Search results for: cardiovascular disease
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4003

Search results for: cardiovascular disease

3523 MR Imaging Spectrum of Intracranial Infections: An Experience of 100 Cases in a Tertiary Hospital in Northern India

Authors: Avik Banerjee, Kavita Saggar

Abstract:

Infections of the nervous system and adjacent structures are often life-threatening conditions. Despite the recent advances in neuroimaging evaluation, the diagnosis of unclear infectious CNS disease remains a challenge. Our aim is to evaluate the typical and atypical neuro-imaging features of the various routinely encountered CNS infected patients so as to form guidelines for their imaging recognition and differentiation from tumoral, vascular and other entities that warrant a different line of therapy.

Keywords: central nervous system (CNS), Cerebro Spinal Fluid (Csf), Creutzfeldt Jakob Disease (CJD), progressive multifocal leukoencephalopathy (PML)

Procedia PDF Downloads 275
3522 The GRIT Study: Getting Global Rare Disease Insights Through Technology Study

Authors: Aneal Khan, Elleine Allapitan, Desmond Koo, Katherine-Ann Piedalue, Shaneel Pathak, Utkarsh Subnis

Abstract:

Background: Disease management of metabolic, genetic disorders is long-term and can be cumbersome to patients and caregivers. Patient-Reported Outcome Measures (PROMs) have been a useful tool in capturing patient perspectives to help enhance treatment compliance and engagement with health care providers, reduce utilization of emergency services, and increase satisfaction with their treatment choices. Currently, however, PROMs are collected during infrequent and decontextualized clinic visits, which makes translation of patient experiences challenging over time. The GRIT study aims to evaluate a digital health journal application called Zamplo that provides a personalized health diary to record self-reported health outcomes accurately and efficiently in patients with metabolic, genetic disorders. Methods: This is a randomized controlled trial (RCT) (1:1) that assesses the efficacy of Zamplo to increase patient activation (primary outcome), improve healthcare satisfaction and confidence to manage medications (secondary outcomes), and reduce costs to the healthcare system (exploratory). Using standardized online surveys, assessments will be collected at baseline, 1 month, 3 months, 6 months, and 12 months. Outcomes will be compared between patients who were given access to the application versus those with no access. Results: Seventy-seven patients were recruited as of November 30, 2021. Recruitment for the study commenced in November 2020 with a target of n=150 patients. The accrual rate was 50% from those eligible and invited for the study, with the majority of patients having Fabry disease (n=48) and the remaining having Pompe disease and mitochondrial disease. Real-time clinical responses, such as pain, are being measured and correlated to disease-modifying therapies, supportive treatments like pain medications, and lifestyle interventions. Engagement with the application, along with compliance metrics of surveys and journal entries, are being analyzed. An interim analysis of the engagement data along with preliminary findings from this pilot RCT, and qualitative patient feedback will be presented. Conclusions: The digital self-care journal provides a unique approach to disease management, allowing patients direct access to their progress and actively participating in their care. Findings from the study can help serve the virtual care needs of patients with metabolic, genetic disorders in North America and the world over.

Keywords: eHealth, mobile health, rare disease, patient outcomes, quality of life (QoL), pain, Fabry disease, Pompe disease

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3521 Brain Atrophy in Alzheimer's Patients

Authors: Tansa Nisan Gunerhan

Abstract:

Dementia comes in different forms, including Alzheimer's disease. The most common dementia diagnosis among elderly individuals is Alzheimer's disease. On average, for patients with Alzheimer’s, life expectancy is around 4-8 years after the diagnosis; however, expectancy can go as high as twenty years or more, depending on the shrinkage of the brain. Normally, along with aging, the brain shrinks at some level but doesn’t lose a vast amount of neurons. However, Alzheimer's patients' neurons are destroyed rapidly; hence problems with loss of memory, communication, and other metabolic activities begin. The toxic changes in the brain affect the stability of the neurons. Beta-amyloid and tau are two proteins that are believed to play a role in the development of Alzheimer's disease through their toxic changes. Beta-amyloid is a protein that is produced in the brain and is normally broken down and removed from the body. However, in people with Alzheimer's disease, the production of beta-amyloid increases, and it begins to accumulate in the brain. These plaques are thought to disrupt communication between nerve cells and may contribute to the death of brain cells. Tau is a protein that helps to stabilize microtubules, which are essential for the transportation of nutrients and other substances within brain cells. In people with Alzheimer's disease, tau becomes abnormal and begins to accumulate inside brain cells, forming neurofibrillary tangles. These tangles disrupt the normal functioning of brain cells and may contribute to their death, forming amyloid plaques which are deposits of a protein called amyloid-beta that build up between nerve cells in the brain. The accumulation of amyloid plaques and neurofibrillary tangles in the brain is thought to contribute to the shrinkage of brain tissue. As the brain shrinks, the size of the brain may decrease, leading to a reduction in brain volume. Brain atrophy in Alzheimer's disease is often accompanied by changes in the structure and function of brain cells and the connections between them, leading to a decline in brain function. These toxic changes that accumulate can cause symptoms such as memory loss, difficulty with thinking and problem-solving, and changes in behavior and personality.

Keywords: Alzheimer, amyloid-beta, brain atrophy, neuron, shrinkage

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3520 A Case Report on Diaphragm Disease of Small Bowel Following Usage of Non-Steroidal Anti-Inflammatory Drugs

Authors: Shivani Kuttuva, Bridget Fergie, Andrew Mishreki, Shovkat Mir, Fintan Bergin

Abstract:

Diaphragm disease (DD) of the small bowel is a condition wherein the bowel lumen is divided into a series of short compartments by multiple circumferential membranes of mucosa and submucosa, leading to pinhole lumen and subsequent obstruction. It is a rare condition commonly attributed to non-steroidal anti-inflammatory drugs (NSAIDs) usage. Herein we present a 31-yr-old-female with a history of NSAIDs usage for one year following neurosurgery, who presented with recurrent idiopathic small bowel obstruction, recalcitrant anaemia, and impaction of capsule endoscope on investigating for anaemia. The capsule endoscopy images demonstrated multiple circumferential strictures with ulcers at its tip and villous atrophy in the proximal bowel, suggestive of NSAIDs related damage. However, due to the lack of awareness of the detrimental effects of NSAIDs on bowel mucosa distal to the duodenum, the underlying aetiology of this clinical presentation remained a mystery for a significant duration. The patient had to undergo repeated laparotomies in order to relieve the symptoms of recurring acute small bowel obstruction. Upon examining the resected specimen under microscopy, the histopathological hallmark of expanded, fibrotic, and congested submucosa was picked up, leading to the confirmation of diaphragm disease. Thus, this case report aims to widen the awareness among clinicians and aid surgeons in devising a management plan for young individuals presenting with recurring episodes of obstruction due to Diaphragm disease.

