to visit for LVEF (p 0.003); GLS (p 0.0001); BNP (p<0.00001); MPO (p<0.0001); and Gal-3 (p<0.0001). No moderate or strong correlations were found between the biomarkers values and LVEF, between biomarkers and GLS. Between the biomarkers themselves, a moderate, close to strong correlation was established between cTnI and D-dimer (r 0.65, p<0.05). The dose-dependent effect of anthracyclines has been confirmed: the summary dose has a moderate negative impact on GLS values: -r 0.31 for all treatment groups (p<0.05). The present study found myeloperoxidase as a promising biomarker of cardiac dysfunction in the mixed anthracycline/trastuzumab treatment group. The hazard of CTRCD increased by 24% (HR 1.21; 95% CI 1.01;1.73) per doubling in baseline MPO value (p 0.041). Increases in BNP were also associated with CTRCD (HR per doubling, 1.22; 95% CI 1.12;1.69). No cases of chemotherapy discontinuation due to cardiotoxic complications have been recorded. Further observations are needed to gain insight into the ability of biomarkers to predict CTRCD onset.

Keywords: breast cancer, chemotherapy, cardiotoxicity, Kazakhstan

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155 Heart Attack Prediction Using Several Machine Learning Methods

Authors: Suzan Anwar, Utkarsh Goyal

Abstract:

Heart rate (HR) is a predictor of cardiovascular, cerebrovascular, and all-cause mortality in the general population, as well as in patients with cardio and cerebrovascular diseases. Machine learning (ML) significantly improves the accuracy of cardiovascular risk prediction, increasing the number of patients identified who could benefit from preventive treatment while avoiding unnecessary treatment of others. This research examines relationship between the individual's various heart health inputs like age, sex, cp, trestbps, thalach, oldpeaketc, and the likelihood of developing heart disease. Machine learning techniques like logistic regression and decision tree, and Python are used. The results of testing and evaluating the model using the Heart Failure Prediction Dataset show the chance of a person having a heart disease with variable accuracy. Logistic regression has yielded an accuracy of 80.48% without data handling. With data handling (normalization, standardscaler), the logistic regression resulted in improved accuracy of 87.80%, decision tree 100%, random forest 100%, and SVM 100%.

Keywords: heart rate, machine learning, SVM, decision tree, logistic regression, random forest

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154 Computational Investigation on Structural and Functional Impact of Oncogenes and Tumor Suppressor Genes on Cancer

Authors: Abdoulie K. Ceesay

Abstract:

Within the sequence of the whole genome, it is known that 99.9% of the human genome is similar, whilst our difference lies in just 0.1%. Among these minor dissimilarities, the most common type of genetic variations that occurs in a population is SNP, which arises due to nucleotide substitution in a protein sequence that leads to protein destabilization, alteration in dynamics, and other physio-chemical properties’ distortions. While causing variations, they are equally responsible for our difference in the way we respond to a treatment or a disease, including various cancer types. There are two types of SNPs; synonymous single nucleotide polymorphism (sSNP) and non-synonymous single nucleotide polymorphism (nsSNP). sSNP occur in the gene coding region without causing a change in the encoded amino acid, while nsSNP is deleterious due to its replacement of a nucleotide residue in the gene sequence that results in a change in the encoded amino acid. Predicting the effects of cancer related nsSNPs on protein stability, function, and dynamics is important due to the significance of phenotype-genotype association of cancer. In this thesis, Data of 5 oncogenes (ONGs) (AKT1, ALK, ERBB2, KRAS, BRAF) and 5 tumor suppressor genes (TSGs) (ESR1, CASP8, TET2, PALB2, PTEN) were retrieved from ClinVar. Five common in silico tools; Polyphen, Provean, Mutation Assessor, Suspect, and FATHMM, were used to predict and categorize nsSNPs as deleterious, benign, or neutral. To understand the impact of each variation on the phenotype, Maestro, PremPS, Cupsat, and mCSM-NA in silico structural prediction tools were used. This study comprises of in-depth analysis of 10 cancer gene variants downloaded from Clinvar. Various analysis of the genes was conducted to derive a meaningful conclusion from the data. Research done indicated that pathogenic variants are more common among ONGs. Our research also shows that pathogenic and destabilizing variants are more common among ONGs than TSGs. Moreover, our data indicated that ALK(409) and BRAF(86) has higher benign count among ONGs; whilst among TSGs, PALB2(1308) and PTEN(318) genes have higher benign counts. Looking at the individual cancer genes predisposition or frequencies of causing cancer according to our research data, KRAS(76%), BRAF(55%), and ERBB2(36%) among ONGs; and PTEN(29%) and ESR1(17%) among TSGs have higher tendencies of causing cancer. Obtained results can shed light to the future research in order to pave new frontiers in cancer therapies.

