Search results for: newcastle disease
3397 Access of Refugees in Rural Areas to Regular Medication during COVID-19 Era: International Organization for Migration, Jordan Experience
Authors: Rasha Shoumar
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Background: Since the onset of the Syria crisis in 2011, Jordan has hosted many Syrian refugees, many of which are residing in urban and rural areas. Vulnerability of refugees has increased due to the COVID-19 pandemic, adding to their already existing challenge in access to medical services, rendering them vulnerable to the complications of untreated medical conditions and amplifying their risk for severe COVID-19 disease. To improve health outcomes and access to health care services in a COVID-19 context, IOM (The International Organization for Migration) provided health services including awareness raising, direct primary health care through mobile teams and referrals to secondary services were extended to the vulnerable populations of refugees. Method: 6 community health volunteers were trained and deployed to different governorates to provide COVID-19 and non-communicable disease awareness and collect data rated to non-communicable disease and access to medical health services. Primary health care services were extended to 7 governorates through a mobile medical team, providing medical management. The collected Data was reviewed and analyzed. Results: 2150 refugees in rural areas were reached out by community health volunteers, out of which 78 received their medications through the Ministry of Health, 121 received their medications through different non-governmental organizations, 665 patients couldn’t afford buying any medications, 1286 patients were occasionally buying their medications when they were able to afford it. 853 patients received medications and follow up through IOM mobile clinics, the most common conditions were hypertension, diabetes, hyperlipidemia, anemia, heart disease, thyroid disease, asthma, seizures, and psychiatric conditions. 709 of these patients had more than 3 of the comorbidities. Multiple cases were referred for secondary and tertiary lifesaving interventions. Conclusion: Non communicable diseases are highly prevalent among refugee population in Jordan, access to medical services have proven to be a challenge in rural areas especially during the COVID-19 era, many of the patients have multiple uncontrolled medical conditions placing them at risk for complications and risk for severe COVID-19 disease. Deployment of mobile clinics to rural areas plays an essential role in managing such medical conditions, thus improving the continuum of health care approach, physical and mental wellbeing of refugees and reducing the risk for severe COVID-19 disease among this group, taking us one step forward toward universal health access.Keywords: COVID-19, refugees, mobile clinics, primary health care
Procedia PDF Downloads 1423396 Incorporating Lexical-Semantic Knowledge into Convolutional Neural Network Framework for Pediatric Disease Diagnosis
Authors: Xiaocong Liu, Huazhen Wang, Ting He, Xiaozheng Li, Weihan Zhang, Jian Chen
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The utilization of electronic medical record (EMR) data to establish the disease diagnosis model has become an important research content of biomedical informatics. Deep learning can automatically extract features from the massive data, which brings about breakthroughs in the study of EMR data. The challenge is that deep learning lacks semantic knowledge, which leads to impracticability in medical science. This research proposes a method of incorporating lexical-semantic knowledge from abundant entities into a convolutional neural network (CNN) framework for pediatric disease diagnosis. Firstly, medical terms are vectorized into Lexical Semantic Vectors (LSV), which are concatenated with the embedded word vectors of word2vec to enrich the feature representation. Secondly, the semantic distribution of medical terms serves as Semantic Decision Guide (SDG) for the optimization of deep learning models. The study evaluate the performance of LSV-SDG-CNN model on four kinds of Chinese EMR datasets. Additionally, CNN, LSV-CNN, and SDG-CNN are designed as baseline models for comparison. The experimental results show that LSV-SDG-CNN model outperforms baseline models on four kinds of Chinese EMR datasets. The best configuration of the model yielded an F1 score of 86.20%. The results clearly demonstrate that CNN has been effectively guided and optimized by lexical-semantic knowledge, and LSV-SDG-CNN model improves the disease classification accuracy with a clear margin.Keywords: convolutional neural network, electronic medical record, feature representation, lexical semantics, semantic decision
Procedia PDF Downloads 1263395 The Occurrence of Clavibacter michiganensis subsp. sepedonicus on Potato in South Sulawesi, Indonesia
Authors: Baharuddin Patandjengi, A. Pabborong, T. Kuswinanti
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Bacterial ring rot caused by a gram-positive Coryneform bacterium Corynebacterium michiganensis subsp. sepedonicus is an important disease on potato crops in the world. The disease still belongs to an A1 quarantine pathogen in Indonesia, although it was found in West Java since 2013. The objective of this study was to know the presence of bacterial ring rot in four potato district areas in South Sulawesi. Infected samples were collected from potato fields and storage warehouses in Enrekang, Gowa, Jeneponto and Bantaeng districts. Potato tuber samples were cut and observed their vasiculer vessels and the bacterial ooze was used for isolation on Nutrient Agar and Nutrient Broth–Yeast extract medium. Bacterial isolates were then morphologically and physiologically characterized. A patogenicity test on eggplant and molecular characterization using PCR with specific primer for Cms (50F and Cms 50 R) was revealed for further identification. The results showed that Cms has become widespread in four districts of South Sulawesi. The bacterial ringrot disease incidence in these districts was reached above 30 %. All of 14 bacterial isolates that identified before using standard methods of EPPO, showed DNA band in size of 224 bp in PCR test, which indicated positively belong to C. michiganensis subsp. sepedonicus.Keywords: bacterial ring rot, clavibacter michiganensis pv. sepedonicus, PCR, potato
Procedia PDF Downloads 3353394 Prevalence of Life Style Diseases and Physical Activities among Older in India
Authors: Vaishali Chaurasia
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Ageing is the universal phenomenon that is associated with deteriorating health status. As the human becomes old, certain changes take place in an organism leading to morbidities, disabilities, and event death. Furthermore, older people are more vulnerable for the various kinds of diseases and health problem. Due to the some unhealthy conventions like smoking, drinking and unhealthy foods is the genesis of the lifestyle diseases. These diseases associated with the way a person or group of people lives. The main purpose of the study is to determine the prevalence of lifestyle diseases and its association with physical activity as well as the risk factors associated with it among the adult population in India. Longitudinal Aging Study in India and Study on Global Aging and Adult Health in India were used in the study. We will take population aged 50 and older, began in 1935, and regularly refreshed at younger ages with new birth cohorts. Life style diseases are more prominent in 65+ age group. The study finds an association between prevalence of life style diseases and life style risk factors. The lifestyle disease prevalence is more among higher age group people, female, richest quintile, and doing lesser physical activity. A higher prevalence of lifestyle diseases associated with the multiple risk factors. The occurrence of three and four risk factors was more prevalent in India. The frequency of different type of life style disease is higher among those who hardly or never do any physical activity as compare to those who do physical activity every day. The pattern remains the same in Moderate as well as vigorous physical activity. Those who are regularly doing physical activities have lesser percentage of having any disease and those who hardly ever or never do any physical activities and equally involve with some risk factors have higher percentage of having all type of diseases.Keywords: lifestyle disease, morbidity, disability, physical activity
