Search results for: swine respiratory disease
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4230

Search results for: swine respiratory disease

3690 Vitamin D Levels of Patients with Rheumatoid Arthritis in Kosova

Authors: Mjellma Rexhepi, Blerta Rexhepi Kelmendi, Blana Krasniqi, Shaip Krasniqi

Abstract:

Rheumatoid arthritis is a chronic disease that causes inflammation of the joints which can be so severe that can cause not only deformities but also impairment of function that limits movement. This also contributes to the pain that accompanies this disease. This remains a problematic and challenging disease of modern medicine because treatment is still symptomatic. The main purpose of drug treatment is to reduce the activity of the disease, achieve remission, avoid disability and death. The etiology of the disease is idiopathic, but can also be linked to genetic, nongenetic factors such as hormonal, environmental or infectious. Current scientific evidence shows that vitamin D plays an important role in immune regulation mechanisms. Lack of this vitamin has been linked to loss of immune tolerance and the appearance of autoimmune processes, including rheumatoid arthritis. The purpose of the work was to define Vitamin D in patients hospitalized with rheumatoid arthritis in University Clinical Center of Kosova, as a basis of their connection with lifestyle and physical inactivity. The sample for the work was selected from patients with criteria met for rheumatoid arthritis who were hospitalized at the tertiary level of health care in Kosova. During the work have been investigated 100 consecutive patients fulfilling diagnostic criteria for rheumatoid arthritis, whereas in addition to the general characteristics are also determined the values of vitamin D at the beginning of hospitalization. The average age of the sample analyzed was 50.9±5.7 years old, with an average duration of rheumatoid arthritis disease 7.8±3.4 years. At the beginning of hospitalization, before treatment was initiated, the average value of vitamin D was 15.86±3.43, which according to current reference values is classified into the category of insufficient values. Correlating the duration of the disease, from the time of diagnosis to the day of hospitalization, on one side and the level of vitamin D on the other side, the negative correlation of a lower degree derived (r =-0.1). Physical activity affects the concentration of vitamin D in the blood through increased metabolism of fat and the release of vitamin D and its metabolites from adipose tissue. To now it is evident that physical activity is also accompanied by higher levels of vitamin D. In patients with rheumatoid arthritis, vitamin D levels were low compared to normal. Future works should be oriented toward investigating in detail the bone structure, quality of life and pain in patients with rheumatoid arthritis. More detailed scientific projects, with larger numbers of participants, should be designed for the future to clarify more possible mechanisms as factors related to this phenomenon such as inactivity, lifestyle and the duration of the disease, as well as the importance of keeping vitamin D values at normal limits.

Keywords: hospitalization, lifestyle, rheumatoid arthritis, vitamin D

Procedia PDF Downloads 15
3689 Investigation of the Excitotoxicity Pathways in Neuroblastoma Cells

Authors: Merve Colak, Gizem Donmez Yalcin

Abstract:

Glutamate has many neurological functions in the central nervous system and is found at high concentrations in the brain. Increased levels of glutamate in the neuronal space are toxic, causing neuron damage and death. This is called glutamate-induced excitotoxicity. Excitotoxicity is among the causes of many neurological diseases such as trauma, cerebral ischemia, epilepsy, Parkinson's Disease, Alzheimer's Disease. Since neuroblastoma cells are known to be excitotoxic, we propose that excitotoxicity can be studied in neuroblastoma cells. Excitotoxicity can be induced using kainic acid in neuroblastoma cells. Measuring the secretion of glutamate, excitotoxicity can be analyzed in neuroblastoma cells.

Keywords: glutamate, excitotoxicity, kainic acid, Sirt4

Procedia PDF Downloads 158
3688 Optimization of Ultrasound-Assisted Extraction and Microwave-Assisted Acid Digestion for the Determination of Heavy Metals in Tea Samples

Authors: Abu Harera Nadeem, Kingsley Donkor

Abstract:

Tea is a popular beverage due to its flavour, aroma and antioxidant properties—with the most consumed varieties being green and black tea. Antioxidants in tea can lower the risk of Alzheimer’s and heart disease and obesity. However, these teas contain heavy metals such as Hg, Cd, or Pb, which can cause autoimmune diseases like Graves disease. In this study, 11 heavy metals in various commercial green, black, and oolong tea samples were determined using inductively coupled plasma-mass spectrometry (ICP-MS). Two methods of sample preparation were compared for accuracy and precision, which were microwave-assisted digestion and ultrasonic-assisted extraction. The developed method was further validated by detection limit, precision, and accuracy. Results showed that the proposed method was highly sensitive with detection limits within parts-per-billion levels. Reasonable method accuracy was obtained by spiked experiments. The findings of this study can be used to delve into the link between tea consumption and disease and to provide information for future studies on metal determination in tea.

Keywords: ICP-MS, green tea, black tea, microwave-assisted acid digestion, ultrasound-assisted extraction

Procedia PDF Downloads 123
3687 Autoimmune Diseases Associated to Autoimmune Hepatitis: A Retrospective Study of 24 Tunisian Patients

Authors: Soumaya Mrabet, Imen Akkari, Amira Atig, Elhem Ben Jazia

Abstract:

Introduction: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease of unknown cause. Concomitant autoimmune disorders have been described in 30–50% of patients with AIH. The aim of our study is to determine the prevalence and the type of autoimmune disorders associated with AIH. Material and Methods: It is a retrospective study over a period of 16 years (2000-2015) including all patients followed for AIH. The diagnosis of AHI was based on the criteria of the revised International AIH group scoring system (IAIHG). Results: Twenty-for patients (21 women and 3 men) followed for AIH were collected. The mean age was 39 years (17-65 years). Among these patients, 11 patients(45.8%) had at least one autoimmune disease associated to AIH. These diseases were Hashimoto's thyroiditis (n = 5), Gougerot Sjogren syndrome (n=5), Primary biliary cirrhosis (n=2), Primitive sclerosant Cholangitis (n=1), Addison disease (n = 1) and systemic sclerosis (n=1). Patients were treated with corticosteroids alone or with azathioprine associated to the specific treatment of associated diseases with complete remission of AIH in 90% of cases and clinical improvement of other diseases. Conclusion: In our study, the prevalence of autoimmune diseases in AIH patients was 45.8%. These diseases were dominated by autoimmune thyroiditis and Gougerot Sjogren syndrome. The investigation of autoimmune diseases in autoimmune hepatitis must be systematic because of their frequency and the importance of adequate management.