Keywords: capsule endoscopy, diaphragm disease, NSAIDs, recurrent small bowel obstruction

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3519 Cost-Effective and Optimal Control Analysis for Mitigation Strategy to Chocolate Spot Disease of Faba Bean

Authors: Haileyesus Tessema Alemneh, Abiyu Enyew Molla, Oluwole Daniel Makinde

Abstract:

Introduction: Faba bean is one of the most important grown plants worldwide for humans and animals. Several biotic and abiotic elements have limited the output of faba beans, irrespective of their diverse significance. Many faba bean pathogens have been reported so far, of which the most important yield-limiting disease is chocolate spot disease (Botrytis fabae). The dynamics of disease transmission and decision-making processes for intervention programs for disease control are now better understood through the use of mathematical modeling. Currently, a lot of mathematical modeling researchers are interested in plant disease modeling. Objective: In this paper, a deterministic mathematical model for chocolate spot disease (CSD) on faba bean plant with an optimal control model was developed and analyzed to examine the best strategy for controlling CSD. Methodology: Three control interventions, quarantine (u2), chemical control (u3), and prevention (u1), are employed that would establish the optimal control model. The optimality system, characterization of controls, the adjoint variables, and the Hamiltonian are all generated employing Pontryagin’s maximum principle. A cost-effective approach is chosen from a set of possible integrated strategies using the incremental cost-effectiveness ratio (ICER). The forward-backward sweep iterative approach is used to run numerical simulations. Results: The Hamiltonian, the optimality system, the characterization of the controls, and the adjoint variables were established. The numerical results demonstrate that each integrated strategy can reduce the diseases within the specified period. However, due to limited resources, an integrated strategy of prevention and uprooting was found to be the best cost-effective strategy to combat CSD. Conclusion: Therefore, attention should be given to the integrated cost-effective and environmentally eco-friendly strategy by stakeholders and policymakers to control CSD and disseminate the integrated intervention to the farmers in order to fight the spread of CSD in the Faba bean population and produce the expected yield from the field.

Keywords: CSD, optimal control theory, Pontryagin’s maximum principle, numerical simulation, cost-effectiveness analysis

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3518 High-Resolution ECG Automated Analysis and Diagnosis

Authors: Ayad Dalloo, Sulaf Dalloo

Abstract:

Electrocardiogram (ECG) recording is prone to complications, on analysis by physicians, due to noise and artifacts, thus creating ambiguity leading to possible error of diagnosis. Such drawbacks may be overcome with the advent of high resolution Methods, such as Discrete Wavelet Analysis and Digital Signal Processing (DSP) techniques. This ECG signal analysis is implemented in three stages: ECG preprocessing, features extraction and classification with the aim of realizing high resolution ECG diagnosis and improved detection of abnormal conditions in the heart. The preprocessing stage involves removing spurious artifacts (noise), due to such factors as muscle contraction, motion, respiration, etc. ECG features are extracted by applying DSP and suggested sloping method techniques. These measured features represent peak amplitude values and intervals of P, Q, R, S, R’, and T waves on ECG, and other features such as ST elevation, QRS width, heart rate, electrical axis, QR and QT intervals. The classification is preformed using these extracted features and the criteria for cardiovascular diseases. The ECG diagnostic system is successfully applied to 12-lead ECG recordings for 12 cases. The system is provided with information to enable it diagnoses 15 different diseases. Physician’s and computer’s diagnoses are compared with 90% agreement, with respect to physician diagnosis, and the time taken for diagnosis is 2 seconds. All of these operations are programmed in Matlab environment.

Keywords: ECG diagnostic system, QRS detection, ECG baseline removal, cardiovascular diseases

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3517 Phylogenetic Analyses of Newcastle Disease Virus Isolated from Unvaccinated Chicken Flocks in Kyrgyzstan from 2015 to 2016

Authors: Giang Tran Thi Huong, Hieu Dong Van, Tung Dao Duy, Saadanov Iskender, Isakeev Mairambek, Tsutomu Omatsu, Yukie Katayama, Tetsuya Mizutani, Yuki Ozeki, Yohei Takeda, Haruko Ogawa, Kunitoshi Imai

Abstract:

Newcastle disease virus (NDV) is a contagious viral disease of the poultry industry and other birds throughout the world. At present, very little is known about molecular epidemiological data regarding the causes of ND outbreak in commercial poultry farms in Kyrgyzstan. In the current study, the NDV isolated from the one out of three samples from the unvaccinated flock was confirmed as NDV. Phylogenetic analysis indicated that this NDV strain is clustered in the Class II subgenotype VIId, and closely related to the Chinese NDV isolate. Phylogenetic analyses revealed that the isolated NDV strain has an origin different from the 4 NDV strains previously identified in Kyrgyzstan. According to the mean death time (MDT: 61.1 h) and a multibasic amino acid (aa) sequence at the F0 proteolytic cleavage site (¹¹²R-R-Q-K-R-F¹¹⁷), the NDV isolate was determined as mesogenic strain. Several mutations in the neutralizing epitopes (notably, ³⁴⁷E→K) and the global head were observed in the hemagglutinin-neuraminidase (HN) protein of the current isolate. The present study represents the molecular characterization of the coding gene region of NDV in Kyrgyzstan. Additionally, further study will be investigated on the antigenic characterization using monoclonal antibody.

Keywords: Kyrgyzstan, Newcastle disease, genotype, genome characterization

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3516 Relationship of Silent Myocardial Ischemia to Erectile Dysfunction in Patients with Diabetes Mellitus

Authors: Ali Kassem, Esam Nada, Amro Abdelhamed, Shigeo Horie

Abstract:

Objective: Diabetes mellitus (DM) is associated with macrovascular complications, including coronary artery disease (CAD), and microvascular complications that contribute to the pathogenesis of erectile dysfunction (ED). On the other hand, silent myocardial ischemia (SMI) is more common in diabetic patients and is a strong predictor of cardiac events and mortality in diabetic and non-diabetic patients. Recently, Multidetector computed tomographic coronary angiography (MDCT-CA) has become a reliable non-invasive imaging modality for screening diabetic patients for SMI. We aim to evaluate the presence of SMI using (MDCT-CA) in patients with type 2DM having ED. Methods: This study evaluated 20 patients (mean age 61.45 ± 10.7 years), with DM and ED without any history of angina or angina equivalent. ED was tested with the Sexual Health Inventory for Men score, erection hardness score (EHS), and maximal penile circumferential change by an erect meter. Results: Of twenty studied patients, coronary artery stenosis was detected in 13 (65%) patients in the form of one-vessel disease (n = 6, 30%), two-vessel disease (n = 2, 10%), and three-vessel disease (n = 5, 25%). Maximum coronary artery stenosis was positively correlated with age (P < 0.016,) and negatively correlated with EHS (P <04). Multivariate regression analysis using age and EHS showed that age was the only independent predictor of SMI (P <04). Conclusion: MDCT-CA is a useful tool to identify SMI in patients with diabetes mellitus and ED. One should consider the possibility of SMI especially in elderly patients with DM who have ED.