Keywords: tumor suppressor genes (TSGs), oncogenes (ONGs), non synonymous single nucleotide polymorphism (nsSNP), single nucleotide polymorphism (SNP)

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153 Role of Lipid-Lowering Treatment in the Monocyte Phenotype and Chemokine Receptor Levels after Acute Myocardial Infarction

Authors: Carolina N. França, Jônatas B. do Amaral, Maria C.O. Izar, Ighor L. Teixeira, Francisco A. Fonseca

Abstract:

Introduction: Atherosclerosis is a progressive disease, characterized by lipid and fibrotic element deposition in large-caliber arteries. Conditions related to the development of atherosclerosis, as dyslipidemia, hypertension, diabetes, and smoking are associated with endothelial dysfunction. There is a frequent recurrence of cardiovascular outcomes after acute myocardial infarction and, at this sense, cycles of mobilization of monocyte subtypes (classical, intermediate and nonclassical) secondary to myocardial infarction may determine the colonization of atherosclerotic plaques in different stages of the development, contributing to early recurrence of ischemic events. The recruitment of different monocyte subsets during inflammatory process requires the expression of chemokine receptors CCR2, CCR5, and CX3CR1, to promote the migration of monocytes to the inflammatory site. The aim of this study was to evaluate the effect of lipid-lowering treatment by six months in the monocyte phenotype and chemokine receptor levels of patients after Acute Myocardial Infarction (AMI). Methods: This is a PROBE (prospective, randomized, open-label trial with blinded endpoints) study (ClinicalTrials.gov Identifier: NCT02428374). Adult patients (n=147) of both genders, ageing 18-75 years, were randomized in a 2x2 factorial design for treatment with rosuvastatin 20 mg/day or simvastatin 40 mg/day plus ezetimibe 10 mg/day as well as ticagrelor 90 mg 2x/day and clopidogrel 75 mg, in addition to conventional AMI therapy. Blood samples were collected at baseline, after one month and six months of treatment. Monocyte subtypes (classical - inflammatory, intermediate - phagocytic and nonclassical – anti-inflammatory) were identified, quantified and characterized by flow cytometry, as well as the expressions of the chemokine receptors (CCR2, CCR5 and CX3CR1) were also evaluated in the mononuclear cells. Results: After six months of treatment, there was an increase in the percentage of classical monocytes and reduction in the nonclassical monocytes (p=0.038 and p < 0.0001 Friedman Test), without differences for intermediate monocytes. Besides, classical monocytes had higher expressions of CCR5 and CX3CR1 after treatment, without differences related to CCR2 (p < 0.0001 for CCR5 and CX3CR1; p=0.175 for CCR2). Intermediate monocytes had higher expressions of CCR5 and CX3CR1 and lower expression of CCR2 (p = 0.003; p < 0.0001 and p = 0.011, respectively). Nonclassical monocytes had lower expressions of CCR2 and CCR5, without differences for CX3CR1 (p < 0.0001; p = 0.009 and p = 0.138, respectively). There were no differences after the comparison between the four treatment arms. Conclusion: The data suggest a time-dependent modulation of classical and nonclassical monocytes and chemokine receptor levels. The higher percentage of classical monocytes (inflammatory cells) suggest a residual inflammatory risk, even under preconized treatments to AMI. Indeed, these changes do not seem to be affected by choice of the lipid-lowering strategy.

Keywords: acute myocardial infarction, chemokine receptors, lipid-lowering treatment, monocyte subtypes

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152 Sudden Death of a Cocaine Body Packer: An Autopsy Examination Findings

Authors: Parthasarathi Pramanik

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Body packing is a way of transfer drugs across the international border or any drug prohibited area. The drugs are usually hidden in body packets inside the anatomical body cavities like mouth, intestines, rectum, ear, vagina etc. Cocaine is a very common drug for body packing across the world. A 48 year old male was reported dead in his hotel after complaining of chest pain and vomiting. At autopsy, there were eighty-two white cylindrical body packs in the stomach, small and large intestines. Seals of few of the packets were opened. Toxicological examination revealed presence of cocaine in the stomach, liver, kidney and hair samples. Microscopically, presence of myocardial necrosis with interstitial oedema along with hypertrophy and fibrosis of the myocardial fibre suggested heart failure due to cocaine cardio toxicity. However, focal lymphocyte infiltration and perivascular fibrosis in the myocardium also indicated chronic cocaine toxicity of the deceased. After careful autopsy examination it was considered the victim was died due congestive heart failure secondary to acute and chronic cocaine poisoning.