Procedia PDF Downloads 3463393 Prediction of Covid-19 Cases and Current Situation of Italy and Its Different Regions Using Machine Learning Algorithm
Authors: Shafait Hussain Ali
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Since its outbreak in China, the Covid_19 19 disease has been caused by the corona virus SARS N coyote 2. Italy was the first Western country to be severely affected, and the first country to take drastic measures to control the disease. In start of December 2019, the sudden outbreaks of the Coronary Virus Disease was caused by a new Corona 2 virus (SARS-CO2) of acute respiratory syndrome in china city Wuhan. The World Health Organization declared the epidemic a public health emergency of international concern on January 30, 2020,. On February 14, 2020, 49,053 laboratory-confirmed deaths and 1481 deaths have been reported worldwide. The threat of the disease has forced most of the governments to implement various control measures. Therefore it becomes necessary to analyze the Italian data very carefully, in particular to investigates and to find out the present condition and the number of infected persons in the form of positive cases, death, hospitalized or some other features of infected persons will clear in simple form. So used such a model that will clearly shows the real facts and figures and also understandable to every readable person which can get some real benefit after reading it. The model used must includes(total positive cases, current positive cases, hospitalized patients, death, recovered peoples frequency rates ) all features that explains and clear the wide range facts in very simple form and helpful to administration of that country.Keywords: machine learning tools and techniques, rapid miner tool, Naive-Bayes algorithm, predictions
Procedia PDF Downloads 1083392 The Impact of Infectious Disease on Densely Populated Urban Area: In Terms of COVID-19
Authors: Samira Ghasempourkazemi
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In terms of the COVID-19 pandemic, lots of mutations in the urban system, which have systemic impacts, have clearly appeared. COVID-19 not only had a direct impact on health but also caused significant losses to other departments, including the economy, education, tourism, environment and the construction industry. Therefore, the pandemic caused a disruption in the whole urban system. Particularly, today’s large urban areas are not designed in order to be compatible during a pandemic. Hence, cities are more vulnerable to infectious disease threats according to the population density, built environment and socioeconomic aspects. Considering the direct relationship between population and rate of infection, higher rates are given to those individuals located in areas with high-density populations. Population density can be a factor that seems to have a strong impact on the spread of infectious diseases. Thus, the preliminary hypothesis can be related to a densely populated areas which become hotspots for the rapid spread of the pandemic due to high levels of interaction. In addition, some other indicators can be effective in this condition, such as age range, education and socio-economy. To figure out the measure of infectious disease risk in densely populated areas in Istanbul is an objective of this study. Besides, this study intends to figure out Vulnerability Index in the case of COVID-19. In order to achieve the proper result, the considered method can be Analytic Hierarchy Process (AHP) by involving the mentioned variables. In the end, the study represents the COVID Vulnerability of densely populated areas in a metro city and the gaps that need to be identified and plugged for the pandemic-resilience city of tomorrow.Keywords: infectious disease, COVID-19, urban system, densely populated area
Procedia PDF Downloads 833391 Diagnosis of Alzheimer Diseases in Early Step Using Support Vector Machine (SVM)
Authors: Amira Ben Rabeh, Faouzi Benzarti, Hamid Amiri, Mouna Bouaziz
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Alzheimer is a disease that affects the brain. It causes degeneration of nerve cells (neurons) and in particular cells involved in memory and intellectual functions. Early diagnosis of Alzheimer Diseases (AD) raises ethical questions, since there is, at present, no cure to offer to patients and medicines from therapeutic trials appear to slow the progression of the disease as moderate, accompanying side effects sometimes severe. In this context, analysis of medical images became, for clinical applications, an essential tool because it provides effective assistance both at diagnosis therapeutic follow-up. Computer Assisted Diagnostic systems (CAD) is one of the possible solutions to efficiently manage these images. In our work; we proposed an application to detect Alzheimer’s diseases. For detecting the disease in early stage we used the three sections: frontal to extract the Hippocampus (H), Sagittal to analysis the Corpus Callosum (CC) and axial to work with the variation features of the Cortex(C). Our method of classification is based on Support Vector Machine (SVM). The proposed system yields a 90.66% accuracy in the early diagnosis of the AD.Keywords: Alzheimer Diseases (AD), Computer Assisted Diagnostic(CAD), hippocampus, Corpus Callosum (CC), cortex, Support Vector Machine (SVM)
Procedia PDF Downloads 3853390 A Case Study of Deep Learning for Disease Detection in Crops
Authors: Felipe A. Guth, Shane Ward, Kevin McDonnell
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In the precision agriculture area, one of the main tasks is the automated detection of diseases in crops. Machine Learning algorithms have been studied in recent decades for such tasks in view of their potential for improving economic outcomes that automated disease detection may attain over crop fields. The latest generation of deep learning convolution neural networks has presented significant results in the area of image classification. In this way, this work has tested the implementation of an architecture of deep learning convolution neural network for the detection of diseases in different types of crops. A data augmentation strategy was used to meet the requirements of the algorithm implemented with a deep learning framework. Two test scenarios were deployed. The first scenario implemented a neural network under images extracted from a controlled environment while the second one took images both from the field and the controlled environment. The results evaluated the generalisation capacity of the neural networks in relation to the two types of images presented. Results yielded a general classification accuracy of 59% in scenario 1 and 96% in scenario 2.Keywords: convolutional neural networks, deep learning, disease detection, precision agriculture
Procedia PDF Downloads 2603389 Psychological Stress As A Catalyst For Multiple Sclerosis Progression: Clarifying Pathways From Neural Activation to Immune Dysregulation
Authors: Noah Emil Glisik
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Multiple sclerosis (MS) is a chronic, immune-mediated disorder characterized by neurodegenerative processes and a highly variable disease course. Recent research highlights a complex interplay between psychological stress and MS progression, with both acute and chronic stressors linked to heightened inflammatory activity, increased relapse risk, and accelerated disability. This review synthesizes findings from systematic analyses, cohort studies, and neuroimaging investigations to examine how stress contributes to disease dynamics in MS. Evidence suggests that psychological stress influences MS progression through neural and physiological pathways, including dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and heightened activity in specific brain regions, such as the insular cortex. Notably, functional MRI studies indicate that stress-induced neural activity may predict future atrophy in gray matter regions implicated in motor and cognitive function, thus supporting a neurobiological link between stress and neurodegeneration in MS. Longitudinal studies further associate chronic stress with reduced quality of life and higher relapse frequency, emphasizing the need for a multifaceted therapeutic approach that addresses both the physical and psychological dimensions of MS. Evidence from intervention studies suggests that stress management strategies, such as cognitive-behavioral therapy and mindfulness-based programs, may reduce relapse rates and mitigate lesion formation in MS patients. These findings underscore the importance of integrating stress-reducing interventions into standard MS care, with potential to improve disease outcomes and patient well-being. Further research is essential to clarify the causal pathways and develop targeted interventions that could modify the stress response in MS, offering an avenue to address disease progression and enhance quality of life.Keywords: multiple sclerosis, psychological stress, disease progression, neuroimaging, stress management