Keywords: diabetes mellitus, erectile dysfunction, microvascular, silent ischemia

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3515 Design of an Active Compression System for Treating Vascular Disease Using a Series of Silicone Based Inflatable Mini Bladders

Authors: Gayani K. Nandasiri, Tilak Dias, William Hurley

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Venous disease of human lower limb could range from minor asymptomatic incompetence of venous valves to chronic venous ulceration. The sheer prevalence of varicose veins and its associated significant costs of treating late complications such as chronic ulcers contribute to a higher burden on health care resources. In most of western countries with developed health care systems, treatment costs associated with Venous disease accounts for a considerable portion of their total health care budget, and it has become a high-cost burden to National Health Service (NHS), UK. The established gold standard of treatment for the venous disease is the graduated compression, where the pressure at the ankle being highest and decreasing towards the knee and thigh. Currently, medical practitioners use two main methods to treat venous disease; i.e. compression bandaging and compression stockings. Both these systems have their own disadvantages which lead to the current programme of research. The aim of the present study is to revolutionize the compression therapy by using a novel active compression system to deliver a controllable and more accurate pressure profiles using a series of inflatable mini bladders. Two types of commercially available silicones were tested for the application. The mini bladders were designed with a special fabrication procedure to provide required pressure profiles, and a series of experiments were conducted to characterise the mini bladders. The inflation/deflation heights of these mini bladders were investigated experimentally and using a finite element model (FEM), and the experimental data were compared to the results obtained from FEM simulations, which showed 70-80% agreement. Finally, the mini bladders were tested for its pressure transmittance characteristics, and the results showed a 70-80% of inlet air pressure transmitted onto the treated surface.

Keywords: finite element analysis, graduated compression, inflatable bladders, venous disease

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3514 Identification of Significant Genes in Rheumatoid Arthritis, Melanoma Metastasis, Ulcerative Colitis and Crohn’s Disease

Authors: Krishna Pal Singh, Shailendra Kumar Gupta, Olaf Wolkenhauer

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Background: Our study aimed to identify common genes and potential targets across the four diseases, which include rheumatoid arthritis, melanoma metastasis, ulcerative colitis, and Crohn’s disease. We used a network and systems biology approach to identify the hub gene, which can act as a potential target for all four disease conditions. The regulatory network was extracted from the PPI using the MCODE module present in Cytoscape. Our objective was to investigate the significance of hub genes in these diseases using gene ontology and KEGG pathway enrichment analysis. Methods: Our methodology involved collecting disease gene-related information from DisGeNET databases and performing protein-protein interaction (PPI) network and core genes screening. We then conducted gene ontology and KEGG pathway enrichment analysis. Results: We found that IL6 plays a critical role in all disease conditions and in different pathways that can be associated with the development of all four diseases. Conclusions: The theoretical importance of our research is that we employed various systems and structural biology techniques to identify a crucial protein that could serve as a promising target for treating multiple diseases. Our data collection and analysis procedures involved rigorous scrutiny, ensuring high-quality results. Our conclusion is that IL6 plays a significant role in all four diseases, and it can act as a potential target for treating them. Our findings may have important implications for the development of novel therapeutic interventions for these diseases.

Keywords: melanoma metastasis, rheumatoid arthritis, inflammatory bowel diseases, integrated bioinformatics analysis

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3513 Neuroprotective Effects of Dehydroepiandrosterone (DHEA) in Rat Model of Alzheimer’s Disease

Authors: Hanan F. Aly, Fateheya M. Metwally, Hanaa H. Ahmed

Abstract:

The current study is undertaken to elucidate a possible neuroprotective role of dehydroepiandrosterone (DHEA) against the development of Alzheimer’s disease in experimental rat model. Alzheimer’s disease was produced in young female ovariectomized rats by intraperitoneal administration of AlCl3 (4.2 mg/kg body weight) daily for 12 weeks. Half of these animals also received orally DHEA (250 mg/kg body weight, three times weekly) for 18 weeks. Control groups of animals received either DHAE alone, or no DHEA, or were not ovariectomized. After such treatment the animals were analyzed for oxidative stress biomarkers such as hydrogen peroxide, nitric oxide and malondialdehyde, total antioxidant capacity, reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase activities, antiapoptotic marker Bcl-2 and brain derived neurotrophic factor. Also, brain cholinergic markers (acetylcholinesterase and acetylcholine) were determined. The results revealed significant increase in oxidative stress parameters associated with significant decrease in the antioxidant enzyme activities in Al-intoxicated ovariectomized rats. Significant depletion in brain Bcl-2 and brain-derived neurotrophic factor levels were also detected. Moreover, significant elevations in brain acetylcholinesterase activity accompanied with significant reduction in acetylcholine level were recorded. Significant amelioration in all investigated parameters was detected as a result of treatment of Al-intoxicated ovariectomized rats with DHEA. These results were confirmed by histological examination of brain sections. These results clearly indicate a neuroprotective effect of DHEA against Alzheimer’s disease.

Keywords: Alzheimer’s disease, oxidative stress, apoptosis, dehydroepiandrosterone

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3512 Hepatitis B Vaccination Status and Its Determinants among Primary Health Care Workers in Northwest Pakistan

Authors: Mohammad Tahir Yousafzai, Rubina Qasim

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We assessed Hepatitis B vaccination and its determinants among health care workers (HCW) in Northwest Pakistan. HCWs from both public and private clinics were interviewed about hepatitis B vaccination, socio-demographic, hepatitis B virus transmission modes, disease threat and benefits of vaccination. Logistic regression was performed. Hepatitis B vaccination was 40% (Qualified Physicians: 86% and non-qualified Dispensers:16%). Being Qualified Physician (Adj. OR 26.6; 95%CI 9.3-73.2), Non-qualified Physician (Adj.OR 1.9; 95%CI 0.8-4.6), qualified Dispensers (Adj. OR 3.6; 95%CI 1.3-9.5) compared to non-qualified Dispensers, working in public clinics (Adj. OR 2.5; 95%CI 1.1-5.7) compared to private, perceived disease threat after exposure to blood and body fluids (Adj. OR 1.1; 95%CI 1.1-1.2) and perceived benefits of vaccination (Adj. OR 1.1; 95%CI 1.1-1.2) were significant predictors of hepatitis B vaccination. Improved perception of disease threat and benefits of vaccination and qualification of HCWs are associated with hepatitis B vaccination.