Keywords: cardiac failure, cocaine, body packer, sudden death

Procedia PDF Downloads 293
151 Genome-Wide Homozygosity Analysis of the Longevous Phenotype in the Amish Population

Authors: Sandra Smieszek, Jonathan Haines

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Introduction: Numerous research efforts have focused on searching for ‘longevity genes’. However, attempting to decipher the genetic component of the longevous phenotype have resulted in limited success and the mechanisms governing longevity remain to be explained. We conducted a genome-wide homozygosity analysis (GWHA) of the founder population of the Amish community in central Ohio. While genome-wide association studies using unrelated individuals have revealed many interesting longevity associated variants, these variants are typically of small effect and cannot explain the observed patterns of heritability for this complex trait. The Amish provide a large cohort of extended kinships allowing for in depth analysis via family-based approach excellent population due to its. Heritability of longevity increases with age with significant genetic contribution being seen in individuals living beyond 60 years of age. In our present analysis we show that the heritability of longevity is estimated to be increasing with age particularly on the paternal side. Methods: The present analysis integrated both phenotypic and genotypic data and led to the discovery of a series of variants, distinct for stratified populations across ages and distinct for paternal and maternal cohorts. Specifically 5437 subjects were analyzed and a subset of 893 successfully genotyped individuals was used to assess CHIP heritability. We have conducted the homozygosity analysis to examine if homozygosity is associated with increased risk of living beyond 90. We analyzed AMISH cohort genotyped for 614,957 SNPs. Results: We delineated 10 significant regions of homozygosity (ROH) specific for the age group of interest (>90). Of particular interest was ROH on chromosome 13, P < 0.0001. The lead SNPs rs7318486 and rs9645914 point to COL4A2 and our lead SNP. COL25A1 encodes one of the six subunits of type IV collagen, the C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth. COL4A2 mutations have been reported with a broader spectrum of cerebrovascular, renal, ophthalmological, cardiac, and muscular abnormalities. The second region of interest points to IRS2. Furthermore we built a classifier using the obtained SNPs from the significant ROH region with 0.945 AUC giving ability to discriminate between those living beyond to 90 years of age and beyond. Conclusion: In conclusion our results suggest that a history of longevity does indeed contribute to increasing the odds of individual longevity. Preliminary results are consistent with conjecture that heritability of longevity is substantial when we start looking at oldest fifth and smaller percentiles of survival specifically in males. We will validate all the candidate variants in independent cohorts of centenarians, to test whether they are robustly associated with human longevity. The identified regions of interest via ROH analysis could be of profound importance for the understanding of genetic underpinnings of longevity.

Keywords: regions of homozygosity, longevity, SNP, Amish

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150 Grape Seed Extract and Zinc Containing Multivitamin-Mineral Nutritional Food Supplement Protects Heart against Myocardial Ischemic-Reperfusion Injury in Wistar Rats

Authors: S. M. Satyam, K. L. Bairy, R. Pirasanthan, R. L. Vaishnav

Abstract:

Zincovit tablets have been used as nutritional food supplement over a prolonged period of time. The aim of the present study was to investigate the cardio-protective effect of combined formulation of grape seed extract and Zincovit tablets (40, 80 and 160 mg/kg) using a Langendorff model of ischemia-reperfusion in Wistar rats. Following 21 days of pre-treatment, combined formulation of grape seed extract and Zincovit tablets significantly attenuated ischemia-reperfusion induced cardiac injury in terms of increased coronary flow rate (p < 0.01), decreased creatine kinase activity in coronary effluent (p < 0.05), decreased MDA (p < 0.001), 4-HNE (p < 0.001) and increased protein thiol content (p < 0.01) in comparison with the untreated (control) group. This study opens an avenue to clinical studies to demonstrate the validity of this paradigm as a nutritional food supplement, which could improve the clinical outcome of patients subjected to percutaneous angioplasty.