Procedia PDF Downloads 143388 Study on Health Status and Health Promotion Models for Prevention of Cardiovascular Disease in Asylum Seekers at Asylum Seekers Center, Kupang-Indonesia
Authors: Era Dorihi Kale, Sabina Gero, Uly Agustine
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Asylum seekers are people who come to other countries to get asylum. In line with that, they also carry the culture and health behavior of their country, which is very different from the new country they currently live in. This situation raises problems, also in the health sector. The approach taken must also be a culturally sensitive approach, where the culture and habits of the refugee's home area are also valued so that the health services provided can be right on target. Some risk factors that already exist in this group are lack of activity, consumption of fast food, smoking, and stress levels that are quite high. Overall this condition will increase the risk of an increased incidence of cardiovascular disease. This research is a descriptive and experimental study. The purpose of this study is to identify health status and develop a culturally sensitive health promotion model, especially related to the risk of cardiovascular disease for asylum seekers in detention homes in the city of Kupang. This research was carried out in 3 stages, stage 1 was conducting a survey of health problems and the risk of asylum seeker cardiovascular disease, Stage 2 developed a health promotion model, and stage 3 conducted a testing model of health promotion carried out. There were 81 respondents involved in this study. The variables measured were: health status, risk of cardiovascular disease and, health promotion models. Method of data collection: Instruments (questionnaires) were distributed to respondents answered for anamnese health status; then, cardiovascular risk measurements were taken. After that, the preparation of information needs and the compilation of booklets on the prevention of cardiovascular disease is carried out. The compiled booklet was then translated into Farsi. After that, the booklet was tested. Respondent characteristics: average lived in Indonesia for 4.38 years, the majority were male (90.1%), and most were aged 15-34 years (90.1%). There are several diseases that are often suffered by asylum seekers, namely: gastritis, headaches, diarrhea, acute respiratory infections, skin allergies, sore throat, cough, and depression. The level of risk for asylum seekers experiencing cardiovascular problems is 4 high risk people, 6 moderate risk people, and 71 low risk people. This condition needs special attention because the number of people at risk is quite high when compared to the age group of refugees. This is very related to the level of stress experienced by the refugees. The health promotion model that can be used is the transactional stress and coping model, using Persian (oral) and English for written information. It is recommended for health practitioners who care for refugees to always pay attention to aspects of culture (especially language) as well as the psychological condition of asylum seekers to make it easier to conduct health care and promotion. As well for further research, it is recommended to conduct research, especially relating to the effect of psychological stress on the risk of cardiovascular disease in asylum seekers.Keywords: asylum seekers, health status, cardiovascular disease, health promotion
Procedia PDF Downloads 1053387 A Different Approach to Smart Phone-Based Wheat Disease Detection System Using Deep Learning for Ethiopia
Authors: Nathenal Thomas Lambamo
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Based on the fact that more than 85% of the labor force and 90% of the export earnings are taken by agriculture in Ethiopia and it can be said that it is the backbone of the overall socio-economic activities in the country. Among the cereal crops that the agriculture sector provides for the country, wheat is the third-ranking one preceding teff and maize. In the present day, wheat is in higher demand related to the expansion of industries that use them as the main ingredient for their products. The local supply of wheat for these companies covers only 35 to 40% and the rest 60 to 65% percent is imported on behalf of potential customers that exhaust the country’s foreign currency reserves. The above facts show that the need for this crop in the country is too high and in reverse, the productivity of the crop is very less because of these reasons. Wheat disease is the most devastating disease that contributes a lot to this unbalance in the demand and supply status of the crop. It reduces both the yield and quality of the crop by 27% on average and up to 37% when it is severe. This study aims to detect the most frequent and degrading wheat diseases, Septoria and Leaf rust, using the most efficiently used subset of machine learning technology, deep learning. As a state of the art, a deep learning class classification technique called Convolutional Neural Network (CNN) has been used to detect diseases and has an accuracy of 99.01% is achieved.Keywords: septoria, leaf rust, deep learning, CNN
Procedia PDF Downloads 773386 Genome-Wide Association Study Identify COL2A1 as a Susceptibility Gene for the Hand Development Failure of Kashin-Beck Disease
Authors: Feng Zhang
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Kashin-Beck disease (KBD) is a chronic osteochondropathy. The mechanism of hand growth and development failure of KBD remains elusive now. In this study, we conducted a two-stage genome-wide association study (GWAS) of palmar length-width ratio (LWR) of KBD, totally involving 493 Chinese Han KBD patients. Affymetrix Genome Wide Human SNP Array 6.0 was applied for SNP genotyping. Association analysis was conducted by PLINK software. Imputation analysis was performed by IMPUTE against the reference panel of the 1000 genome project. In the GWAS, the most significant association was observed between palmar LWR and rs2071358 of COL2A1 gene (P value = 4.68×10-8). Imputation analysis identified 3 SNPs surrounding rs2071358 with significant or suggestive association signals. Replication study observed additional significant association signals at both rs2071358 (P value = 0.017) and rs4760608 (P value = 0.002) of COL2A1 gene after Bonferroni correction. Our results suggest that COL2A1 gene was a novel susceptibility gene involved in the growth and development failure of hand of KBD.Keywords: Kashin-Beck disease, genome-wide association study, COL2A1, hand
Procedia PDF Downloads 2213385 Factors Predicting Symptom Cluster Functional Status and Quality of Life of Chronic Obstructive Pulmonary Disease Patients
Authors: D. Supaporn, B. Julaluk