Keywords: autoimmune diseases, autoimmune hepatitis, autoimmune thyroiditis, gougerot sjogren syndrome

Procedia PDF Downloads 263
3686 The Association between Prior Antibiotic Use and Subsequent Risk of Infectious Disease: A Systematic Review

Authors: Umer Malik, David Armstrong, Mark Ashworth, Alex Dregan, Veline L'Esperance, Lucy McDonnell, Mariam Molokhia, Patrick White

Abstract:

Introduction: The microbiota lining epithelial surfaces is thought to play an important role in many human physiological functions including defense against pathogens and modulation of immune response. The microbiota is susceptible to disruption from external influences such as exposure to antibiotic medication. It is thought that antibiotic-induced disruption of the microbiota could predispose to pathogen overgrowth and invasion. We hypothesized that antibiotic use would be associated with increased risk of future infections. We carried out a systematic review of evidence of associations between antibiotic use and subsequent risk of community-acquired infections. Methods: We conducted a review of the literature for observational studies assessing the association between antibiotic use and subsequent community-acquired infection. Eligible studies were published before April 29th, 2016. We searched MEDLINE, EMBASE, and Web of Science and screened titles and abstracts using a predefined search strategy. Infections caused by Clostridium difficile, drug-resistant organisms and fungal organisms were excluded as their association with prior antibiotic use has been examined in previous systematic reviews. Results: Eighteen out of 21,518 retrieved studies met the inclusion criteria. The association between past antibiotic exposure and subsequent increased risk of infection was reported in 16 studies, including one study on Campylobacter jejuni infection (Odds Ratio [OR] 3.3), two on typhoid fever (ORs 5.7 and 12.2), one on Staphylococcus aureus skin infection (OR 2.9), one on invasive pneumococcal disease (OR 1.57), one on recurrent furunculosis (OR 16.6), one on recurrent boils and abscesses (Risk ratio 1.4), one on upper respiratory tract infection (OR 2.3) and urinary tract infection (OR 1.1), one on invasive Haemophilus influenzae type b (Hib) infection (OR 1.51), one on infectious mastitis (OR 5.38), one on meningitis (OR 2.04) and five on Salmonella enteric infection (ORs 1.4, 1.59, 1.9, 2.3 and 3.8). The effect size in three studies on Salmonella enteric infection was of marginal statistical significance. A further two studies on Salmonella infection did not demonstrate a statistically significant association between prior antibiotic exposure and subsequent infection. Conclusion: We have found an association between past antibiotic exposure and subsequent risk of a diverse range of infections in the community setting. Our findings provide evidence to support the hypothesis that prior antibiotic usage may predispose to future infection risk, possibly through antibiotic-induced alteration of the microbiota. The findings add further weight to calls to minimize inappropriate antibiotic prescriptions.

Keywords: antibiotic, infection, risk factor, side effect

Procedia PDF Downloads 224
3685 Changes in Serum Hepcidin Levels in Children with Inflammatory Bowel Disease during Anti-Inflammatory Treatment

Authors: Eva Karaskova, Jana Volejnikova, Dusan Holub, Maria Velganova-Veghova, Michaela Spenerova, Dagmar Pospisilova

Abstract:

Background: Hepcidin is the central regulator of iron metabolism. Its production is mainly affected by an iron deficiency and the presence of inflammatory activity in the body. The aim of this study was to compare serum hepcidin levels in paediatric patients with newly diagnosed inflammatory bowel disease and hepcidin levels during maintenance therapy, correlate changes of serum hepcidin levels with selected markers of iron metabolism and inflammation and type of provided treatment. Methods: Children with newly diagnosed Crohn's disease (CD) and ulcerative colitis (UC) were included in this prospective study. Blood and stool samples were collected before treatment (baseline). Serum hepcidin, hemoglobin levels, platelet counts, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-6 (IL 6), ferritin, iron, soluble transferrin receptors, and fecal calprotectin were assessed. The same parameters were measured and compared with the baseline levels in the follow-up period, during maintenance therapy (average of 39 months after diagnosis). Results: Patients with CD (n=30) had higher serum hepcidin levels (expressed as a median and interquartile range) at diagnosis than subjects with UC (n=13). These levels significantly decreased during the follow-up (from 36.5 (11.5-79.6) ng/ml to 2.1 (0.9-6.7) ng/ml). Contrarily, no significant serum hepcidin level changes were observed in UC (from 5.4 (3.4-16.6) ng/ml to 4.8 (0.9-8.1) ng/ml). While in children with CD hepcidin level dynamics correlated with disease activity and inflammatory markers (ESR, CRP), an only correlation with serum iron levels was observed in patients with UC. Conclusion: Children with CD had higher serum hepcidin levels at diagnosis compared to subjects with UC. Decrease of serum hepcidin in the CD group during anti-inflammatory therapy has been observed, whereas low hepcidin levels in children with UC have remained unchanged. Acknowledgment: This study was supported by grant MH CZ–DRO (FNOl, 00098892).

Keywords: children, Crohn's disease, ulcerative colitis, anaemia, hepcidin

Procedia PDF Downloads 123
3684 Parameter Estimation of Additive Genetic and Unique Environment (AE) Model on Diabetes Mellitus Type 2 Using Bayesian Method

Authors: Andi Darmawan, Dewi Retno Sari Saputro, Purnami Widyaningsih

Abstract:

Diabetes mellitus (DM) is a chronic disease in human that occurred if pancreas cannot produce enough of insulin hormone or the body uses ineffectively insulin hormone which causes increasing level of glucose in the blood, or it was called hyperglycemia. In Indonesia, DM is a serious disease on health because it can cause blindness, kidney disease, diabetic feet (gangrene), and stroke. The type of DM criteria can also be divided based on the main causes; they are DM type 1, type 2, and gestational. Diabetes type 1 or previously known as insulin-independent diabetes is due to a lack of production of insulin hormone. Diabetes type 2 or previously known as non-insulin dependent diabetes is due to ineffective use of insulin while gestational diabetes is a hyperglycemia that found during pregnancy. The most one type commonly found in patient is DM type 2. The main factors of this disease are genetic (A) and life style (E). Those disease with 2 factors can be constructed with additive genetic and unique environment (AE) model. In this article was discussed parameter estimation of AE model using Bayesian method and the inheritance character simulation on parent-offspring. On the AE model, there are response variable, predictor variables, and parameters were capable of representing the number of population on research. The population can be measured through a taken random sample. The response and predictor variables can be determined by sample while the parameters are unknown, so it was required to estimate the parameters based on the sample. Estimation of AE model parameters was obtained based on a joint posterior distribution. The simulation was conducted to get the value of genetic variance and life style variance. The results of simulation are 0.3600 for genetic variance and 0.0899 for life style variance. Therefore, the variance of genetic factor in DM type 2 is greater than life style.