Keywords: Hepatitis B vaccine, immunization, healthcare workers, primary health

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3511 The Relationship between Physical Fitness and Academic Performance among University Students

Authors: Bahar Ayberk

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The study was conducted to determine the relationship between physical fitness and academic performance among university students. A far-famed saying ‘Sound mind in a sound body’ referring to the potential quality of increased physical fitness in the intellectual development of individuals seems to be endorsed. There is a growing body of literature the impact of physical fitness on academic achievement, especially in elementary and middle-school aged children. Even though there are numerous positive effects related to being physically active and physical fitness, their effect on academic achievement is not very much clear for university students. The subjects for this study included 25 students (20 female and 5 male) enrolled in Yeditepe University, Physiotherapy and Rehabilitation Department of Health Science Faculty. All participants filled in a questionnaire about their socio-demographic status, general health status, and physical activity status. Health-related physical fitness testing, included several core components: 1) body composition evaluation (body mass index, waist-to-hip ratio), 2) cardiovascular endurance evaluation (queen’s college step test), 3) muscle strength and endurance evaluation (sit-up test, push-up test), 4) flexibility evaluation (sit and reach test). Academic performance evaluation was based on student’s Cumulative Grade Point Average (CGPA). The prevalence of the subjects participating physical activity was found to be 40% (n = 10). CGPA scores were significantly higher among students having regular physical activity when we compared the students having regular physical activities or not (respectively 2,71 ± 0.46, 3.02 ± 0.28 scores, p = 0.076). The result of the study also revealed that there is positive correlation relationship between sit-up, push up and academic performance points (CGPA) (r = 0.43, p ≤ 0.05 ) and negative correlation relationship between cardiovascular endurance parameter (Queen's College Step Test) and academic performance points (CGPA) (r = -0.47, p ≤ 0.05). In conclusion, the findings confirmed that physical fitness level was generally associated with academic performance in the study group. Cardiovascular endurance and muscle strength and endurance were associated with student’s CGPA, whereas body composition and flexibility were unrelated to CGPA.

Keywords: academic performance, health-related physical fitness, physical activity, physical fitness testing

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3510 Projected Impact of Population Aging on Noncommunicable Disease Burden and Costs in the Kingdom of Saudi Arabia, 2020–2030

Authors: David C. Boettiger, Tracy Kuo Lin, Maram Almansour, Mariam M. Hamza, Reem Alsukait, Christopher H. Herbst, Nada Altheyab, Ayman Afghani, Faisal Kattan

Abstract:

Background The number of people aged greater than 65 years per 100 people aged 20–64 years is expected to almost double in The Kingdom of Saudi Arabia (KSA) between 2020 and 2030. We therefore aimed to quantify the growing non-communicable disease (NCD) burden in KSA between 2020 and 2030, and the impact this will have on the national health budget. Methods Ten priority NCDs were selected: ischemic heart disease, stroke, type 2 diabetes, chronic obstructive pulmonary disease, chronic kidney disease, dementia, depression, osteoarthritis, colorectal cancer, and breast cancer. Age- and sex-specific prevalence was projected for each priority NCD between 2020 and 2030. Treatment coverage rates were applied to the projected prevalence estimates to calculate the number of patients incurring treatment costs for each condition. For each priority NCD, the average cost-of-illness was estimated based on published literature. The impact of changes to our base-case model in terms of assumed disease prevalence, treatment coverage, and costs of care, coming into effect from 2023 onwards, were explored. Results The prevalence estimates for colorectal cancer and stroke were estimated to almost double between 2020 and 2030 (97% and 88% increase, respectively). The only priority NCD prevalence projected to increase by less than 60% between 2020 and 2030 was for depression (22% increase). It is estimated that the total cost of managing priority NCDs in KSA will increase from USD 19.8 billion in 2020 to USD 32.4 billion in 2030 (an increase of USD 12.6 billion or 63%). The largest USD value increases were projected for osteoarthritis (USD 4.3 billion), diabetes (USD 2.4 billion), and dementia (USD 1.9 billion). In scenario analyses, our 2030 projection for the total cost of managing priority NCDs varied between USD 29.2 billion - USD 35.7 billion. Conclusions Managing the growing NCD burden in KSA’s aging population will require substantial healthcare spending increases over the coming years.

Keywords: aging, non communicable disease, costs, Saudi Arabia

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3509 Analyzing the Performance of Machine Learning Models to Predict Alzheimer's Disease and its Stages Addressing Missing Value Problem

Authors: Carlos Theran, Yohn Parra Bautista, Victor Adankai, Richard Alo, Jimwi Liu, Clement G. Yedjou

Abstract:

Alzheimer's disease (AD) is a neurodegenerative disorder primarily characterized by deteriorating cognitive functions. AD has gained relevant attention in the last decade. An estimated 24 million people worldwide suffered from this disease by 2011. In 2016 an estimated 40 million were diagnosed with AD, and for 2050 is expected to reach 131 million people affected by AD. Therefore, detecting and confirming AD at its different stages is a priority for medical practices to provide adequate and accurate treatments. Recently, Machine Learning (ML) models have been used to study AD's stages handling missing values in multiclass, focusing on the delineation of Early Mild Cognitive Impairment (EMCI), Late Mild Cognitive Impairment (LMCI), and normal cognitive (CN). But, to our best knowledge, robust performance information of these models and the missing data analysis has not been presented in the literature. In this paper, we propose studying the performance of five different machine learning models for AD's stages multiclass prediction in terms of accuracy, precision, and F1-score. Also, the analysis of three imputation methods to handle the missing value problem is presented. A framework that integrates ML model for AD's stages multiclass prediction is proposed, performing an average accuracy of 84%.