Keywords: grape seed extract, myocardial ischemia-reperfusion injury, oxidative stress, Zincovit tablets

Procedia PDF Downloads 349
149 DeepOmics: Deep Learning for Understanding Genome Functioning and the Underlying Genetic Causes of Disease

Authors: Vishnu Pratap Singh Kirar, Madhuri Saxena

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Advancement in sequence data generation technologies is churning out voluminous omics data and posing a massive challenge to annotate the biological functional features. With so much data available, the use of machine learning methods and tools to make novel inferences has become obvious. Machine learning methods have been successfully applied to a lot of disciplines, including computational biology and bioinformatics. Researchers in computational biology are interested to develop novel machine learning frameworks to classify the huge amounts of biological data. In this proposal, it plan to employ novel machine learning approaches to aid the understanding of how apparently innocuous mutations (in intergenic DNA and at synonymous sites) cause diseases. We are also interested in discovering novel functional sites in the genome and mutations in which can affect a phenotype of interest.

Keywords: genome wide association studies (GWAS), next generation sequencing (NGS), deep learning, omics

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148 Patterns of Libido, Sexual Activity and Sexual Performance in Female Migraineurs

Authors: John Farr Rothrock

Abstract:

Although migraine traditionally has been assumed to convey a relative decrease in libido, sexual activity and sexual performance, recent data have suggested that the female migraine population is far from homogenous in this regard. We sought to determine the levels of libido, sexual activity and sexual performance in the female migraine patient population both generally and according to clinical phenotype. In this single-blind study, a consecutive series of sexually active new female patients ages 25-55 initially presenting to a university-based headache clinic and having a >1 year history of migraine were asked to complete anonymously a survey assessing their sexual histories generally and as they related to their headache disorder and the 19-item Female Sexual Function Index (FSFI). To serve as 2 separate control groups, 100 sexually active females with no history of migraine and 100 female migraineurs from the general (non-clinic) population but matched for age, marital status, educational background and socioeconomic status completed a similar survey. Over a period of 3 months, 188 consecutive migraine patients were invited to participate. Twenty declined, and 28 of the remaining 160 potential subjects failed to meet the inclusion criterion utilized for “sexually active” (ie, heterosexual intercourse at a frequency of > once per month in each of the preceding 6 months). In all groups younger age (p<.005), higher educational level attained (p<.05) and higher socioeconomic status (p<.025) correlated with a higher monthly frequency of intercourse and a higher likelihood of intercourse resulting in orgasm. Relative to the 100 control subjects with no history of migraine, the two migraine groups (total n=232) reported a lower monthly frequency of intercourse and recorded a lower FSFI score (both p<.025), but the contribution to this difference came primarily from the chronic migraine (CM) subgroup (n=92). Patients with low frequency episodic migraine (LFEM) and mid frequency episodic migraine (MFEM) reported a higher FSFI score, higher monthly frequency of intercourse, higher likelihood of intercourse resulting in orgasm and higher likelihood of multiple active sex partners than controls. All migraine subgroups reported a decreased likelihood of engaging in intercourse during an active migraine attack, but relative to the CM subgroup (8/92=9%), a higher proportion of patients in the LFEM (12/49=25%), MFEM (14/67=21%) and high frequency episodic migraine (HFEM: 6/14=43%) subgroups reported utilizing intercourse - and orgasm specifically - as a means of potentially terminating a migraine attack. In the clinic vs no-clinic groups there were no significant differences in the dependent variables assessed. Research subjects with LFEM and MFEM may report a level of libido, frequency of intercourse and likelihood of orgasm-associated intercourse that exceeds what is reported by age-matched controls free of migraine. Many patients with LFEM, MFEM and HFEM appear to utilize intercourse/orgasm as a means to potentially terminate an acute migraine attack.

Keywords: migraine, female, libido, sexual activity, phenotype

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147 The Molecular Biology Behind the Spread of Breast Cancer Inflammatory Breast Cancer: Symptoms and Genetic Factors

Authors: Fakhrosadat Sajjadian

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In the USA, about 5% of women diagnosed with breast cancer annually are affected by Inflammatory Breast Cancer (IBC), which is a highly aggressive type of Locally Advanced Breast Cancer (LABC). It is a type of LABC that is clinically and pathologically different, known for its rapid growth, invasiveness, and ability to promote the growth of blood vessels. Almost all women are found to have lymph nodes affected upon diagnosis, while around 36% show obvious distant metastases. Even with the latest improvements in multimodality therapies, the outlook for patients with IBC remains bleak, as the average disease-free survival time is less than 2.5 years. Recent research on the genetic factors responsible for the IBC phenotype has resulted in the discovery of genes that play a role in the advancement of this illness. The development of primary human cell lines and animal models has assisted in this research. These advancements offer new possibilities for future actions in identifying and treating IBC.