Keywords: AE model, Bayesian method, diabetes mellitus type 2, genetic, life style

Procedia PDF Downloads 284
3683 Knowledge about Dementia: Why Should Family Caregivers Know that Dementia is a Terminal Disease?

Authors: Elzbieta Sikorska-Simmons

Abstract:

Dementia is a progressive terminal disease. Despite this recognition, research shows that most family caregivers do not know it, and it is unclear how this knowledge affects the quality of patient care. The aim of this qualitative study of 20 family caregivers for patients with advanced dementia is to examine how the caregiver's knowledge about dementia affects the quality of patient care in the context of healthcare decision-making, advanced care planning, and access to adequate support systems. Knowledge about dementia implies family caregivers' understanding of dementia trajectories, common symptoms/complications, and alternative treatment options (e.g., comfort feeding versus tube feeding). Data were collected in semi-structured interviews with 20 family caregivers. The interviews were conducted in person by the author and designed to elicit rich descriptions of family caregivers' experiences with healthcare decision-making and the management of common symptoms/complications of end-stage dementia as patient healthcare proxies. The study findings suggest that caregivers who recognize that dementia is a terminal disease are less likely to opt for life-extending treatments during the advanced stages. They are also more likely to seek palliative/hospice care, and consequently, they are better able to avoid unnecessary hospitalizations or medical procedures. For example, those who know that dementia is a terminal disease tend to opt for "comfort feeding" rather than "tube feeding" in managing the swallowing difficulties that accompany advanced dementia. In the context of advance care planning, family caregivers who know that dementia is a terminal disease tend to have more meaningful advance directives (e.g., Power of Attorney and Do Not Resuscitate orders). They are better prepared to anticipate common problems and pursue treatments that foster the best quality of patient life and care. Greater knowledge about advanced dementia helps them make more informed decisions that focus on enhancing the quality of patient life rather than just survival. In addition, those who know that dementia is a terminal disease are more likely to establish adequate support systems to help them cope with the complex demands of caregiving. For example, they are more likely to seek dementia-oriented primary care programs that offer house visits or respite services. Based on the study findings, knowledge about dementia as a terminal disease is critical in the optimal management of patient care needs and the establishment of adequate support systems. More research is needed to better understand what caregivers need to know to better prepare them for the complex demands of dementia caregiving.

Keywords: dementia education, family caregiver, management of dementia, quality of care

Procedia PDF Downloads 100
3682 Study on the Knowledge, Attitude and Practice (KAP) of Patients with Hypertension in Aseer Hospital, Asir Region, Saudi Arabia

Authors: Ayesha Siddiqua

Abstract:

Background: Hypertension is a silent killer disease and a common risk factor for considerable morbidity and mortality. Its effects can be seen on the organs like Heart; Brain; Kidneys. In Saudi Arabia, hypertension affects a sizeable enough proportion of the population, with a prevalence of 27.9% in urban and 22.4 in rural population. Despite these features, the magnitude and epidemiological characteristics of this disease have been rarely studied in Saudi Arabia. To fill this gap, we conducted a survey in Abha to study the KAP of hypertension. KAP study shows what people know about certain things, their feelings and behavior towards the disease management. An improvement in the Knowledge and Attitudes towards disease management can reform the kinds of practices which are followed. Objectives: To assess the level of Knowledge, Attitude and Practice of patients who suffer from Hypertension. To improve the Quality of life of patients. Methods: A prospective cross-sectional survey was conducted on a sample size of 130 Hypertensive patients of both the genders enrolled by simple random sampling technique admitted in the Aseer Central Hospital of Abha during the period from October 2016 to December 2016. Results: Altogether 130 hypertensive patients were enrolled in this study with equal no. of Males and Females. Most of the respondents were aged between 18-40 years (45%). On assessing the KAP of the patients, we found that the Knowledge and Attitude score was good but the Practice scores were moderate in both the genders. Conclusion: Our study concludes that a significant proportion of hypertensive patients show less Practice towards the disease management which can lead to severe complications in time being and also result in damage of other vital organs. So there is a need of intense educational intervention for the patients which can be done by Patient counselling by the clinical pharmacist. Strategies to modify lifestyle which help in control of hypertension can include providing leaflets as well as direct educational programs.

Keywords: Attitude, hypertension, Knowledge, practices

Procedia PDF Downloads 350
3681 Reduction in Hospital Acquire Infections after Intervention of Hand Hygiene and Personal Protective Equipment at COVID Unit Indus Hospital Karachi

Authors: Aisha Maroof

Abstract:

Introduction: Coronavirus Disease 2019 (COVID-19) is spreading rapidly around the world with devastating consequences on patients, health care workers and health systems. Severe 2019 novel coronavirus infectious disease (COVID-19) with pneumonia is associated with high rates of admission to the intensive care unit (ICU) and they are at high risk to obtain the hospital acquire bloodstream infection (HAIs) such as central line associated bloodstream infection (CLABSI), catheter associated urinary tract infections (CAUTI) and laboratory confirm bloodstream infection (LCBSI). The chances of infection transmission increase when healthcare worker’s (HCWs) practice is inappropriate. Risk related to hand hygiene (HH) and personal protective equipment (PPE) as regards multidrug-resistant organism transmission: use of multiple gloving instead of HH and incorrect use of PPE can lead to a significant increase of device-related infections. As it reaches low- and middle-income countries, its effects could be even more, because it will be difficult for them to react aggressively to the pandemic. HAIs are one of the biggest medical concerns, resulting in increased mortality rates. Objective: To assess the effect of intervention on compliance of hand hygiene and PPE among HCWs reduce the rate of HAI in COVID-19 patients. Method: An interventional study was done between July to December, 2020. CLABSI, CAUTI and LCBSI data were collected from the medical record and direct observation. There were total of 50 Nurses, 18 doctors and all patients with laboratory-confirmed severe COVID-19 admitted to the hospital were included in this research study. Respiratory tract specimens were obtained after the first 48 h of ICU admission. Practices were observed after and before intervention. Education was provided based on WHO guidelines. Results: During the six months of study July to December, the rate of CLABSI, CAUTI and LCBSI pre and post intervention was reported. CLABSI rate decreasedd from 22.7 to 0, CAUTI rate was decreased from 1.6 to 0, LCBSI declined from 3.3 to 0 after implementation of intervention. Conclusion: HAIs are an important cause of morbidity and mortality. Most of the device related infections occurs due to lack of correct use of PPE and hand hygiene compliance. Hand hygiene and PPE is the most important measure to protect patients, through education it can be improved the correct use of PPE and hand hygiene compliance and can reduce the bacterial infection in COVID-19 patients.