Keywords: alzheimer's disease, missing value, machine learning, performance evaluation

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3508 Serum Levels of Plasminogen Activator Inhibitor-1 (PAI-1) Are Increased in Alzheimer’s Disease and MCI Patients and Correlate With Cognitive Deficits

Authors: Francesco Angelucci, Katerina Veverova, Alžbeta Katonová, Lydia Piendel, Martin Vyhnalek, Jakub Hort

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Alzheimer's disease (AD) is a central nervous system (CNS) disease characterized by loss of memory, cognitive functions and neurodegeneration. Plasmin is an enzyme degrading many plasma proteins. In the CNS, plasmin may reduce the accumulation of A, and have other actions relevant to AD pathophysiology. Brain plasmin synthesis is regulated by two enzymes: one activating, the tissue plasminogen activator (tPA), and the other inhibiting, the plasminogen activator inhibitor-1 (PAI-1). We investigated whether tPA and PAI-1 serum levels in AD and amnestic mild cognitive impairment (aMCI) patients are altered compared to cognitively healthy controls. Moreover, we examined the PAI-1/tPA ratio in these patient groups. 40 AD, 40 aMCI and 10 healthy controls were recruited. Venous blood was collected and PAI-1 and tPA serum concentrations were quantified by sandwich ELISAs. The results showed that PAI-1 levels increased in AD and aMCI patients. This increase negatively correlated with cognitive deficit measured by MMSE. Similarly, the ratio between tPA and PAI-1 gradually increases in aMCI and AD patients. This study demonstrates that AD and aMCI patients have altered PAI-1 serum levels and PAI-1/tPA ratio. Since these enzymes are CNS regulators of plasmin, PAI-1 serum levels could be a marker reflecting a cognitive decline in AD.

Keywords: Alzheimer disease, amnestic mild cognitive impairment, plasmin, tissue-type plasminogen activator

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3507 Strategies to Combat the Covid-19 Epidemic

Authors: Marziye Hadian, Alireza Jabbari

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Background: The World Health Organization has identified COVID-19 as a public health emergency and is urging governments to stop the virus transmission by adopting appropriate policies. In this regard, the countries have taken different approaches to cutting the chain or controlling the spread of the disease. Methods: The present study was a systematize review of publications relating to prevention strategies for covid-19 disease. The study was carried out based on the PRISMA guidelines and CASP for articles and AACODS for grey literature. Finding: The study findings showed that in order to confront the COVID-19 epidemic, in general, there are three approaches of "mitigation", "active control" and "suppression" and four strategies of "quarantine", "isolation", "social distance" as well as "lockdown" in both individual and social dimensions to deal with epidemics that the choice of each approach requires specific strategies and has different effects when it comes to controlling and inhibiting the disease. Conclusion: The only way to control the disease is to change your behavior and lifestyle. In addition to prevention strategies, use of masks, observance of personal hygiene principles such as regular hand washing and non-contact of contaminated hands with the face, as well as observance of public health principles such as control of sneezing and coughing, safe extermination of personal protective equipment, etc. have not been included in the category of prevention tools. However, it has a great impact on controlling the epidemic, especially the new coronavirus epidemic.

Keywords: novel corona virus, COVID-19, prevention tools, prevention strategies

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3506 Computational Agent-Based Approach for Addressing the Consequences of Releasing Gene Drive Mosquito to Control Malaria

Authors: Imran Hashmi, Sipkaduwa Arachchige Sashika Sureni Wickramasooriya

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Gene-drive technology has emerged as a promising tool for disease control by influencing the population dynamics of disease-carrying organisms. Various gene drive mechanisms, derived from global laboratory experiments, aim to strategically manage and prevent the spread of targeted diseases. One prominent strategy involves population replacement, wherein genetically modified mosquitoes are introduced to replace the existing local wild population. To enhance our understanding and aid in the design of effective release strategies, we employ a comprehensive mathematical model. The utilized approach employs agent-based modeling, enabling the consideration of individual mosquito attributes and flexibility in parameter manipulation. Through the integration of an agent-based model and a meta-population spatial approach, the dynamics of gene drive mosquito spreading in a released site are simulated. The model's outcomes offer valuable insights into future population dynamics, providing guidance for the development of informed release strategies. This research significantly contributes to the ongoing discourse on the responsible and effective implementation of gene drive technology for disease vector control.

Keywords: gene drive, agent-based modeling, disease-carrying organisms, malaria

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3505 Effects of Cranberry Juice Enriched with n-3 PUFA Consumption in Adjunct with Non-Surgical Periodontal Therapy on Glycemic Control, Antioxidant Status and Periodontal indices in Type 2 Diabetes Patients with Periodontitis

Authors: A. Zare Javid, H. Babaee, E. Ashrafzadeh, H. Yousefimanesh, M. Zakerkish, K. Ahmadi Angali, M. Ravanbakhsh

Abstract:

Introduction: Type 2 diabetes mellitus and periodontal disease hold a physiologically relationship. Periodontal disease, a common widespread chronic disease, is considered as an important complication in diabetes mellitus. The prevalence and severity of periodontal disease are increased among diabetic patients. A balanced nutrition may improve either diabetes or periodontal disease by controlling one of them. The aim of this study was to evaluate the effects of cranberry juice enriched with n-3 PUFA and their individual consumption on glycemic control and antioxidant status in diabetic patients with periodontal disease. Methods: In this randomized clinical trial 41 diabetic patients (35 – 65 y) with chronic adult periodontal disease were recruited from Endocrinology Clinic of Golestan Hospital in Ahvaz city, Iran. Subjects were randomly assigned to four groups as follow: one control group (n=12) and three intervention groups as receiving 1 g n-3 PUFA capsule (n=10), 400 ml cranberry juice (n=9), 400 ml cranberry juice enriched with 1g n-3 PUFA (n=10) for 8 weeks. Non-surgical periodontal therapy was provided for all patients during study. Fasting blood glucose, glycated hemoglobin, plasma and saliva TAOC and MDA, pocket depth and bleeding on probing were measured at baseline and post intervention. Results: There was a significant reduction in glycated hemoglobin observed in intervention groups of receiving n-3 PUFA and cranberry enriched with n-3 PUFA (11 %, P = 0.01 and 7 %, P = 0.01, respectively). The intervention group receiving n-3 PUFA had significantly lower glycated hemoglobin compared with control group. There was no significant difference found in FBS between and within groups. Furthermore, there was a significant increase in plasma TAOC only in cranberry enriched with n-3 PUFA group. Moreover, plasma MDA significantly decreased in intervention groups of receiving cranberry and cranberry enriched with n-3 PUFA. A significant increase was observed in TAOC of salvia in cranberry enriched with n-3 PUFA group compared to control group .The intervention group receiving cranberry enriched with n-3 PUFA had significantly lower MDA of salvia compared with control group. Pocket depth were significantly decreased in all groups, however, bleeding on probing didn’t significantly changed in patients post intervention. Conclusion: It is suggested that consumption of cranberry juice enriched with n-3 PUFA as a nutritional approach in adjunct with non-surgical periodontal therapy may help to improve glycosylated hemogolobin and TAOC in salvia and plasma in diabetic patients with periodontal disease.