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The purposes of this study were to study symptom cluster, functional status and quality of life of patients with chronic obstructive pulmonary disease (COPD), and to examine factors related to and predicting symptom cluster, functional status and quality of life of COPD patients. The sample was 180 COPD patients multi-stage random sampling from 4 hospitals in the eastern region, Thailand. The research instruments were 8 questionnaires and recorded forms measuring personal and illness data, co-morbidity, physical and psychological symptom, health status perception, social support, and regimen adherence, functional status and quality of life. Spearman rank and Pearson correlation coefficient, exploratory factors analysis and standard multiple regression were used to analyzed data. The findings revealed that two symptom clusters were generated: physical symptom cluster including dyspnea, fatigue and insomnia; and, psychological symptom cluster including anxiety and depression. Scores of physical symptom cluster was at moderate level while that of psychological symptom cluster was at low level. Scores on functional status, social support and overall regimen adherence were at good level whereas scores on quality of life and health status perception were at moderate level. Disease severity was positively related to physical symptom cluster, psychological symptom cluster and quality of life, and was negatively related to functional status at a moderate level (rs = .512, .509, .588 and -.611, respectively). Co-morbidity was positively related to physical symptom cluster and psychological symptom cluster at a low level (r = .179 and .176, respectively). Regimen adherence was negatively related to quality of life and psychological symptom cluster at a low level (r=-.277 and -.309, respectively), and was positively related to functional status at a moderate level (r=.331). Health status perception was negatively related to physical symptom cluster, psychological symptom cluster and quality of life at a moderate to high level (r = -.567, -.640 and -.721, respectively) and was positively related to functional status at a high level (r = .732). Social support was positively related to functional status (r=.235) and was negatively related to quality of life at a low level (r=-.178). Physical symptom cluster was negatively related to functional status (r= -.490) and was positively related to quality of life at a moderate level (r=.566). Psychological symptom cluster was negatively related to functional status and was positively related to quality of life at a moderate level (r= -.566 and .559, respectively). Disease severity, co-morbidity and health status perception could predict 40.2% of the variance of physical symptom cluster. Disease severity, co-morbidity, regimen adherence and health status perception could predict 49.8% of the variance of psychological symptom cluster. Co-morbidity, regimen adherence and health status perception could predict 65.0% of the variance of functional status. Disease severity, health status perception and physical symptom cluster could predict 60.0% of the variance of quality of life in COPD patients. The results of this study can be used for enhancing quality of life of COPD patients.Keywords: chronic obstructive pulmonary disease, functional status, quality of life, symptom cluster
Procedia PDF Downloads 5593384 A Review of Type 2 Diabetes and Diabetes-Related Cardiovascular Disease in Zambia
Authors: Mwenya Mubanga, Sula Mazimba
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Background: In Zambia, much of the focus on nutrition and health has been on reducing micronutrient deficiencies, wasting and underweight malnutrition and not on the rising global projections of trends in obesity and type 2 diabetes. The aim of this review was to identify and collate studies on the prevalence of obesity, diabetes and diabetes-related cardiovascular disease conducted in Zambia, to summarize their findings and to identify areas that need further research. Methods: The Medical Literature Analysis and Retrieval System (MEDLINE) database was searched for peer-reviewed articles on the prevalence of, and factors associated with obesity, type 2 diabetes, and diabetes-related cardiovascular disease amongst Zambian residents using a combination of search terms. The period of search was from 1 January 2000 to 31 December 2016. We expanded the search terms to include all possible synonyms and spellings obtained in the search strategy. Additionally, we performed a manual search for other articles and references of peer-reviewed articles. Results: In Zambia, the current prevalence of Obesity and Type 2 diabetes is estimated at 13%-16% and 2.0 – 3.0% respectively. Risk factors such as the adoption of western dietary habits, the social stigmatization associated with rapid weight loss due to Tuberculosis and/ or the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and rapid urbanization have all been blamed for fueling the increased risk of obesity and type 2 diabetes. However, unlike traditional Western populations, those with no formal education were less likely to be obese than those who attained secondary or tertiary level education. Approximately 30% of those surveyed were unaware of their diabetes diagnosis and more than 60% were not on treatment despite a known diabetic status. Socio-demographic factors such as older age, female sex, urban dwelling, lack of tobacco use and marital status were associated with an increased risk of obesity, impaired glucose tolerance and type 2 diabetes. We were unable to identify studies that specifically looked at diabetes-related cardiovascular disease. Conclusion: Although the prevalence of Obesity and Type 2 diabetes in Zambia appears low, more representative studies focusing on parts of the country outside of the main industrial zone need to be conducted. There also needs to be research on diabetes-related cardiovascular disease. National surveillance, monitoring and evaluation on all non-communicable diseases need to be prioritized and policies that address underweight, obesity and type 2 diabetes developed.Keywords: type 2 diabetes, Zambia, obesity, cardiovascular disease
Procedia PDF Downloads 2543383 Study and Analysis of a Susceptible Infective Susceptible Mathematical Model with Density Dependent Migration
Authors: Jitendra Singh, Vivek Kumar
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In this paper, a susceptible infective susceptible mathematical model is proposed and analyzed where the migration of human population is given by migration function. It is assumed that the disease is transmitted by direct contact of susceptible and infective populations with constant contact rate. The equilibria and their stability are studied by using the stability theory of ordinary differential equations and computer simulation. The model analysis shows that the spread of infectious disease increases when human population immigration increases in the habitat but it decreases if emigration increases.Keywords: SIS (Susceptible Infective Susceptible) model, migration function, susceptible, stability
Procedia PDF Downloads 2643382 Telemedicine and Telemonitoring for Interstitial Lung Disease Patients with Nintedanib
Authors: M. Brockes, S. Beck, A. Sigaroudi, C. Brockes
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Over the last few years, telemedicine and telemonitoring have become popular ways of treatment, especially in other chronic diseases. Therefore, this type of treatment methodology was also implemented in patients with interstitial lung disease (ILD). In January 2024, a new service for patients with interstitial lung disease (ILD) treated with Nintedanib was established, which contains daily telemonitoring (home spirometry, pulse oximetry, and daily level of activity), daily evaluation of parameters as well as a telemedical availability answered by doctors and telemedical specialists throughout 365 days per year. The main motivational points of this service are the early detection of first signs of exacerbations and/or other symptoms/complications, as well as easier access to healthcare professionals. The evaluation of the patient’s quality of life and the subjective feeling of safetyness was measured through patient-reported experience measurements (PREMs) and patient-reported outcome measurements (PROMs). Patients were introduced to the telemedical and telemonitoring service six months ago. Within this period, every sixty days, the questionnaires were conducted by the scientific employees. Due to the unlimited time frame of the long-term service, the evaluation has not been completed. The first analysis of patient-reported experience measurements (PREMs) and patient reported outcome measurements (PROMs) had shown an increased positive effect on the patients' quality of life as well as an increased positive effect on the subjective feeling of safety at home, plus a reduction and avoidance of secondary damages (e.g., exacerbations, deterioration of typical interstitial lung disease ILD symptoms and pharmaceutical side effects). The first results have shown a tendency that the telemedical treatment combined with telemonitoring at home and the encouragement of patients to actively participate in their healthcare has a positive effect on the patient’s overall well-being and could be implemented as a complementation of the traditional standard of care.Keywords: avoidance of secondary damages, interstitial lung disease, telemedicine and telemonitoring, subjective feeling of safety