Keywords: hospital acquire infection, healthcare workers, hand hygiene, personal protective equipment

Procedia PDF Downloads 129
3680 Analysis of NMDA Receptor 2B Subunit Gene (GRIN2B) mRNA Expression in the Peripheral Blood Mononuclear Cells of Alzheimer's Disease Patients

Authors: Ali̇ Bayram, Semih Dalkilic, Remzi Yigiter

Abstract:

N-methyl-D-aspartate (NMDA) receptor is a subtype of glutamate receptor and plays a pivotal role in learning, memory, neuronal plasticity, neurotoxicity and synaptic mechanisms. Animal experiments were suggested that glutamate-induced excitotoxic injuriy and NMDA receptor blockage lead to amnesia and other neurodegenerative diseases including Alzheimer’s disease (AD), Huntington’s disease, amyotrophic lateral sclerosis. Aim of this study is to investigate association between NMDA receptor coding gene GRIN2B expression level and Alzheimer disease. The study was approved by the local ethics committees, and it was conducted according to the principles of the Declaration of Helsinki and guidelines for the Good Clinical Practice. Peripheral blood was collected 50 patients who diagnosed AD and 49 healthy control individuals. Total RNA was isolated with RNeasy midi kit (Qiagen) according to manufacturer’s instructions. After checked RNA quality and quantity with spectrophotometer, GRIN2B expression levels were detected by quantitative real time PCR (QRT-PCR). Statistical analyses were performed, variance between two groups were compared with Mann Whitney U test in GraphpadInstat algorithm with 95 % confidence interval and p < 0.05. After statistical analyses, we have determined that GRIN2B expression levels were down regulated in AD patients group with respect to control group. But expression level of this gene in each group was showed high variability. İn this study, we have determined that NMDA receptor coding gene GRIN2B expression level was down regulated in AD patients when compared with healthy control individuals. According to our results, we have speculated that GRIN2B expression level was associated with AD. But it is necessary to validate these results with bigger sample size.

Keywords: Alzheimer’s disease, N-methyl-d-aspartate receptor, NR2B, GRIN2B, mRNA expression, RT-PCR

Procedia PDF Downloads 394
3679 The Best Prediction Data Mining Model for Breast Cancer Probability in Women Residents in Kabul

Authors: Mina Jafari, Kobra Hamraee, Saied Hossein Hosseini

Abstract:

The prediction of breast cancer disease is one of the challenges in medicine. In this paper we collected 528 records of women’s information who live in Kabul including demographic, life style, diet and pregnancy data. There are many classification algorithm in breast cancer prediction and tried to find the best model with most accurate result and lowest error rate. We evaluated some other common supervised algorithms in data mining to find the best model in prediction of breast cancer disease among afghan women living in Kabul regarding to momography result as target variable. For evaluating these algorithms we used Cross Validation which is an assured method for measuring the performance of models. After comparing error rate and accuracy of three models: Decision Tree, Naive Bays and Rule Induction, Decision Tree with accuracy of 94.06% and error rate of %15 is found the best model to predicting breast cancer disease based on the health care records.

Keywords: decision tree, breast cancer, probability, data mining

Procedia PDF Downloads 138
3678 Skin Diseases in the Rural Areas in Nepal; Impact on Quality of Life

Authors: Dwarika P. Shrestha, Dipendra Gurung, Rushma Shrestha, Inger Rosdahl

Abstract:

Introduction: Skin diseases are one of the most common health problems in Nepal. The objectives of this study are to determine the prevalence of skin diseases and impact on quality of life in rural areas in Nepal. Materials and methods: A house-to-house survey was conducted, to obtain socio-demographic data and identify individuals with skin diseases, followed by health camps, where the villagers were examined. A pilot study was conducted in one village, which was then extended to 10 villages in 4 districts. To assess the impact on quality of life, the villagers were interviewed with Skin Disease Disability Index. This is a questionnaire developed and validated by the authors for use in Nepal. Results: In the pilot study, the overall prevalence of skin diseases was 20.1% (645/3207). In the additional 10 villages with 7348 (3651/3787 m/f) inhabitants, 1862 (721/1141 m/f, mean age 31.4 years) had one or more skin diseases. The overall prevalence of skin diseases was 25%. The most common skin disease categories were eczemas (13.7%, percentage among all inhabitants) pigment disorders (6.8%), fungal infections (4.9%), nevi (3.7%) and urticaria (2.9%). These five most common skin disease categories comprise 71% of all skin diseases seen in the study. The mean skin disease disability index score was 13.7, indicating very large impact on the quality of life. Conclusions: This population-based study shows that skin diseases are very common in the rural areas of Nepal and have significant impact on quality of life. Targeted intervention at the primary health care level should help to reduce the health burden due to skin diseases.

Keywords: prevalence and pattern of skin diseases, impact on quality of life, rural Nepal, interventions

Procedia PDF Downloads 489
3677 Analysis of Different Classification Techniques Using WEKA for Diabetic Disease

Authors: Usama Ahmed

Abstract:

Data mining is the process of analyze data which are used to predict helpful information. It is the field of research which solve various type of problem. In data mining, classification is an important technique to classify different kind of data. Diabetes is most common disease. This paper implements different classification technique using Waikato Environment for Knowledge Analysis (WEKA) on diabetes dataset and find which algorithm is suitable for working. The best classification algorithm based on diabetic data is Naïve Bayes. The accuracy of Naïve Bayes is 76.31% and take 0.06 seconds to build the model.

Keywords: data mining, classification, diabetes, WEKA

Procedia PDF Downloads 147
3676 Dutch Disease and Industrial Development: An Investigation of the Determinants of Manufacturing Sector Performance in Nigeria

Authors: Kayode Ilesanmi Ebenezer Bowale, Dominic Azuh, Busayo Aderounmu, Alfred Ilesanmi

Abstract:

There has been a debate among scholars and policymakers about the effects of oil exploration and production on industrial development. In Nigeria, there were many reforms resulting in an increase in crude oil production in the recent past. There is a controversy on the importance of oil production in the development of the manufacturing sector in Nigeria. Some scholars claim that oil has been a blessing to the development of the manufacturing sector, while others regard it as a curse. The objective of the study is to determine if empirical analysis supports the presence of Dutch Disease and de-industrialisation in the Nigerian manufacturing sector between 2019- 2022. The study employed data that were sourced from World Development Indicators, Nigeria Bureau of Statistics, and the Central Bank of Nigeria Statistical Bulletin on manufactured exports, manufacturing employment, agricultural employment, and service employment in line with the theory of Dutch Disease using the unit root test to establish their level of stationarity, Engel and Granger cointegration test to check their long-run relationship. Autoregressive. Distributed Lagged bound test was also used. The Vector Error Correction Model will be carried out to determine the speed of adjustment of the manufacturing export and resource movement effect. The results showed that the Nigerian manufacturing industry suffered from both direct and indirect de-industrialisation over the period. The findings also revealed that there was resource movement as labour moved away from the manufacturing sector to both the oil sector and the services sector. The study concluded that there was the presence of Dutch Disease in the manufacturing industry, and the problem of de-industrialisation led to the crowding out of manufacturing output. The study recommends that efforts should be made to diversify the Nigerian economy. Furthermore, a conducive business environment should be provided to encourage more involvement of the private sector in the agriculture and manufacturing sectors of the economy.