Keywords: breast cancer, inflammation, diagnosis, IBC, LABC

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146 Effects of Oxidized LDL in M2 Macrophages: Implications in Atherosclerosis

Authors: Fernanda Gonçalves, Karla Alcântara, Vanessa Moura, Patrícia Nolasco, Jorge Kalil, Maristela Hernandez

Abstract:

Introduction: Atherosclerosis is a chronic disease where two striking features are observed: retention of lipids and inflammation. Understanding the interaction between immune cells and lipoproteins involved in atherogenesis are urgent challenges, since cardiovascular diseases are the leading cause of death worldwide. Macrophages are critical to the development of atherosclerotic plaques and in the perpetuation of inflammation in these lesions. These cells are also directly involved in unstable plaque rupture. Recently different populations of macrophages are being identified in atherosclerotic lesions. Although the presence of M2 macrophages (macrophages activated by the alternative pathway, eg. The IL-4) has been identified, the function of these cells in atherosclerosis is not yet defined. M2 macrophages have a high endocytic capacity, they promote remodeling of tissues and to have anti-inflammatory activity. However, in atherosclerosis, especially unstable plaques, severe inflammatory reaction, accumulation of cellular debris and intense degradation of the tissue is observed. Thus, it is possible that the M2 macrophages have altered function (phenotype) in atherosclerosis. Objective: Our aim is to evaluate if the presence of oxidized LDL alters the phenotype and function of M2 macrophages in vitro. Methods: For this, we will evaluate whether the addition of lipoprotein in M2 macrophages differentiated in vitro with IL -4 induces 1) a reduction in the secretion of anti-inflammatory cytokines (CBA and ELISA), 2) secretion of inflammatory cytokines (CBA and ELISA), 3) expression of cell activation markers (Flow cytometry), 4) alteration in gene expression of molecules adhesion and extracellular matrix (Real-Time PCR) and 5) Matrix degradation (confocal microscopy). Results: In oxLDL stimulated M2 macrophages cultures we did not find any differences in the expression of the cell surface markers tested, including: HLA-DR, CD80, CD86, CD206, CD163 and CD36. Also, cultures stimulated with oxLDL had similar phagocytic capacity when compared to unstimulated cells. However, in the supernatant of these cultures an increase in the secretion of the pro-inflammatory cytokine IL-8 was detected. No significant changes where observed in IL-6, IL-10, IL-12 and IL-1b levels. The culture supernatant also induced massive extracellular matrix (produced by mouse embryo fibroblast) filaments degradation. When evaluating the expression of 84 extracellular matrix and adhesion molecules genes, we observed that the stimulation of oxLDL in M2 macrophages decreased 47% of the genes and increased the expression of only 3% of the genes. In particular we noted that oxLDL inhibit the expression of 60% of the genes constituents of extracellular matrix and collagen expressed by these cells, including fibronectin1 and collagen VI. We also observed a decrease in the expression of matrix protease inhibitors, such as TIMP 2. On the opposite, the matricellular protein thrombospondin had a 12 fold increase in gene expression. In the presence of native LDL 90% of the genes had no altered expression. Conclusion: M2 macrophages stimulated with oxLDL secrete the pro-inflammatory cytokine IL-8, have an altered extracellular matrix constituents gene expression, and promote the degradation of extracellular matrix. M2 macrophages may contribute to the perpetuation of inflammation in atherosclerosis and to plaque rupture.

Keywords: atherosclerosis, LDL, macrophages, m2

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145 Sex Differences in Age-Related AMPK-Sirt1 Axis Alteration in Human Heart

Authors: Maria Luisa Barcena De Arellano, Sofya Pozdniakova, Pavelas Karkacas, Anja Kuhl, Istvan Baczko, Yury Ladilov, Vera Regitz-Zagrosek

Abstract:

Introduction: Aging is associated with deterioration of the physiological function, leading to systemic inflammation and mitochondrial dysfunction that promote the development of cardiovascular diseases. Sex differences in aging-related cardiovascular diseases have been postulated. However, their precise mechanisms remain unclear. In the current study, we aimed to investigate the sex difference in the age-related alteration in Sirt1-AMPK signaling and its relation to the mitochondrial biogenesis and inflammation. Methods: Male and female human non-disease lateral left ventricular wall tissue (young (17–40 years; n= 7 male and 7 female) and old (50–68 years; n= 9 male and 8 female)) were used. qRT-PCR, western blot and immunohistochemistry assays were performed for expression analyses of Sirt1, AMPK, pAMPK, ac-Ku70, TFAM, PGC-1α, Sirt3, SOD2 and catalase. CD68 was used as a marker for macrophages and the ratio of IL-12:IL10 (pro-inflammatory phenotype (high IL-12/low IL-10) and anti-inflammatory phenotype (low IL-12/high IL-10) was used to examine the inflammatory stage in the heart. Results: Sirt1 expression was significantly higher in young females compared to young males, whereas in aged hearts Sirt1 expression was significantly downregulated in females, but not in males. In line with the Sirt1 downregulation in aged females, acetylation of nuclear Ku70, a direct target of Sirt1, in aged female hearts was significantly elevated. The activity of AMPK was significantly decreased in aged individuals, however no sex differences in the AMPK expression or activity were found in young or old individuals. The expression of mitochondrial proteins TOM40, SOD2 and Sirt3 was significantly higher in young females compared to young males, while in aged female hearts SOD2 and TOM40 were downregulated. In addition, the expression of catalase, a key cytosolic and mitochondrial anti-oxidative enzyme was significantly higher in young females and this female sex benefit was lost in aged hearts. In addition, the number of cardiac macrophages was significantly increased in old female, but not in male hearts. Consistently, the pro-inflammatory shift in old females was further confirmed by differences in the IL12/IL10 ratio in young female cardiac tissue in a favour of the anti-inflammatory mediator IL-10 (ratio 1:4) compared to young males (ratio 1:1). The anti-inflammatory environment in the heart was lost in aged females (ratio 1:1). Conclusion: Aging leads to the significant downregulation of Sirt1 expression and elevated acetylation of Ku70 in female, but not in male hearts. Furthermore, a beneficial upregulation of mitochondrial and anti-oxidative proteins in young females is lost with aging. Moreover, the malfunctions in the expression of Sirt1 and mitochondrial proteins in aged female hearts is accompanied by a significant pro-inflammatory shift. The study provides a molecular basis for the increased incidence of cardiovascular diseases in old women.

Keywords: inflammation, mitochondrial dysfunction, aging, Sirt1-AMPK axis

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144 The Use of Emergency Coronary Angiography in Patients Following Out-Of-Hospital Cardiac Arrest and Subsequent Cardio-Pulmonary Resuscitation

Authors: Scott Ashby, Emily Granger, Mark Connellan

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Objectives: 1) To identify if emergency coronary angiography improves outcomes in studies examining OHCA from assumed cardiac aetiology? 2) If so, is it indicated in all patients resuscitated following OHCA, and if not, who is it indicated for? 3) How effective are investigations for screening for the appropriate patients? Background: Out-of-hospital cardiac arrest is one of the leading mechanisms of death, and the most common causative pathology is coronary artery disease. In-hospital treatment following resuscitation greatly affects outcomes, yet there is debate over the most effective protocol. Methods: A literature search was conducted over multiple databases to identify all relevant articles published from 2005. An inclusion criterion was applied to all publications retrieved, which were then sorted by type. Results: A total of 3 existing reviews and 29 clinical studies were analysed in this review. There were conflicting conclusions, however increased use of angiography has shown to improve outcomes in the majority of studies, which cover a variety of settings and cohorts. Recommendations: Currently, emergency coronary angiography appears to improve outcomes in all/most cases of OHCA of assumed cardiac aetiology, regardless of ECG findings. Until a better tool for screening is available to reduce unnecessary procedures, the benefits appear to outweigh the costs/risks.

Keywords: out of hospital cardiac arrest, coronary angiography, resuscitation, emergency medicine

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143 Prevalence and Molecular Characterization of Extended-Spectrum–β Lactamase and Carbapenemase-Producing Enterobacterales from Tunisian Seafood

Authors: Mehdi Soula, Yosra Mani, Estelle Saras, Antoine Drapeau, Raoudha Grami, Mahjoub Aouni, Jean-Yves Madec, Marisa Haenni, Wejdene Mansour

Abstract:

Multi-resistance to antibiotics in gram-negative bacilli and particularly in enterobacteriaceae, has become frequent in hospitals in Tunisia. However, data on antibiotic resistant bacteria in aquatic products are scarce. The aims of this study are to estimate the proportion of ESBL- and carbapenemase-producing Enterobacterales in seafood (clams and fish) in Tunisia and to molecularly characterize the collected isolates. Two types of seafood were sampled in unrelated markets in four different regions in Tunisia (641 pieces of farmed fish and 1075 mediterranean clams divided into 215 pools, and each pool contained 5 pieces). Once purchased, all samples were incubated in tubes containing peptone salt broth for 24 to 48h at 37°C. After incubation, overnight cultures were isolated on selective MacConkey agar plates supplemented with either imipenem or cefotaxime, identified using API20E test strips (bioMérieux, Marcy-l’Étoile, France) and confirmed by Maldi-TOF MS. Antimicrobial susceptibility was determined by the disk diffusion method on Mueller-Hinton agar plates and results were interpreted according to CA-SFM 2021. ESBL-producing Enterobacterales were detected using the Double Disc Synergy Test (DDST). Carbapenem-resistance was detected using an ertapenem disk and was respectively confirmed using the ROSCO KPC/MBL and OXA-48 Confirm Kit (ROSCO Diagnostica, Taastrup, Denmark). DNA was extracted using a NucleoSpin Microbial DNA extraction kit (Macherey-Nagel, Hoerdt, France), according to the manufacturer’s instructions. Resistance genes were determined using the CGE online tools. The replicon content and plasmid formula were identified from the WGS data using PlasmidFinder 2.0.1 and pMLST 2.0. From farmed fishes, nine ESBL-producing strains (9/641, 1.4%) were isolated, which were identified as E. coli (n=6) and K. pneumoniae (n=3). Among the 215 pools of 5 clams analyzed, 18 ESBL-producing isolates were identified, including 14 E. coli and 4 K. pneumoniae. A low isolation rate of ESBL-producing Enterobacterales was detected 1.6% (18/1075) in clam pools. In fish, the ESBL phenotype was due to the presence of the blaCTX-M-15 gene in all nine isolates, but no carbapenemase gene was identified. In clams, the predominant ESBL phenotype was blaCTX-M-1 (n=6/18). blaCPE (NDM1, OXA48) was detected only in 3 isolates ‘K. pneumoniae isolates’. Replicon typing on the strains carring the ESBL and carbapenemase gene revelead that the major type plasmid carried ESBL were IncF (42.3%) [n=11/26]. In all, our results suggest that seafood can be a reservoir of multi-drug resistant bacteria, most probably of human origin but also by the selection pressure of antibiotic. Our findings raise concerns that seafood bought for consumption may serve as potential reservoirs of AMR genes and pose serious threat to public health.

Keywords: BLSE, carbapenemase, enterobacterales, tunisian seafood

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142 Conception of a Regulated, Dynamic and Intelligent Sewerage in Ostrevent

Authors: Rabaa Tlili Yaakoubi, Hind Nakouri, Olivier Blanpain

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The current tools for real time management of sewer systems are based on two software tools: the software of weather forecast and the software of hydraulic simulation. The use of the first ones is an important cause of imprecision and uncertainty, the use of the second requires temporal important steps of decision because of their need in times of calculation. This way of proceeding fact that the obtained results are generally different from those waited. The major idea of the CARDIO project is to change the basic paradigm by approaching the problem by the "automatic" face rather than by that "hydrology". The objective is to make possible the realization of a large number of simulations at very short times (a few seconds) allowing to take place weather forecasts by using directly the real time meditative pluviometric data. The aim is to reach a system where the decision-making is realized from reliable data and where the correction of the error is permanent. A first model of control laws was realized and tested with different return-period rainfalls. The gains obtained in rejecting volume vary from 40 to 100%. The development of a new algorithm was then used to optimize calculation time and thus to overcome the subsequent combinatorial problem in our first approach. Finally, this new algorithm was tested with 16- year-rainfall series. The obtained gains are 60% of total volume rejected to the natural environment and of 80 % in the number of discharges.

Keywords: RTC, paradigm, optimization, automation

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141 Evaluating Models Through Feature Selection Methods Using Data Driven Approach

Authors: Shital Patil, Surendra Bhosale

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Cardiac diseases are the leading causes of mortality and morbidity in the world, from recent few decades accounting for a large number of deaths have emerged as the most life-threatening disorder globally. Machine learning and Artificial intelligence have been playing key role in predicting the heart diseases. A relevant set of feature can be very helpful in predicting the disease accurately. In this study, we proposed a comparative analysis of 4 different features selection methods and evaluated their performance with both raw (Unbalanced dataset) and sampled (Balanced) dataset. The publicly available Z-Alizadeh Sani dataset have been used for this study. Four feature selection methods: Data Analysis, minimum Redundancy maximum Relevance (mRMR), Recursive Feature Elimination (RFE), Chi-squared are used in this study. These methods are tested with 8 different classification models to get the best accuracy possible. Using balanced and unbalanced dataset, the study shows promising results in terms of various performance metrics in accurately predicting heart disease. Experimental results obtained by the proposed method with the raw data obtains maximum AUC of 100%, maximum F1 score of 94%, maximum Recall of 98%, maximum Precision of 93%. While with the balanced dataset obtained results are, maximum AUC of 100%, F1-score 95%, maximum Recall of 95%, maximum Precision of 97%.