Procedia PDF Downloads 233381 Implementation of a Multidisciplinary Weekly Safety Briefing in a Tertiary Paediatric Cardiothoracic Transplant Unit
Authors: Lauren Dhugga, Meena Parameswaran, David Blundell, Abbas Khushnood
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Context: A multidisciplinary weekly safety briefing was implemented at the Paediatric Cardiothoracic Unit at the Freeman Hospital in Newcastle-upon-Tyne. It is a tertiary referral centre with a quarternary cardiac paediatric intensive care unit and provides complexed care including heart and lung transplants, mechanical support and advanced heart failure assessment. Aim: The aim of this briefing is to provide a structured platform of communication, in an effort to improve efficiency, safety, and patient care. Problem: The paediatric cardiothoracic unit is made up of a vast multidisciplinary team including doctors, intensivists, anaesthetists, surgeons, specialist nurses, echocardiogram technicians, physiotherapists, psychologists, dentists, and dietitians. It provides care for children with congenital and acquired cardiac disease and is one of only two units in the UK to offer paediatric heart transplant. The complexity of cases means that there can be many teams involved in providing care to each patient, and frequent movement of children between ward, high dependency, and intensive care areas. Currently, there is no structured forum for communicating important information across the department, for example, staffing shortages, prescribing errors and significant events. Strategy: An initial survey questioning the need for better communication found 90% of respondents agreed that they could think of an incident that had occurred due to ineffective communication, and 85% felt that incident could have been avoided had there been a better form of communication. Lastly, 80% of respondents felt that a weekly 60 second safety briefing would be beneficial to improve communication within our multidisciplinary team. Based on those promising results, a weekly 60 second safety briefing was implemented to be conducted on a Monday morning. The safety briefing covered four key areas (SAFE): staffing, awareness, fix and events. This was to highlight any staffing gaps, any incident reports to be learned from, any issues that required fixing and any events including teachings for the week ahead. The teams were encouraged to email suggestions or issues to be raised for the week or to approach in person with information to add. The safety briefing was implemented using change theory. Effect: The safety briefing has been trialled over 6 weeks and has received a good buy in from staff across specialties. The aim is to embed this safety briefing into a weekly meeting using the PDSA cycle. There will be a second survey in one month to assess the efficacy of the safety briefing and to continue to improve the delivery of information. The project will be presented at the next clinical governance briefing to attract wider feedback and input from across the trust. Lessons: The briefing displays promise as a tool to improve vigilance and communication in a busy multi-disciplinary unit. We have learned about how to implement quality improvement and about the culture of our hospital - how hierarchy influences change. We demonstrate how to implement change through a grassroots process, using a junior led briefing to improve the efficiency, safety, and communication in the workplace.Keywords: briefing, communication, safety, team
Procedia PDF Downloads 1453380 Prey-Predator Eco-Epidemiological Model with Nonlinear Transmission Disease
Authors: Qamar J. A. Khan, Fatma Ahmed Al Kharousi
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A prey-predator eco-epidemiological model is studied where transmission of the disease between infected and uninfected prey is nonlinear. The interaction of the predator with infected and uninfected prey species depend on their numerical superiority. Harvesting of both uninfected and infected prey is considered. Stability analysis is carried out for equilibrium values. Using the parameter µ, the death rate of infected prey as a bifurcation parameter it is shown that Hopf bifurcation could occur. The theoretical results are compared with numerical results for different set of parameters.Keywords: bifurcation, optimal harvesting, predator, prey, stability
Procedia PDF Downloads 3033379 Psychological Well-Being and Perception of Disease Severity in People with Multiple Sclerosis, Who Underwent a Program of Self-Regulation to Promote Physical Activity
Authors: Luísa Pedro, José Pais-Ribeiro, João Páscoa Pinheiro
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Multiple Sclerosis (MS) is a chronic disease of the central nervous system that affects more often young adults in the prime of his career and personal development, with no cure and unknown causes. The most common signs and symptoms are fatigue, muscle weakness, changes in sensation, ataxia, changes in balance, gait difficulties, memory difficulties, cognitive impairment and difficulties in problem solving. MS is a relatively common neurological disorder in which various impairments and disabilities impact strongly on function and daily life activities. The aim of this study is to examine the implications of the program of self-regulation in the perception of illness and mental health (psychological well-being domain) in MS patients. MS is a relatively common neurological disorder in which various impairments and disabilities impact strongly on function and daily life activities. The aim of this study is to examine the implications of the program of self-regulation in the perception of illness and mental health (psychological well-being domain) in MS patients. After this, a set of exercises was implemented to be used in daily life activities, according to studies developed with MS patients. We asked the subjects the question “Please classify the severity of your disease?” and used the domain of psychological well-being, the Mental Health Inventory (MHI-38) at the beginning (time A) and end (time B) of the program of self-regulation. We used the Statistical Package for the Social Sciences (SPSS) version 20. A non-parametric statistical hypothesis test (Wilcoxon test) was used for the variable analysis. The intervention followed the recommendations of the Helsinki Declaration. The age range of the subjects was between 20 and 58 years with a mean age of 44 years. 58.3 % were women, 37.5 % were currently married, 67% were retired and the mean level of education was 12.5 years. In the correlation between the severity of the disease perception and psychological well before the self-regulation program, an obtained result (r = 0.26, p <0.05), then the self-regulation program, was (r = 0.37, p <0.01), from a low to moderate correlation. We conclude that the program of self-regulation for physical activity in patients with MS can improve the relationship between the perception of disease severity and psychological well-being.Keywords: psychological well-being, multiple sclerosis, self-regulation, physical activity
Procedia PDF Downloads 4913378 A Review of Pharmacological Prevention of Peri-and Post-Procedural Myocardial Injury After Percutaneous Coronary Intervention
Authors: Syed Dawood Md. Taimur, Md. Hasanur Rahman, Syeda Fahmida Afrin, Farzana Islam