Keywords: Dutch disease, resource movement, manufacturing sector performance, Nigeria

Procedia PDF Downloads 79
3675 Machine Learning-Driven Prediction of Cardiovascular Diseases: A Supervised Approach

Authors: Thota Sai Prakash, B. Yaswanth, Jhade Bhuvaneswar, Marreddy Divakar Reddy, Shyam Ji Gupta

Abstract:

Across the globe, there are a lot of chronic diseases, and heart disease stands out as one of the most perilous. Sadly, many lives are lost to this condition, even though early intervention could prevent such tragedies. However, identifying heart disease in its initial stages is not easy. To address this challenge, we propose an automated system aimed at predicting the presence of heart disease using advanced techniques. By doing so, we hope to empower individuals with the knowledge needed to take proactive measures against this potentially fatal illness. Our approach towards this problem involves meticulous data preprocessing and the development of predictive models utilizing classification algorithms such as Support Vector Machines (SVM), Decision Tree, and Random Forest. We assess the efficiency of every model based on metrics like accuracy, ensuring that we select the most reliable option. Additionally, we conduct thorough data analysis to reveal the importance of different attributes. Among the models considered, Random Forest emerges as the standout performer with an accuracy rate of 96.04% in our study.

Keywords: support vector machines, decision tree, random forest

Procedia PDF Downloads 40
3674 A Comparison of Convolutional Neural Network Architectures for the Classification of Alzheimer’s Disease Patients Using MRI Scans

Authors: Tomas Premoli, Sareh Rowlands

Abstract:

In this study, we investigate the impact of various convolutional neural network (CNN) architectures on the accuracy of diagnosing Alzheimer’s disease (AD) using patient MRI scans. Alzheimer’s disease is a debilitating neurodegenerative disorder that affects millions worldwide. Early, accurate, and non-invasive diagnostic methods are required for providing optimal care and symptom management. Deep learning techniques, particularly CNNs, have shown great promise in enhancing this diagnostic process. We aim to contribute to the ongoing research in this field by comparing the effectiveness of different CNN architectures and providing insights for future studies. Our methodology involved preprocessing MRI data, implementing multiple CNN architectures, and evaluating the performance of each model. We employed intensity normalization, linear registration, and skull stripping for our preprocessing. The selected architectures included VGG, ResNet, and DenseNet models, all implemented using the Keras library. We employed transfer learning and trained models from scratch to compare their effectiveness. Our findings demonstrated significant differences in performance among the tested architectures, with DenseNet201 achieving the highest accuracy of 86.4%. Transfer learning proved to be helpful in improving model performance. We also identified potential areas for future research, such as experimenting with other architectures, optimizing hyperparameters, and employing fine-tuning strategies. By providing a comprehensive analysis of the selected CNN architectures, we offer a solid foundation for future research in Alzheimer’s disease diagnosis using deep learning techniques. Our study highlights the potential of CNNs as a valuable diagnostic tool and emphasizes the importance of ongoing research to develop more accurate and effective models.

Keywords: Alzheimer’s disease, convolutional neural networks, deep learning, medical imaging, MRI

Procedia PDF Downloads 73
3673 Guillain Barre Syndrome in Children

Authors: A. Erragh, K. Amanzoui, M. Elharit, H. Salem, M. Ababneh, K. Elfakhr, S. Kalouch, A. Chlilek

Abstract:

Guillain-Barre syndrome (GBS) is the most common form of acute polyradiculoneuritis (PRNA). It is a medical emergency in pediatrics that requires rapid diagnosis and immediate assessment of the severity criteria for the implementation of appropriate treatment. Retrospective, descriptive study in 24 patients under the age of 18 who presented with GBS between September 2017 and July 2021 and were hospitalized in the multipurpose pediatric intensive care unit of the Abderrahim EL Harouchi children's hospital in Casablanca. The average age was 7.91 years, with extremes ranging from 18 months and 14 years and a male predominance of 75%. After a prodromal event, most often infectious (80%) and a free interval of 12 days on average, 2 types of motor disorders begin either hypo or arereflectic flaccid paralysis of the lower limbs (45.8%) or flaccid quadriplegia hypo or arereflectic (54.2%). During GBS, the most formidable complication is respiratory distress, which can occur at any time. In our study, respiratory impairment was observed in 70.8% of cases. In addition, other signs of severity, such as swallowing disorders (75%) and dysautonomic disorders (8.33%), were also observed, which justified care in the intensive care unit for all of our patients. The use of invasive ventilation was necessary in 76.5% of cases, and specific treatments based on immunoglobulins were administered in all our patients. Despite everything, the death rate remains high (25%) and is mainly due to complications related to hospitalization. Guillain Barré syndrome is, therefore, a pediatric emergency that requires rapid diagnosis and immediate assessment of severity criteria for the implementation of appropriate treatment.

Keywords: guillain barre syndrome, emergency, children, medical

Procedia PDF Downloads 71
3672 Proteomics Application in Disease Diagnosis and Reproduction İmprovement in Cow

Authors: Abdollah Sobhani, Hossein Vaseghi-Dodaran

Abstract:

Proteomics is defined as the study of the component of a cell, tissue and biological fluid. This technique has the potential to identify protein biomarkers of a disease states. In this study which was performed on bovine ovarian follicular cysts (BOFC), eight proteins are over expressed in BOFC that these proteins could be useful biomarkers for BOFC. The difference between serum proteome pattern cows affected by postpartum endometritis with healthy cows revealed that concentrations orosomucoid was decreased in endometritis. The comparison proteome of brucella abortus between laboratory adapted strains and clinical isolates could be useful to better understand this disease and vaccine development. Proteomics experiments identified new proteins and pathways that may be important in future hypothesis-driven studies of glucocorticoid-induced immunosuppression. Understanding the molecular mechanisms of effective parameters on male fertility is essential for obtaining high reproductive efficiency by decreasing cost and time. The investigations on proteome of high fertility spermatozoa indicated that expression of some proteins such as casein kinase 2 (CKII) prime poly peptide and tyrosine kinase in high fertility spermatozoa was higher compared to low fertility spermatozoa. Also, some evidence has indicated that variation in protein types and amounts in seminal fluid regulates fertility indexes in dairy bull. In conclusion, proteomics is a useful technique for discovering drugs, vaccine development, and diagnosis disease by biomarkers and improvement of reproduction efficiency.