Keywords: cardio vascular diseases, machine learning, feature selection, SMOTE

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140 Hydrogel Based on Cellulose Acetate Used as Scaffold for Cell Growth

Authors: A. Maria G. Melero, A. M. Senna, J. A. Domingues, M. A. Hausen, E. Aparecida R. Duek, V. R. Botaro

Abstract:

A hydrogel from cellulose acetate cross linked with ethylenediaminetetraacetic dianhydride (HAC-EDTA) was synthesized by our research group, and submitted to characterization and biological tests. Cytocompatibility analysis was performed by confocal microscopy using human adipocyte derived stem cells (ASCs). The FTIR analysis showed characteristic bands of cellulose acetate and hydroxyl groups and the tensile tests evidence that HAC-EDTA present a Young’s modulus of 643.7 MPa. The confocal analysis revealed that there was cell growth at the surface of HAC-EDTA. After one day of culture the cells presented spherical morphology, which may be caused by stress of the sequestration of Ca2+ and Mg2+ ions at the cell medium by HAC-EDTA, as demonstrated by ICP-MS. However, after seven days and 14 days of culture, the cells present fibroblastoid morphology, phenotype expected by this cellular type. The results give efforts to indicate this new material as a potential biomaterial for tissue engineering, in the future in vivo approach.

Keywords: cellulose acetate, hydrogel, biomaterial, cellular growth

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139 Teaching Basic Life Support in More Than 1000 Young School Children in 5th Grade

Authors: H. Booke, R. Nordmeier

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Sudden cardiac arrest is sometimes eye-witnessed by kids. Mostly, their (grand-)parents are affected by sudden cardiac arrest, putting these kids under enormous psychological pressure: Although they are more than desperate to help, they feel insecure and helpless and are afraid of causing harm rather than realizing their chance to help. Even years later, they may blame themselves for not having helped their beloved ones. However, the absolute majority of school children - at least in Germany - is not educated to provide first aid. Teaching young kids (5th grade) in basic life support thus may help to save lives while washing away the kids' fear from causing harm during cardio-pulmonary resuscitation. A teaching of circulatory and respiratory (patho-)physiology, followed by hands-on training of basic life support for every single child, was offered to each school in our district. The teaching was performed by anesthesiologists, and the program was called 'kids can save lives'. However, before enrollment in this program, the entire class must have had lessons in biology with a special focus on heart and circulation as well as lung and gas exchange. More than 1.000 kids were taught and trained in basic life support, giving them the knowledge and skills to provide basic life support. This may help to reduce the rate of failure to provide first aid. Therefore, educating young kids in basic life support may not only help to save lives, but it also may help to prevent any feelings of guilt because of not having helped in cases of eye-witnessed sudden cardiac arrest.

Keywords: teaching, children, basic life support, cardiac arrest, CPR

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138 Mechanical Environment of the Aortic Valve and Mechanobiology

Authors: Rania Abdulkareem Aboubakr Mahdaly Ammar

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The aortic valve (AV) is a complex mechanical environment that includes flexure, tension, pressure and shear stress forces to blood flow during cardiac cycle. This mechanical environment regulates AV tissue structure by constantly renewing and remodeling the phenotype. In vitro, ex vivo and in vivo studies have explained that pathological states such as hypertension and congenital defects like bicuspid AV ( BAV ) can potentially alter the AV’s mechanical environment, triggering a cascade of remodeling, inflammation and calcification activities in AV tissue. Changes in mechanical environments are first sent by the endothelium that induces changes in the extracellular matrix, and triggers cell differentiation and activation. However, the molecular mechanism of this process is not very well understood. Understanding these mechanisms is critical for the development of effective medical based therapies. Recently, there have been some interesting studies on characterizing the hemodynamics associated with AV, especially in pathologies like BAV, using different experimental and numerical methods. Here, we review the current knowledge of the local AV mechanical environment and its effect on valve biology, focusing on in vitro and ex vivo approaches.

Keywords: aortic valve mechanobiology, bicuspid calcification, pressure stretch, shear stress

Procedia PDF Downloads 337