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The concept of myocardial injury, although first recognized from animal studies, is now recognized as a clinical phenomenon that may result in microvascular damage, no-reflow phenomenon, myocardial stunning, myocardial hibernation and ischemic preconditioning. The final consequence of this event is left ventricular (LV) systolic dysfunction leading to increased morbidity and mortality. The typical clinical case of reperfusion injury occurs in acute myocardial infarction (MI) with ST segment elevation in which an occlusion of a major epicardial coronary artery is followed by recanalization of the artery. This may occur either spontaneously or by means of thrombolysis and/or by primary percutaneous coronary intervention (PCI) with efficient platelet inhibition by aspirin (acetylsalicylic acid), clopidogrel and glycoprotein IIb/IIIa inhibitors. In recent years, percutaneous coronary intervention (PCI) has become a well-established technique for the treatment of coronary artery disease. PCI improves symptoms in patients with coronary artery disease and it has been increasing the safety of procedures. However, peri- and post-procedural myocardial injury, including angiographical slow coronary flow, microvascular embolization, and elevated levels of cardiac enzyme, such as creatine kinase and troponin-T and -I, has also been reported even in elective cases. Furthermore, myocardial reperfusion injury at the beginning of myocardial reperfusion, which causes tissue damage and cardiac dysfunction, may occur in cases of the acute coronary syndrome. Because patients with myocardial injury is related to larger myocardial infarction and have a worse long-term prognosis than those without myocardial injury, it is important to prevent myocardial injury during and/or after PCI in patients with coronary artery disease. To date, many studies have demonstrated that adjunctive pharmacological treatment suppresses myocardial injury and increases coronary blood flow during PCI procedures. In this review, we highlight the usefulness of pharmacological treatment in combination with PCI in attenuating myocardial injury in patients with coronary artery disease.Keywords: coronary artery disease, percutaneous coronary intervention, myocardial injury, pharmacology
Procedia PDF Downloads 4533377 Production of Gluten-Free Bread Using Emulsifying Salts and Rennet Casein
Authors: A. Morina, S. Ö. Muti, M. Öztürk
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Celiac disease is a chronic intestinal disease observed in individuals with gluten intolerance. In this study, our aim was to create a protein matrix to mimic the functional properties of gluten. For this purpose, rennet casein and four emulsifying salts (disodium phosphate (DSP), tetrasodium pyrophosphate (TSPP), sodium acid pyrophosphate (SAPP), and sodium hexametaphosphate (SHMP)) were investigated in gluten-free bread manufacture. Compositional, textural, and visual properties of the gluten-free bread dough and gluten-free breads were investigated by a two–level factorial experimental design with two-star points (α = 1.414) and two replicates of the center point. Manufacturing gluten-free bread with rennet casein and SHMP significantly increased the bread volume (P < 0.0001, R² = 97.8). In general, utilization of rennet casein with DSP and SAPP increased bread hardness while no difference was observed in samples manufactured with TSPP and SHMP. Except for TSPP, bread color was improved by the utilization of rennet casein and DSP, SAPP, and SHMP combinations. In conclusion, it is possible to manufacture gluten-free bread with acceptable texture and color by rennet casein and SHMP.Keywords: celiac disease, gluten-free bread, emulsified salts, rennet casein, rice flour
Procedia PDF Downloads 1713376 Oral Health Status in Sickle Cell Anemia Subjects
Authors: Surekha Rathod
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Sickle cell disease is a vascular disorder characterized by chronic, ongoing organ damage that is punctuated by episodes of acutely painful vascular complications.1 It is the most common genetic blood disorder in the United States, with about 2000 infants being identified through routine blood screenings annually, and an estimated 104,000-138,000 affected individuals living in the United States. Approximately 0.3%-1.3% of African American are affected by Sickle Cell Diseases (SCD).3 The aim of this paper is to present oral health status of patients with SCD. A total of 200 subjects of both sexes in the age group 18- 40 years were included in this study. The subjects were examined and the following indices were recorded • Oral hygiene index – Simplified (OHI-S). • Probing depths (PD). • Clinical Attachment Levels (CAL). • Gingival Index - Loe and Sillness. • Turesky Gillmore Glickman Modification of the Quigley Hein Plaque Index. (1970) • DMFT index. • Sickle Cell Disease Severity Index. A total of 1478 patients were screened of which 200 subjects were found to be diagnosed with SCD by electrophoresis. The study thus, included 200 subjects (111 females & 89 males) diagnosed with Sickle Cell Disease in the age group of 18-40 years. The probing pocket depths (PPD) were measured in millimeters. 36% had PPD in the range of 2-4mm, 48% had PPD in the range of 4-6mm while 16% had PPD of more than 6mm. Similar results were obtained for the Clinical Attachment Levels (CAL). 29.5 % subjects had CAL 2-4mm, 44.5% had 4-6mm & 26% had CAL 6mm & above. We can thus conclude that although oral health is not a priority for patients with SCD, it is supported by increased plaque accumulation. Because of the chronic anemic state of the patients with SCD, they should be encouraged to pay strict attention to oral hygiene instructions and practice.Keywords: chronic, genetic, oral, sickle cell disease, vascular
Procedia PDF Downloads 3993375 A Decrease in the Anxiety Levels of Participants with Autoimmune Disease: Efficacy of a Community-Based Educational Program
Authors: Jennifer Hunter, Francisco Ramirez, Neil A. Nedley, Thania Solorio, Christian Freed, Erica Kinjo
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People who have autoimmune disease are often at an increased risk for psychological disorders such as anxiety. Untreated psychological conditions can affect the development of disease and can affect one’s general quality of life. In this study, it was hypothesized that an educational community-based intervention would be useful in decreasing the anxiety levels of participants with autoimmune disease. Programs, 2-hours long each, were held weekly over a period of eight weeks. During every meeting, a 45-minute DVD presentation by a skilled physician was shown, a small group discussion was guided by trained facilitators, and weekly practical assignments were given to each participant. The focus of the program was to educate participants about healthy lifestyle behaviors such as exercise, nutrition, sleep hygiene, helpful thought patterns etc., and to provide a group environment in which each participant was supported. Participants were assessed pre-post program for anxiety using the Depression and Anxiety Assessment Test (registration TX 7-398-022), a validated mental health test based on DSM-5 criteria and demographics. Anxiety scores were classified according to the DSM-5 criteria into 4 categories: none (0-6), mild (7-10), moderate (11-19) or severe (20 or more). Out of the participants who participated in programs conducted in the manner explained above (n=431), the average age was 54.9 (SD 16.6) and 81.9% were female. At baseline, the mean group anxiety level was 9.4 (SD 5.4). Within the baseline group, anxiety levels were as follows: none (21.1%), mild (22.0%), moderate (27.1%) and severe (29.7%). After the program, mean group anxiety decreased to 4.7 (SD 4.0). Post-program anxiety levels were as follows: none (54.8%), mild (27.1%), moderate (12.5%), severe (5.6%). The decrease in overall anxiety levels was significant t(431)=19.3 p<.001, 95% CI [0.815, 1.041]. It was concluded that the eight-week intensive was beneficial in decreasing the anxiety levels of participants. A long-term follow-up study would be beneficial in determining how lasting such improvements are especially since autoimmune diseases are often chronic. Additionally, future studies that utilize a control group would aid in establishing whether the improvements seen are due to the use of this specific lifestyle-educational program.Keywords: anxiety, auto-immune disease, community-based educational program, lifestyle