Keywords: proteomics, reproduction, biomarker, immunity

Procedia PDF Downloads 412
3671 Correlative Study of Serum Interleukin-18 and Disease Activity, Functional Disability and Quality of Life in Rheumatoid Arthritis Patients

Authors: Hamdy Khamis Korayem, Manal Yehia Tayel, Abeer Shawky El Hadedy, Emmanuel Kamal Aziz Saba, Shimaa Badr Abdelnaby Badr

Abstract:

The aim of the current study was to demonstrate whether serum Interleukin-18 (IL-18) is increased in rheumatoid arthritis (RA) and its correlation with disease activity, functional disability and quality of life in RA patients. The study included 30 RA patients and 20 healthy normal control subjects. The RA patients were diagnosed according to the 2010 ACR/EULAR classification criteria for RA with the exclusion of those who had diabetes mellitus, endocrine disorders, associated rheumatologic diseases, viral hepatitis B or C and other diseases with increased serum IL-18 level. All patients were subjected to clinical evaluation of the musculoskeletal system. Disease activity was assessed by disease activity score 28 with 4 variables (DAS 28). Functional disability was assessed by health assessment questionnaire disability index (HAQ-DI). The quality of life was assessed by Short form-36 (SF-36) questionnaire. Radiological assessment of both hands and feet by Sharp/van der Heijde (SvH) scoring method. Laboratory parameters including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) were assessed in patients and serum level of IL-18 in both patients and control subjects. There was no statistically significant difference between patient and control group as regards age and sex. Among patients, 29 % were females and the age range was between 25 to 55 years. Extra-articular manifestations were presented in 56.7% of the patients. The mean of DAS 28 score was 5.73±1.46 and that of HAQ-DI was 1.22±0.72 while that of SF-36 was 40.03±13.96. The level of serum IL-18 was significantly higher in patients than in the control subjects (P= 0.030). Serum IL-18 was correlated with ACPA among the patient group. There were no statistically significant correlations between serum IL-18 and DAS28, HAQ-DI, SF-36, total SvH score and the other laboratory results. In conclusion, IL-18 is significantly higher in RA patient than in healthy control subjects and positively correlated with ACPA level. IL-18 is associated with extra-articular manifestations. However, it is not correlated with other laboratory parameters, disease activity, functional disability, quality of life nor radiological severity.

Keywords: disease activity score, Interleukin-18, quality of life assessment, rheumatoid arthritis

Procedia PDF Downloads 325
3670 Assessment of the Efficacy of Oral Vaccination of Wild Canids and Stray Dogs against Rabies in Azerbaijan

Authors: E. N. Hasanov, K. Y. Yusifova, M. A. Ali

Abstract:

Rabies is a zoonotic disease that causes acute encephalitis in domestic and wild carnivores. The goal of our investigation was to analyze the data on oral vaccination of wild canids and stray dogs in Azerbaijan. Before the start of the vaccination campaign conducted by the International Dialogue for Environmental Action (IDEA) Animal Care Center (IACC), all rabies cases in Azerbaijan for the period of 2017-2020 were analyzed. So, 30 regions for oral immunization with the Rabadrop vaccine were selected. In total, 95.9 thousand doses of baits were scattered in 30 regions, 970 (0.97%) remained intact. In addition, a campaign to sterilize and vaccinate stray dogs and cats undoubtedly had a positive impact on reducing the dynamics of rabies incidence. During the period 2017-2020, 2339 dogs and 2962 cats were sterilized and vaccinated under this program. It can be noted that the risk of rabies infection can be reduced through special preventive measures against disease reservoirs, which include oral immunization of wild and stray animals.

Keywords: rabies, vaccination, oral immunization, wild canids, stray dogs, baits, disease reservoirs

Procedia PDF Downloads 193
3669 Association of Ankle Brachial Index with Diabetic Score Neuropathy Examination in Type 2 Diabetes Melitus Patients

Authors: A. K. Putri, A.Fitri, C. A. Batubara

Abstract:

Diabetes Mellitus (DM) is a chronic disease that could cause complications. The complication can be Peripheral Arterial Disease (PAD) or Diabetic Neuropathy (DN). Peripheral Arterial Disease is checked by Ankle Brachial Index (ABI), DN is checked by Diabetic Neuropathy Examination (DNE) score. To determine the association of ABI and DNE score in DM type 2. This study uses a cross-sectional design. The subjects were DM patients at the neurology and endocrinology polyclinic at Haji Adam Malik Hospital Medan and its network hospital and this study subjects were examined for ABI and DNE scores. The data were analysed using the Fisher Exact statistics test. Demographics characteristic showed most of subject are female (51,6%), age range ≥ 60 (45.2% ; average 57,6 ± 9,8 years ), and history of DM 5-10 years (45,2%). The most patient ABI characteristics were mild PAD (42%) and moderate PAD (29%). The most patient DNE Score characteristics were≥ 3 (51,6%). There’s a significant relationship between ABI and DNE score in DM type 2 (p =0.016). Conclusion: There is a significant association between ABI and DNE scores in DM type 2 patients

Keywords: diabetic neuropathy, diabetes mellitus, ankle-brachial index, diabetic neuropathy examination

Procedia PDF Downloads 113
3668 Automatic Classification of Lung Diseases from CT Images

Authors: Abobaker Mohammed Qasem Farhan, Shangming Yang, Mohammed Al-Nehari

Abstract:

Pneumonia is a kind of lung disease that creates congestion in the chest. Such pneumonic conditions lead to loss of life of the severity of high congestion. Pneumonic lung disease is caused by viral pneumonia, bacterial pneumonia, or Covidi-19 induced pneumonia. The early prediction and classification of such lung diseases help to reduce the mortality rate. We propose the automatic Computer-Aided Diagnosis (CAD) system in this paper using the deep learning approach. The proposed CAD system takes input from raw computerized tomography (CT) scans of the patient's chest and automatically predicts disease classification. We designed the Hybrid Deep Learning Algorithm (HDLA) to improve accuracy and reduce processing requirements. The raw CT scans have pre-processed first to enhance their quality for further analysis. We then applied a hybrid model that consists of automatic feature extraction and classification. We propose the robust 2D Convolutional Neural Network (CNN) model to extract the automatic features from the pre-processed CT image. This CNN model assures feature learning with extremely effective 1D feature extraction for each input CT image. The outcome of the 2D CNN model is then normalized using the Min-Max technique. The second step of the proposed hybrid model is related to training and classification using different classifiers. The simulation outcomes using the publically available dataset prove the robustness and efficiency of the proposed model compared to state-of-art algorithms.