Keywords: antioxidant, cranberry, oxidant status, periodontal disease, type 2 diabetes mellitus

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3504 Demographic Profile, Risk Factors and In-hospital Outcomes of Acute Coronary Syndrome (ACS) in Young Population, in Pakistan-Single Center Real World Experience

Authors: Asma Qudrat, Abid Ullah, Rafi Ullah, Ali Raza, Shah Zeb, Syed Ali Shan Ul-Haq, Shahkar Ahmed Shah, Attiya Hameed Khan, Saad Zaheer, Umama Qasim, Kiran Jamal, Zahoor khan

Abstract:

Objectives: Coronary artery disease (CAD) is the major public health issue associated with high mortality and morbidity rate worldwide. Young patients with ACS have unique characteristics with different demographic profiles and risk factors. The precise diagnosis and early risk stratification is important in guiding treatment and predicting the prognosis of young patients with ACS. To evaluate the associated demographics, risk factors, and outcomes profile of ACS in young age patients. Methods: The research follow a retrospective design, the single centre study of patients diagnosis with the first event of ACS in young age (>18 and <40) were included. Data collection included demographic profiles, risk factors, and in-hospital outcomes of young ACS patients. The patient’s data was retrieved through Electronic Medical Records (EMR) of Peshawar Institute of Cardiology (PIC), and all characteristic were assessed. Results: In this study, 77% were male, and 23% were female patients. The risk factors were assessed with CAD and shown significant results (P < 0.01). The most common presentation was STEMI, with (45%) most in ACS young patients. The angiographic pattern showed single vessel disease (SVD) in 49%, double vessel disease (DVD) in 17% and triple vessel disease (TVD) was found in 10%, and Left Artery Disease (LAD) (54%) was present to be the most common involved artery. Conclusion: It is concluded that the male sex was predominant in ACS young age patients. SVD was the common coronary angiographic finding. Risk factors showed significant results towards CAD and common presentations.

Keywords: coronary artery disease, Non-ST elevation myocardial infarction, ST elevation myocardial infarction, unstable angina, acute coronary syndrome

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3503 Self-Efficacy Psychoeducational Programme for Patients With End-Stage Renal Disease

Authors: H.C. Chen, S. W. C. Chan, K. Cheng, A. Vathsala, H. K. Sran, H. He

Abstract:

Background: End-stage renal disease (ESRD) is the last stage of chronic kidney disease. The numbers of patients with ESRD have increased worldwide due to the growing number of aging, diabetes and hypertension populations. Patients with ESRD suffer from physical illness and psychological distress due to complex treatment regimens, which often affect the patients’ social and psychological functioning. As a result, the patients may fail to perform daily self-care and self-management, and consequently experience worsening conditions. Aims: The study aims to examine the effectiveness of a self-efficacy psychoeducational programme on primary outcome (self-efficacy) and secondary outcomes (psychological wellbeing, treatment adherence, and quality of life) in patients with ESRD and haemodialysis in Singapore. Methodology: A randomised controlled, two-group pretest and repeated posttests design will be carried out. A total of 154 participants (n=154) will be recruited. The participants in the control group will receive a routine treatment. The participants in the intervention group will receive a self-efficacy psychoeducational programme in addition to the routine treatment. The programme is a two-session of educational intervention in a week. A booklet, two consecutive sessions of face-to-face individual education, and an abdominal breathing exercise are adopted in the programme. Outcome measurements include Dialysis Specific Self-efficacy Scale, Kidney Disease Quality of Life- 36 Hospital Anxiety and Depression Scale, Renal Adherence Attitudes Questionnaire and Renal Adherence Behaviour Questionnaire. The questionnaires will be used to measure at baseline, 1- and 3- and 6-month follow-up periods. Process evaluation will be conducted with a semi-structured face to face interview. Quantitative data will be analysed using SPSS21.0 software. Qualitative data will be analysed by content analysis. Significance of the study: This study will identify a clinically useful and potentially effective approach to help patients with end-stage renal disease and haemodialysis by enhancing their self-efficacy in self-care behaviour, and therefore improving their psychological wellbeing, treatment adherence and quality of life. This study will provide information to develop clinical guidelines to improve patients’ disease self-management and to enhance health-related outcomes. Hopefully it will help reducing disease burden.

Keywords: end-stage renal disease (ESRD), haemodialysis, psychoeducation, self-efficacy

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3502 Parkinson’s Disease Hand-Eye Coordination and Dexterity Evaluation System

Authors: Wann-Yun Shieh, Chin-Man Wang, Ya-Cheng Shieh

Abstract:

This study aims to develop an objective scoring system to evaluate hand-eye coordination and hand dexterity for Parkinson’s disease. This system contains three boards, and each of them is implemented with the sensors to sense a user’s finger operations. The operations include the peg test, the block test, and the blind block test. A user has to use the vision, hearing, and tactile abilities to finish these operations, and the board will record the results automatically. These results can help the physicians to evaluate a user’s reaction, coordination, dexterity function. The results will be collected to a cloud database for further analysis and statistics. A researcher can use this system to obtain systematic, graphic reports for an individual or a group of users. Particularly, a deep learning model is developed to learn the features of the data from different users. This model will help the physicians to assess the Parkinson’s disease symptoms by a more intellective algorithm.

Keywords: deep learning, hand-eye coordination, reaction, hand dexterity

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3501 Hyper Tuned RBF SVM: Approach for the Prediction of the Breast Cancer

Authors: Surita Maini, Sanjay Dhanka

Abstract:

Machine learning (ML) involves developing algorithms and statistical models that enable computers to learn and make predictions or decisions based on data without being explicitly programmed. Because of its unlimited abilities ML is gaining popularity in medical sectors; Medical Imaging, Electronic Health Records, Genomic Data Analysis, Wearable Devices, Disease Outbreak Prediction, Disease Diagnosis, etc. In the last few decades, many researchers have tried to diagnose Breast Cancer (BC) using ML, because early detection of any disease can save millions of lives. Working in this direction, the authors have proposed a hybrid ML technique RBF SVM, to predict the BC in earlier the stage. The proposed method is implemented on the Breast Cancer UCI ML dataset with 569 instances and 32 attributes. The authors recorded performance metrics of the proposed model i.e., Accuracy 98.24%, Sensitivity 98.67%, Specificity 97.43%, F1 Score 98.67%, Precision 98.67%, and run time 0.044769 seconds. The proposed method is validated by K-Fold cross-validation.