Procedia PDF Downloads 1183374 Analysis of Efficacy and Safety of Abatacept for Rheumatoid Arthritis: A Systematic Review and Meta Analysis
Authors: Hamida Memon
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Rheumatoid arthritis (RA) is a persistent inflammation of the joints caused by an aggressive immune reaction leading to pain, stiffness, and limited function. Abatacept, a selective co-modulator, is a promising option for treatment and may have better safety profiles compared to other interventions. This meta-analysis aims at assessing the effectiveness and safety of abatacept in contrast to various RA treatments such as placebos, biological DMARDs and conventional DMARDs. The analysis assesses how abatacept influences disease activity, pain intensity and overall patient functionality. It weighs the risk factor of abatacept with other drugs such as tocilizumab, with the numbers being lower for abatacept. This meta-analysis aims at assessing the effectiveness and safety of abatacept in contrast to various RA treatments such as placebos, biological DMARDs and conventional DMARDs. The analysis assesses how abatacept influences disease activity, pain intensity and overall patient functionality. It weighs the risk factor of abatacept with other drugs such as tocilizumab, with the numbers being lower for abatacept.Keywords: Rheumatoid arthritis, abatacept, control group, bone disease
Procedia PDF Downloads 243373 A Computational Investigation of Potential Drugs for Cholesterol Regulation to Treat Alzheimer’s Disease
Authors: Marina Passero, Tianhua Zhai, Zuyi (Jacky) Huang
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Alzheimer’s disease has become a major public health issue, as indicated by the increasing populations of Americans living with Alzheimer’s disease. After decades of extensive research in Alzheimer’s disease, only seven drugs have been approved by Food and Drug Administration (FDA) to treat Alzheimer’s disease. Five of these drugs were designed to treat the dementia symptoms, and only two drugs (i.e., Aducanumab and Lecanemab) target the progression of Alzheimer’s disease, especially the accumulation of amyloid-b plaques. However, controversial comments were raised for the accelerated approvals of either Aducanumab or Lecanemab, especially with concerns on safety and side effects of these two drugs. There is still an urgent need for further drug discovery to target the biological processes involved in the progression of Alzheimer’s disease. Excessive cholesterol has been found to accumulate in the brain of those with Alzheimer’s disease. Cholesterol can be synthesized in both the blood and the brain, but the majority of biosynthesis in the adult brain takes place in astrocytes and is then transported to the neurons via ApoE. The blood brain barrier separates cholesterol metabolism in the brain from the rest of the body. Various proteins contribute to the metabolism of cholesterol in the brain, which offer potential targets for Alzheimer’s treatment. In the astrocytes, SREBP cleavage-activating protein (SCAP) binds to Sterol Regulatory Element-binding Protein 2 (SREBP2) in order to transport the complex from the endoplasmic reticulum to the Golgi apparatus. Cholesterol is secreted out of the astrocytes by ATP-Binding Cassette A1 (ABCA1) transporter. Lipoprotein receptors such as triggering receptor expressed on myeloid cells 2 (TREM2) internalize cholesterol into the microglia, while lipoprotein receptors such as Low-density lipoprotein receptor-related protein 1 (LRP1) internalize cholesterol into the neuron. Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1) converts excess cholesterol to 24S-hydroxycholesterol (24S-OHC). Cholesterol has been approved for its direct effect on the production of amyloid-beta and tau proteins. The addition of cholesterol to the brain promotes the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), secretase, and amyloid precursor protein (APP), which all aid in amyloid-beta production. The reduction of cholesterol esters in the brain have been found to reduce phosphorylated tau levels in mice. In this work, a computational pipeline was developed to identify the protein targets involved in cholesterol regulation in brain and further to identify chemical compounds as the inhibitors of a selected protein target. Since extensive evidence shows the strong correlation between brain cholesterol regulation and Alzheimer’s disease, a detailed literature review on genes or pathways related to the brain cholesterol synthesis and regulation was first conducted in this work. An interaction network was then built for those genes so that the top gene targets were identified. The involvement of these genes in Alzheimer’s disease progression was discussed, which was followed by the investigation of existing clinical trials for those targets. A ligand-protein docking program was finally developed to screen 1.5 million chemical compounds for the selected protein target. A machine learning program was developed to evaluate and predict the binding interaction between chemical compounds and the protein target. The results from this work pave the way for further drug discovery to regulate brain cholesterol to combat Alzheimer’s disease.Keywords: Alzheimer’s disease, drug discovery, ligand-protein docking, gene-network analysis, cholesterol regulation
Procedia PDF Downloads 763372 GABARAPL1 (GEC1) mRNA Expression Levels in Patients with Alzheimer's Disease
Authors: Ali Bayram, Burak Uz, Ilhan Dolasik, Remzi Yiğiter
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The GABARAP (GABAA-receptor-associated protein) family consists of GABARAP, GABARAPL1 (GABARAP-like 1) and GABARAPL2 (GABARAP-like 2). GABARAPL1, like GABARAP, was described to interact with both GABAA receptor and tubulin, and to be involved in intracellular GABAA receptor trafficking and promoting tubulin polymerization. In addition, GABARAPL1 is thought to be involved in various physiological (autophagosome closure, regulation of circadian rhythms) and/or pathological mechanisms (cancer, neurodegeneration). Alzheimer’s disease (AD) is a progressive neuro degenerative disorder characterized with impaired cognitive functions. Disruption of the GABAergic neuro transmission as well as cholinergic and glutamatergic interactions, may also be involved in the pathogenesis of AD. GABARAPL1 presents a regulated tissue expression and is the most expressed gene among the GABARAP family members in the central nervous system. We, herein, conducted a study to investigate the GABARAPL1 mRNA expression levels in patients with AD. 50 patients with AD and 49 control patients were enrolled to the present study. Messenger RNA expression levels of GABARAPL1 were detected by real-time polymerase chain reaction. GABARAPL1 mRNA expression in AD / control patients was 0,495 (95% confidence interval: 0,404-0,607), p= 0,00000002646. Reduced activity of GABARAPL1 gene might play a role, at least partly, in the pathophysiology of AD.Keywords: Alzheimer’s disease, GABARAPL1, mRNA expression, RT-PCR
Procedia PDF Downloads 4593371 In vitro Control of Mycosphaerella arachidis Deighton the Early Leaf Spot Disease Pathogen of Groundnut by the Extracts from Six Medicinal Plants
Authors: Matthew Omoniyi Adebola, Jude E Amadi
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Ground nut (Arachis hypogaea) is one of the most popular commercial crops in Nigeria. Its suc-cessful production has been drastically affected by early leaf spot disease caused by Mycosphae-rella arachidis Deighton. In vitro control of the pathogen by six medicinal plants (Entada afri-cana, Vitex doniana, Lawsonia inermis, Azadirachta indica, Acalypha hispida and Nuaclea lati-folia) was assessed in this study. The extracts of the plants were prepared using cold and hot wa-ter and alcohol. The pathogen was isolated from ground nut infected with early leaf spot disease. The results revealed a great significant difference (P<0.05) in yield of extracts between cold water, hot water, and alcohol extracts. A significant difference (P<0.05) was observed in percentage concentrations of the various phytochemical constituents present in the extracts. Flavonoids per-centage concentration was the highest (0.68 - 1.95%) followed by saponnin(0.09-1.53%) in N. latifolia extracts. Steroiods had the least percentage concentrations (0.00- 0.09%)followed by terpenoids(0.02–0.71%) and proanthocyannin (0.05 – 0.86%). N. latifolia extracts produced the highest percentage concentrations (0.07–1.95%) of all the phytochemicals followed by A. indi-ca(0.05–1.64%)and least concentrations were obtained in A. hispidia(0.09 – 0.87%)and V. do-niana (0.00–0.88%). The extracts inhibited spore germination and growth of M. arachidis. The inhibition by alcohol extracts was high and significantly different (P>0.05) from cold and hot water extracts. Alcohol extract of L. inermis gave 100% spore germination inhibition followed by N. latifolia and A.indica with 97.75% and 85.60% inhibition respectively. Therefore, field trials of these six medicinal plants on the control of early leaf spot disease of ground nut are rec-ommended.Keywords: groundnut, phytochemicals, medicinal plants, extracts, inhibition