Keywords: CT scan, Covid-19, deep learning, image processing, lung disease classification

Procedia PDF Downloads 155
3667 The Interaction between Blood-Brain Barrier and the Cerebral Lymphatics Proposes Therapeutic Method for Alzheimer’S Disease

Authors: M. Klimova, O. Semyachkina-Glushkovskaya, J. Kurts, E. Zinchenko, N. Navolokin, A. Shirokov, A. Dubrovsky, A. Abdurashitov, A. Terskov, A. Mamedova, I. Agranovich, T. Antonova, I. Blokhina

Abstract:

The direction for research of Alzheimer's disease is to find an effective non-invasive and non-pharmacological way of treatment. Here we tested our hypothesis that the opening of the blood-brain barrier (BBB) induces activation of lymphatic drainage and clearing functions that can be used as a method for non-invasive stimulation of clearance of beta-amyloid and therapy of Alzheimer’s disease (AD). To test our hypothesis, in this study on healthy male mice we analyzed the interaction between BBB opening by repeated loud music (100-10000 Hz, 100 dB, duration 2 h: 60 sec – sound; 60 sec - pause) and functional changes in the meningeal lymphatic vessels (MLVs). We demonstrate clearance of dextran 70 kDa (i.v. injection), fluorescent beta-amyloid (intrahippocampal injection) and gold nanorods (intracortical injection) via MLV that significantly increased after the opening of BBB. Our studies also demonstrate that the BBB opening was associated with the improvement of neurocognitive status in mice with AD. Thus, we uncover therapeutic effects of BBB opening by loud music, such as non-invasive stimulation of lymphatic clearance of beta-amyloid in mice with AD, accompanied by improvement of their neurocognitive status. Our data are consistent with other results suggesting the therapeutic effect of BBB opening by focused ultrasound without drugs for patients with AD. This research was supported by a grant from RSF 18-75-10033

Keywords: Alzheimer's disease, beta-amyloid, blood-brain barrier, meningeal lymphatic vessels, repeated loud music

Procedia PDF Downloads 142
3666 Comparison of Deep Brain Stimulation Targets in Parkinson's Disease: A Systematic Review

Authors: Hushyar Azari

Abstract:

Aim and background: Deep brain stimulation (DBS) is regarded as an important therapeutic choice for Parkinson's disease (PD). The two most common targets for DBS are the subthalamic nucleus (STN) and globus pallidus (GPi). This review was conducted to compare the clinical effectiveness of these two targets. Methods: A systematic literature search in electronic databases: Embase, Cochrane Library and PubMed were restricted to English language publications 2010 to 2021. Specified MeSH terms were searched in all databases. Studies which evaluated the Unified Parkinson's Disease Rating Scale (UPDRS) III were selected by meeting the following criteria: (1) compared both GPi and STN DBS; (2) had at least three months follow-up period; (3)at least five participants in each group; (4)conducted after 2010. Study quality assessment was performed using the Modified Jadad Scale. Results: 3577 potentially relevant articles were identified, of these, 3569 were excluded based on title and abstract, duplicate and unsuitable article removal. Eight articles satisfied the inclusion criteria and were scrutinized (458 PD patients). According to Modified Jadad Scale, the majority of included studies had low evidence quality which was a limitation of this review. 5 studies reported no statistically significant between-group difference for improvements in UPDRS ш scores. At the same time, there were some results in terms of pain, action tremor, rigidity, and urinary symptoms, which indicated that STN DBS might be a better choice. Regarding the adverse effects, GPi was superior. Conclusion: It is clear that other larger randomized clinical trials with longer follow-up periods and control groups are needed to decide which target is more efficient for deep brain stimulation in Parkinson’s disease and imposes fewer adverse effects on the patients. Meanwhile, STN seems more reasonable according to the results of this systematic review.

Keywords: brain stimulation, globus pallidus, Parkinson's disease, subthalamic nucleus

Procedia PDF Downloads 179
3665 Using Wearable Device with Neuron Network to Classify Severity of Sleep Disorder

Authors: Ru-Yin Yang, Chi Wu, Cheng-Yu Tsai, Yin-Tzu Lin, Wen-Te Liu

Abstract:

Background: Sleep breathing disorder (SDB) is a condition demonstrated by recurrent episodes of the airway obstruction leading to intermittent hypoxia and quality fragmentation during sleep time. However, the procedures for SDB severity examination remain complicated and costly. Objective: The objective of this study is to establish a simplified examination method for SDB by the respiratory impendence pattern sensor combining the signal processing and machine learning model. Methodologies: We records heart rate variability by the electrocardiogram and respiratory pattern by impendence. After the polysomnography (PSG) been done with the diagnosis of SDB by the apnea and hypopnea index (AHI), we calculate the episodes with the absence of flow and arousal index (AI) from device record. Subjects were divided into training and testing groups. Neuron network was used to establish a prediction model to classify the severity of the SDB by the AI, episodes, and body profiles. The performance was evaluated by classification in the testing group compared with PSG. Results: In this study, we enrolled 66 subjects (Male/Female: 37/29; Age:49.9±13.2) with the diagnosis of SDB in a sleep center in Taipei city, Taiwan, from 2015 to 2016. The accuracy from the confusion matrix on the test group by NN is 71.94 %. Conclusion: Based on the models, we established a prediction model for SDB by means of the wearable sensor. With more cases incoming and training, this system may be used to rapidly and automatically screen the risk of SDB in the future.

Keywords: sleep breathing disorder, apnea and hypopnea index, body parameters, neuron network

Procedia PDF Downloads 150
3664 The Role of Critical Thinking in Disease Diagnosis: A Comprehensive Review

Authors: Mohammad Al-Mousawi

Abstract:

This academic article explores the indispensable role of critical thinking in the process of diagnosing diseases. Employing a multidisciplinary approach, we delve into the cognitive skills and analytical mindset that clinicians, researchers, and healthcare professionals must employ to navigate the complexities of disease identification. By examining the integration of critical thinking within the realms of medical education, diagnostic decision-making, and technological advancements, this article aims to underscore the significance of cultivating and applying critical thinking skills in the ever-evolving landscape of healthcare.