Keywords: breast cancer, support vector classifier, machine learning, hyper parameter tunning

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3500 Antihypertensive Activity of Alcoholic Extract of Citrus Paradise Juice in One Clip One Kidney Hypertension Model in Rats

Authors: Lokesh Bhatt, Jayesh Rathod

Abstract:

Hypertension is one of the most prevalent cardiovascular disorder. It is responsible for several other cardiovascular disorders. Although many drugs are available for the treatment of hypertension, still a large population has uncontrolled blood pressure. Thus there is an unmet need for new therapeutic approaches for the same. Fruit juice of Citrus paradise contains several flavonoids with vasodilatory activity. We hypothesized that alcoholic extract of Citrus paradise, which contains flavonoids, might attenuate hypertension. The objective of the present study was to evaluate the antihypertensive activity of alcoholic extract of Citrus paradise fruit juice in rats. Hypertension was induced using one clip one kidney model in rats. The renal artery was occluded for 4 h after removal of one kidney. Once stabilized, the ganglionic blockade was performed followed by removal of the arterial clip from the kidney. Removal of clip resulted in an increase in blood pressure which is due to release of renin from the kidney. Alcoholic extract of Citrus paradise fruit juice was then administered at 50 mg/kg and 100 mg/kg dose by intravenous injection. Blood pressure was monitored continuously. Alcoholic extract of Citrus paradise fruit juice reduced hypertension in dose-dependent manner. Antihypertensive activity was found to be associated with vasodilation. The results of the present study showed antihypertensive potential of alcoholic extract of Citrus paradise fruit juice.

Keywords: citrus paradise, alcoholic extract, one clip one kidney model, vasodilation

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3499 Insulin Receptor Substrate-1 (IRS1) and Transcription Factor 7-Like 2 (TCF7L2) Gene Polymorphisms Associated with Type 2 Diabetes Mellitus in Eritreans

Authors: Mengistu G. Woldu, Hani Y. Zaki, Areeg Faggad, Badreldin E. Abdalla

Abstract:

Background: Type 2 diabetes mellitus (T2DM) is a complex, degenerative, and multi-factorial disease, which is culpable for huge mortality and morbidity worldwide. Even though relatively significant numbers of studies are conducted on the genetics domain of this disease in the developed world, there is huge information gap in the sub-Saharan Africa region in general and in Eritrea in particular. Objective: The principal aim of this study was to investigate the association of common variants of the Insulin Receptor Substrate 1 (IRS1) and Transcription Factor 7-Like 2 (TCF7L2) genes with T2DM in the Eritrean population. Method: In this cross-sectional case control study 200 T2DM patients and 112 non-diabetes subjects were participated and genotyping of the IRS1 (rs13431179, rs16822615, 16822644rs, rs1801123) and TCF7L2 (rs7092484) tag SNPs were carries out using PCR-RFLP method of analysis. Haplotype analyses were carried out using Plink version 1.07, and Haploview 4.2 software. Linkage disequilibrium (LD), and Hardy-Weinberg equilibrium (HWE) analyses were performed using the Plink software. All descriptive statistical data analyses were carried out using SPSS (Version-20) software. Throughout the analysis p-value ≤0.05 was considered statistically significant. Result: Significant association was found between rs13431179 SNP of the IRS1 gene and T2DM under the recessive model of inheritance (OR=9.00, 95%CI=1.17-69.07, p=0.035), and marginally significant association found in the genotypic model (OR=7.50, 95%CI=0.94-60.06, p=0.058). The rs7092484 SNP of the TCF7L2 gene also showed markedly significant association with T2DM in the recessive (OR=3.61, 95%CI=1.70-7.67, p=0.001); and allelic (OR=1.80, 95%CI=1.23-2.62, p=0.002) models. Moreover, eight haplotypes of the IRS1 gene found to have significant association withT2DM (p=0.013 to 0.049). Assessments made on the interactions of genotypes of the rs13431179 and rs7092484 SNPs with various parameters demonstrated that high density lipoprotein (HDL), low density lipoprotein (LDL), waist circumference (WC), and systolic blood pressure (SBP) are the best T2DM onset predicting models. Furthermore, genotypes of the rs7092484 SNP showed significant association with various atherogenic indexes (Atherogenic index of plasma, LDL/HDL, and CHLO/HDL); and Eritreans carrying the GG or GA genotypes were predicted to be more susceptible to cardiovascular diseases onset. Conclusions: Results of this study suggest that IRS1 (rs13431179) and TCF7L2 (rs7092484) gene polymorphisms are associated with increased risk of T2DM in Eritreans.

Keywords: IRS1, SNP, TCF7L2, type 2 diabetes

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3498 Associations Between Psychological Distress and COVID-19 Disease Course: A Retrospective Cohort Study of 3084 Cases in Belgium

Authors: Gwendy Darras, Mattias Desmet

Abstract:

Previous research showed that psychological distress has a negative impact on the disease course of viral infections. For COVID-19, the same association was observed in small samples of specific segments of the population (e.g. health care workers). The present study presents a more refined analysis of this association, measuring a broader spectrum of psychological distress in a large sample (n=3084) of the general Flemish population. Several types of psychological distress (state, trait and health anxiety, depression, intra-, and interpersonal stress) are registered throughout three periods: one year before the contamination, one week before the contamination, and during the contamination. In doing so, validated scales such as DASS-21, IIP-32, and FCV-19S are used. Furthermore, the course of COVID-19 is registered in several ways: number of symptoms, number of days sick leave due to COVID-19, and number of days the symptoms have lasted. Also, different control variables such as vaccination status, medical and psychological history are taken into account. Statistical analysis shows that all types of psychological distress are positively correlated with the severity of the COVID-19 disease course. Anxiety during the contamination shows the strongest correlation, but psychological distress one year before the onset of COVID-19 was still significantly associated with the worsening of the disease course. As the assessment of the latter type of distress happened before the onset of the COVID-19 disease course, retrospective bias resulting in artificial associations between self-reported stress and COVID-19 severity is unlikely to have impacted the observations. In view of possible future pandemics, it is important to focus on general stress and anxiety reduction in the general population as soon as possible. It is also advisable to minimize the use of stress-inducing messages to encourage the population to adhere to the measures issued during a pandemic.