Procedia PDF Downloads 2973370 Role of Pro-Inflammatory and Regulatory Cytokines in Pathogenesis of Graves’ Disease in Association with Autoantibody Thyroid and Regulatory FoxP3 T-Cells
Authors: Dwitya Elvira, Eryati Darwin
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Background: Graves’ disease (GD) is an autoimmune thyroid disease. Imbalance of Th1/Th2 cells and T-regulatory (Treg)/Th17 cells was thought to play pivotal role in the pathogenesis of GD. Treg FoxP3 produced TGF-β to maintain regulatory function, and Th17 cells produced IL-17 as cytokines that were thought in mediating several autoimmune diseases. The aim of this study is to assess the role of IL-17 and TGF-β in the pathogenesis of GD and to investigate its correlation with Thyroid Stimulating Hormone Receptor Antibody (TRAb) and Treg FoxP3 expression. Method: 30 GD patients and 27 age and sex-matched controls were enrolled in this study. Diagnosis of GD was based on clinical and biochemical of GD. Serum IL-17, TGF-β, TRAb, and FoxP3 were measured by enzyme-linked immunosorbent assay (ELISA). Data were analyzed by using SPSS 21.0 (SPSS Inc.). Spearman rank correlation test was used for assessment of correlation. The statistical significance was accepted as P<0.05. Result: There was no significant correlation between IL-17 and TGF-β serum with expression of FoxP3 level in GD, but there was significant correlation between TGF-β and TRAb serum level (P<0.05). Serum levels of IL-17 and TGF-β were found to be elevated in patient group compared to control, where mean values of IL-17 were 14.43±2.15 pg/mL and TGF-β were 10.44±3.19 pg/mL in patients group; and in control group, level of IL-17 were 7.1±1.45 pg/mL and TGF-β were 4.95±1.35 pg/mL. Conclusion: Serum Il-17 and TGF-β were elevated in GD patients that reflect the role of inflammatory and regulatory cytokines activation in pathogenesis of GD. There was significant correlation between TGF-β and TRAb, revealing that Treg cytokines may play a role in pathogenesis of GD.Keywords: IL-17, TGF-B, FoxP3, TRAb, Graves’ disease
Procedia PDF Downloads 2863369 Mutation Analysis of the ATP7B Gene in 43 Vietnamese Wilson’s Disease Patients
Authors: Huong M. T. Nguyen, Hoa A. P. Nguyen, Mai P. T. Nguyen, Ngoc D. Ngo, Van T. Ta, Hai T. Le, Chi V. Phan
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Wilson’s disease (WD) is an autosomal recessive disorder of the copper metabolism, which is caused by a mutation in the copper-transporting P-type ATPase (ATP7B). The mechanism of this disease is the failure of hepatic excretion of copper to bile, and leads to copper deposits in the liver and other organs. The ATP7B gene is located on the long arm of chromosome 13 (13q14.3). This study aimed to investigate the gene mutation in the Vietnamese patients with WD, and make a presymptomatic diagnosis for their familial members. Forty-three WD patients and their 65 siblings were identified as having ATP7B gene mutations. Genomic DNA was extracted from peripheral blood samples; 21 exons and exon-intron boundaries of the ATP7B gene were analyzed by direct sequencing. We recognized four mutations ([R723=; H724Tfs*34], V1042Cfs*79, D1027H, and IVS6+3A>G) in the sum of 20 detectable mutations, accounting for 87.2% of the total. Mutation S105* was determined to have a high rate (32.6%) in this study. The hotspot regions of ATP7B were found at exons 2, 16, and 8, and intron 14, in 39.6 %, 11.6 %, 9.3%, and 7 % of patients, respectively. Among nine homozygote/compound heterozygote siblings of the patients with WD, three individuals were determined as asymptomatic by screening mutations of the probands. They would begin treatment after diagnosis. In conclusion, 20 different mutations were detected in 43 WD patients. Of this number, four novel mutations were explored, including [R723=; H724Tfs*34], V1042Cfs*79, D1027H, and IVS6+3A>G. The mutation S105* is the most prevalent and has been considered as a biomarker that can be used in a rapid detection assay for diagnosis of WD patients. Exons 2, 8, and 16, and intron 14 should be screened initially for WD patients in Vietnam. Based on risk profile for WD, genetic testing for presymptomatic patients is also useful in diagnosis and treatment.Keywords: ATP7B gene, mutation detection, presymptomatic diagnosis, Vietnamese Wilson’s disease
Procedia PDF Downloads 3803368 Defective Autophagy Disturbs Neural Migration and Network Activity in hiPSC-Derived Cockayne Syndrome B Disease Models
Authors: Julia Kapr, Andrea Rossi, Haribaskar Ramachandran, Marius Pollet, Ilka Egger, Selina Dangeleit, Katharina Koch, Jean Krutmann, Ellen Fritsche
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It is widely acknowledged that animal models do not always represent human disease. Especially human brain development is difficult to model in animals due to a variety of structural and functional species-specificities. This causes significant discrepancies between predicted and apparent drug efficacies in clinical trials and their subsequent failure. Emerging alternatives based on 3D in vitro approaches, such as human brain spheres or organoids, may in the future reduce and ultimately replace animal models. Here, we present a human induced pluripotent stem cell (hiPSC)-based 3D neural in a vitro disease model for the Cockayne Syndrome B (CSB). CSB is a rare hereditary disease and is accompanied by severe neurologic defects, such as microcephaly, ataxia and intellectual disability, with currently no treatment options. Therefore, the aim of this study is to investigate the molecular and cellular defects found in neural hiPSC-derived CSB models. Understanding the underlying pathology of CSB enables the development of treatment options. The two CSB models used in this study comprise a patient-derived hiPSC line and its isogenic control as well as a CSB-deficient cell line based on a healthy hiPSC line (IMR90-4) background thereby excluding genetic background-related effects. Neurally induced and differentiated brain sphere cultures were characterized via RNA Sequencing, western blot (WB), immunocytochemistry (ICC) and multielectrode arrays (MEAs). CSB-deficiency leads to an altered gene expression of markers for autophagy, focal adhesion and neural network formation. Cell migration was significantly reduced and electrical activity was significantly increased in the disease cell lines. These data hint that the cellular pathologies is possibly underlying CSB. By induction of autophagy, the migration phenotype could be partially rescued, suggesting a crucial role of disturbed autophagy in defective neural migration of the disease lines. Altered autophagy may also lead to inefficient mitophagy. Accordingly, disease cell lines were shown to have a lower mitochondrial base activity and a higher susceptibility to mitochondrial stress induced by rotenone. Since mitochondria play an important role in neurotransmitter cycling, we suggest that defective mitochondria may lead to altered electrical activity in the disease cell lines. Failure to clear the defective mitochondria by mitophagy and thus missing initiation cues for new mitochondrial production could potentiate this problem. With our data, we aim at establishing a disease adverse outcome pathway (AOP), thereby adding to the in-depth understanding of this multi-faced disorder and subsequently contributing to alternative drug development.Keywords: autophagy, disease modeling, in vitro, pluripotent stem cells
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