Keywords: critical thinking, medical education, diagnostic decision-making, fostering critical thinking

Procedia PDF Downloads 74
3663 Brown-Spot Needle Blight: An Emerging Threat Causing Loblolly Pine Needle Defoliation in Alabama, USA

Authors: Debit Datta, Jeffrey J. Coleman, Scott A. Enebak, Lori G. Eckhardt

Abstract:

Loblolly pine (Pinus taeda) is a leading productive timber species in the southeastern USA. Over the past three years, an emerging threat is expressed by successive needle defoliation followed by stunted growth and tree mortality in loblolly pine plantations. Considering economic significance, it has now become a rising concern among landowners, forest managers, and forest health state cooperators. However, the symptoms of the disease were perplexed somewhat with root disease(s) and recurrently attributed to invasive Phytophthora species due to the similarity of disease nature and devastation. Therefore, the study investigated the potential causal agent of this disease and characterized the fungi associated with loblolly pine needle defoliation in the southeastern USA. Besides, 70 trees were selected at seven long-term monitoring plots at Chatom, Alabama, to monitor and record the annual disease incidence and severity. Based on colony morphology and ITS-rDNA sequence data, a total of 28 species of fungi representing 17 families have been recovered from diseased loblolly pine needles. The native brown-spot pathogen, Lecanosticta acicola, was the species most frequently recovered from unhealthy loblolly pine needles in combination with some other common needle cast and rust pathogen(s). Identification was confirmed using morphological similarity and amplification of translation elongation factor 1-alpha gene region of interest. Tagged trees were consistently found chlorotic and defoliated from 2019 to 2020. The current emergence of the brown-spot pathogen causing loblolly pine mortality necessitates the investigation of the role of changing climatic conditions, which might be associated with increased pathogen pressure to loblolly pines in the southeastern USA.

Keywords: brown-spot needle blight, loblolly pine, needle defoliation, plantation forestry

Procedia PDF Downloads 152
3662 Nontuberculous Mycobacterium Infection – Still An Important Disease Among People With Late HIV Diagnosis

Authors: Jakub Młoźniak, Adam Szymański, Gabriela Stondzik, Dagny Krankowska, Tomasz Mikuła

Abstract:

Nontuberculous mycobacteria (NTM) are bacterial species that cause diversely manifesting diseases mainly in immunocompromised patients. In people with HIV, NTM infection is an AIDS-defining disease and usually appears when the lymphocyte T CD4 count is below 50 cells/μl. The usage of antiretroviral therapy has decreased the prevalence of NTM among people with HIV, but the disease can still be observed especially among patients with late HIV diagnosis. Common presence in environment, human colonization, clinical similarity with tuberculosis and slow growth on culture makes NTM especially hard to diagnose. The study aimed to analyze the epidemiology and clinical course of NTM among patients with HIV. This study included patients with NTM and HIV admitted to our department between 2017 and 2023. Medical records of patients were analyzed and data on age, sex, median time from HIV diagnosis to identification of NTM infection, median CD4 count at NTM diagnosis, methods of determining NTM infection, type of species of mycobacteria identified, clinical symptoms and treatment course were gathered. Twenty-four patients (20 men, 4 women) with identified NTM were included in this study. Among them, 20 were HIV late presenters. The patients' median age was 40. The main symptoms which patients presented were fever, weight loss and cough. Pulmonary disease confirmed with positive cultures from sputum/bronchoalveolar lavage was present in 18 patients. M. avium was the most common species identified. M. marinum caused disseminated skin lesions in 1 patient. Out of all, 5 people were not treated for NTM caused by lack of symptoms and suspicion of colonization with mycobacterium. Concomitant tuberculosis was present in 6 patients. The median diagnostic time from HIV to NTM infections was 3.5 months. The median CD4 count at NTM identification was 69.5 cells/μl. Median NTM treatment time was 16 months but 7 patients haven’t finished their treatment yet. The most commonly used medications were ethambutol and clarithromycin. Among analyzed patients, 4 of them have died. NTM infections are still an important disease among patients who are HIV late presenters. This disease should be taken into consideration during the differential diagnosis of fever, weight loss and cough in people with HIV with lymphocyte T CD4 count <100 cells/μl. Presence of tuberculosis does not exclude nontuberculous mycobacterium coinfection.

Keywords: mycobacteriosis, HIV, late presenter, epidemiology

Procedia PDF Downloads 42
3661 Structure-Guided Optimization of Sulphonamide as Gamma–Secretase Inhibitors for the Treatment of Alzheimer’s Disease

Authors: Vaishali Patil, Neeraj Masand

Abstract:

In older people, Alzheimer’s disease (AD) is turning out to be a lethal disease. According to the amyloid hypothesis, aggregation of the amyloid β–protein (Aβ), particularly its 42-residue variant (Aβ42), plays direct role in the pathogenesis of AD. Aβ is generated through sequential cleavage of amyloid precursor protein (APP) by β–secretase (BACE) and γ–secretase (GS). Thus in the treatment of AD, γ-secretase modulators (GSMs) are potential disease-modifying as they selectively lower pathogenic Aβ42 levels by shifting the enzyme cleavage sites without inhibiting γ–secretase activity. This possibly avoids known adverse effects observed with complete inhibition of the enzyme complex. Virtual screening, via drug-like ADMET filter, QSAR and molecular docking analyses, has been utilized to identify novel γ–secretase modulators with sulphonamide nucleus. Based on QSAR analyses and docking score, some novel analogs have been synthesized. The results obtained by in silico studies have been validated by performing in vivo analysis. In the first step, behavioral assessment has been carried out using Scopolamine induced amnesia methodology. Later the same series has been evaluated for neuroprotective potential against the oxidative stress induced by Scopolamine. Biochemical estimation was performed to evaluate the changes in biochemical markers of Alzheimer’s disease such as lipid peroxidation (LPO), Glutathione reductase (GSH), and Catalase. The Scopolamine induced amnesia model has shown increased Acetylcholinesterase (AChE) levels and the inhibitory effect of test compounds in the brain AChE levels have been evaluated. In all the studies Donapezil (Dose: 50µg/kg) has been used as reference drug. The reduced AChE activity is shown by compounds 3f, 3c, and 3e. In the later stage, the most potent compounds have been evaluated for Aβ42 inhibitory profile. It can be hypothesized that this series of alkyl-aryl sulphonamides exhibit anti-AD activity by inhibition of Acetylcholinesterase (AChE) enzyme as well as inhibition of plaque formation on prolong dosage along with neuroprotection from oxidative stress.

Keywords: gamma-secretase inhibitors, Alzzheimer's disease, sulphonamides, QSAR

Procedia PDF Downloads 255