Keywords: anxiety, COVID-19, depression, psychoneuroimmunology, psychological distress, stress

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3497 Transcriptome Analysis for Insights into Disease Progression in Dengue Patients

Authors: Abhaydeep Pandey, Shweta Shukla, Saptamita Goswami, Bhaswati Bandyopadhyay, Vishnampettai Ramachandran, Sudhanshu Vrati, Arup Banerjee

Abstract:

Dengue virus infection is now considered as one of the most important mosquito-borne infection in human. The virus is known to promote vascular permeability, cerebral edema leading to Dengue hemorrhagic fever (DHF) or Dengue shock syndrome (DSS). Dengue infection has known to be endemic in India for over two centuries as a benign and self-limited disease. In the last couple of years, the disease symptoms have changed, manifesting severe secondary complication. So far, Delhi has experienced 12 outbreaks of dengue virus infection since 1997 with the last reported in 2014-15. Without specific antivirals, the case management of high-risk dengue patients entirely relies on supportive care, involving constant monitoring and timely fluid support to prevent hypovolemic shock. Nonetheless, the diverse clinical spectrum of dengue disease, as well as its initial similarity to other viral febrile illnesses, presents a challenge in the early identification of this high-risk group. WHO recommends the use of warning signs to identify high-risk patients, but warning signs generally appear during, or just one day before the development of severe illness, thus, providing only a narrow window for clinical intervention. The ability to predict which patient may develop DHF and DSS may improve the triage and treatment. With the recent discovery of high throughput RNA sequencing allows us to understand the disease progression at the genomic level. Here, we will collate the results of RNA-Sequencing data obtained recently from PBMC of different categories of dengue patients from India and will discuss the possible role of deregulated genes and long non-coding RNAs NEAT1 for development of disease progression.

Keywords: long non-coding RNA (lncRNA), dengue, peripheral blood mononuclear cell (PBMC), nuclear enriched abundant transcript 1 (NEAT1), dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS)

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3496 Effects of Blood Pressure According to Age on End-Stage Renal Disease Development in Diabetes Mellitus Patients: A Nationwide Population-Based Cohort Study

Authors: Eun Hui Bae, Sang Yeob Lim, Bongseong Kim, Tae Ryom Oh, Su Hyun Song, Sang Heon Suh, Hong Sang Choi, Eun Mi Yang, Chang Seong Kim, Seong Kwon Ma, Kyung-Do Han, Soo Wan Kim

Abstract:

Background: Recent hypertension guidelines have recommended lower blood pressure (BP) targets in high-risk patients. However, there are no specific guidelines based on age or systolic and diastolic blood pressure (SBP and DBP, respectively). We aimed to assess the effects of age-related BP on the development of end-stage renal disease (ESRD) in patients with diabetes. Methods: A total of 2,563,870 patients with DM aged >20 years were selected from the Korean National Health Screening Program from 2009 to 2012 and followed up until the end of 2019. Participants were categorized into age and BP groups, and the hazard ratios (HRs) for ESRD were calculated. Results: During a median follow-up of 7.15 years, the incidence rates of ESRD increased with increasing SBP and DBP. The HR for ESRD was the highest in patients younger than 40 years of age with DBP ≥ 100 mmHg. The effect of SBP and DBP on ESRD development was attenuated with age (interaction p-value was <0.0001 for age and SBP and 0.0022 for age and DBP). The subgroup analysis for sex, anti-hypertension medication, and history of chronic kidney disease (CKD) showed higher HRs for ESRD among males younger than 40 years, not taking anti-hypertension medications and CKD compared to those among females older than 40 years, anti-hypertension medication and non-CKD groups. Conclusions: Higher SBP and DBP increase the risk of developing ESRD in patients with diabetes, and in particular, younger individuals face greater risk. Therefore, intensive BP management is warranted in younger patients to prevent ESRD.

Keywords: hypertension, young adult, end-stage renal disease, diabetes mellitus, chronic kidney disease, blood pressure

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3495 Expression of ULK-1 mRNA in Human Peripheral Blood Mononuclear Cells from Patients with Alzheimer's Disease

Authors: Ali Bayram, Remzi Yiğiter

Abstract:

Objective: Alzheimer's disease (AD), the most common cause of dementia, is a progressive neurodegenerative disease. At present, diagnosis of AD is rather late in the disease. Therefore, we attempted to find peripheral biomarkers for the early diagnosis of AD. Herein, we conducted a study to investigate the unc-51 like autophagy activating kinase-1 (ULK1) mRNA expression levels in human peripheral blood mononuclear cells from patients with Alzheimer's disease. Method: To determine whether ULK1 gene expression are altered in AD patients, we measured their gene expression in human peripheral blood cell in 50 patients with AD and 50 age and gender matched healthy controls by quantitative real-time PCR technique. Results: We found that both ULK1 gene expression in peripheral blood cell were significantly decreased in patients with AD as compared with controls (p <0.05). Lower levels of ULK1 gene expression were significantly associated with the increased risk for AD. Conclusions: Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2, and PRKAG1, leading to negatively regulate AMPK activity. May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences. Plays a role early in neuronal differentiation and is required for granule cell axon formation. Alzheimer is the most common neurodegenerative disease. Our results provide useful information that the ULK1 gene expression is decreased in the neurodegeneration and AD patients with, indicating their possible systemic involvement in AD.

Keywords: Alzheimer’s sisease, ULK1, mRNA expression, RT-PCR

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3494 Muscle Relaxant Dantrolene Repurposed to Treat Alzheimer's Disease

Authors: Huafeng Wei

Abstract:

Failures of developing new drugs primarily based on the amyloid pathology hypothesis after decades of efforts internationally lead to changes of focus targeting alternative pathways of pathology in Alzheimer’s disease (AD). Disruption of intracellular Ca2+ homeostasis, especially the pathological and excessive Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) Ca2+ channels, has been considered an upstream pathology resulting in major AD pathologies, such as amyloid and Tau pathology, mitochondria damage and inflammation, etc. Therefore, dantrolene, an inhibitor of RyRs that reduces the pathological Ca2+ release from ER and a clinically available drug for the treatment of malignant hyperthermia and muscle spasm, is expected to ameliorate AD multiple pathologies synapse and cognitive dysfunction. Our own studies indicated that dantrolene ameliorated impairment of neurogenesis and synaptogenesis in neurons developed from induced pluripotent stem cells (iPSCs) originated from skin fibroblasts of either familiar (FAD) or sporadic (SAD) AD by restoring intracellular Ca2+ homeostasis. Intranasal administration of dantrolene significantly increased its passage across the blood-brain barrier (BBB) and, therefore its brain concentrations and durations. This can render dantrolene a more effective therapeutic drug with fewer side effects for chronic AD treatment. This review summarizes the potential therapeutic and side effects of dantrolene and repurposes intranasal dantrolene as a disease-modifying drug for future AD treatment.

Keywords: Alzheimer's disease, calcium, drug development, dementia, neurodegeneration, neurogenesis

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