Search results for: disease progression

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

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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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Authors: Liudmila Garzanova, Lidia Ananyeva, Olga Koneva, Olga Ovsyannikova, Oxana Desinova, Mayya Starovoytova, Rushana Shayahmetova, Anna Khelkovskaya-Sergeeva

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Objectives. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are associated with severe course, increased morbidity and mortality in systemic sclerosis (SSc). The aim of our study was to assess changes in CRP and ESR in SSc patients during long-term RTX therapy. Methods. This study included 113 patients with SSc. Mean age was 48.1±13 years, female-85%. The mean disease duration was 6±5 years. The diffuse cutaneous subset of the disease had 55% of patients. All pts had interstitial lung disease (ILD). All patients received prednisolone at a mean dose of 11.6±4.8 mg/day, and 53 of them - were immunosuppressants at inclusion. Patients received RTX due to the ineffectiveness of previous therapy for ILD. The parameters were evaluated over the periods: at baseline (point 0), 13±2.3 month (point 1, n=113), 42±14 month (point 2, n=80) and 79±6.5 month (point 3, n=25) after initiation of RTX therapy. Cumulative mean dose of RTX at point 1 = 1.7±0.6g, at point 2 = 3±1.5g, and at point 3 = 3.8±2.4g. The results are presented in the form of mean values, delta(Δ)-difference between the baseline parameter and follow-up point. Results. There was an improvement in studied parameters on RTX therapy. There was a significant decrease of ESR, CRP and activity index (EScSG-AI) at all observation points (p=0.001). In point 1: ΔCRP was 6.7 mg/l, ΔESR = 7.4 mm/h, ΔActivity index (EScSG-AI) = 1.7. In point 2: ΔCRP was 8.7 mg/l, ΔESR = 7.5 mm/h, ΔActivity index (EScSG-AI) = 1.9. In point 3: ΔCRP was 16.1 mg/l, ΔESR = 11 mm/h, ΔActivity index (EScSG-AI) = 2.1. Conclusion. There was a significant decrease in CRP and ESR during long-term RTX therapy, which correlated with a decrease in the disease activity index. RTX is an effective treatment option for SSc with an elevation of acute-phase reactants.

Keywords: C-reactive protein, interstitial lung disease, systemic sclerosis, rituximab

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Authors: Abhigyan Hedau, Priya Shelke, Riddhi Mirajkar, Shreyash Chaple, Mrunali Gadekar, Himanshu Akula

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The heart is the coordinating centre of the major endocrine glandular structure of the body, which produces hormones that profoundly affect the operations of the body, and diagnosing cardiovascular disease is a difficult but critical task. By extracting knowledge and information about the disease from patient data, data mining is a more practical technique to help doctors detect disorders. We use a variety of machine learning methods here, including logistic regression and support vector classifiers (SVC), K-nearest neighbours Classifiers (KNN), Decision Tree Classifiers, Random Forest classifiers and Gradient Boosting classifiers. These algorithms are applied to patient data containing 13 different factors to build a system that predicts heart disease in less time with more accuracy.

Keywords: logistic regression, support vector classifier, k-nearest neighbour, decision tree, random forest and gradient boosting

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Authors: Hsiang-Ru Lin

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Cholesterol plays an essential role in the regulation of the progression of numerous important diseases including atherosclerosis and Alzheimer disease so the generation of suitable cholesterol-lowering reagents is urgent to develop. Liver X receptor (LXR) is a ligand-activated transcription factor whose natural ligands are cholesterols, oxysterols and glucose. Once being activated, LXR can transactivate the transcription action of various genes including CYP7A1, ABCA1, and SREBP1c, involved in the lipid metabolism, glucose metabolism and inflammatory pathway. Essentially, the upregulation of ABCA1 facilitates cholesterol efflux from the cells and attenuates the production of beta-amyloid (ABeta) 42 in brain so LXR is a promising target to develop the cholesterol-lowering reagents and preventative treatment of Alzheimer disease. Engelhardia roxburghiana is a deciduous tree growing in India, China, and Taiwan. However, its chemical composition is only reported to exhibit antitubercular and anti-inflammatory effects. In this study, four compounds, engelheptanoxides A, C, engelhardiol A, and B isolated from the root of Engelhardia roxburghiana were evaluated for their agonistic activity against LXR by the transient transfection reporter assays in the HepG2 cells. Furthermore, their interactive modes with LXR ligand binding pocket were generated by molecular modeling programs. By using the cell-based biological assays, engelheptanoxides A, C, engelhardiol A, and B showing no cytotoxic effect against the proliferation of HepG2 cells, exerted obvious LXR agonistic effects with similar activity as T0901317, a novel synthetic LXR agonist. Further modeling studies including docking and SAR (structure-activity relationship) showed that these compounds can locate in LXR ligand binding pocket in the similar manner as T0901317. Thus, LXR is one of nuclear receptors targeted by pharmaceutical industry for developing treatments of Alzheimer and atherosclerosis diseases. Importantly, the cell-based assays, together with molecular modeling studies suggesting a plausible binding mode, demonstrate that engelheptanoxides A, C, engelhardiol A, and B function as LXR agonists. This is the first report to demonstrate that the extract of Engelhardia roxburghiana contains LXR agonists. As such, these active components of Engelhardia roxburghiana or subsequent analogs may show important therapeutic effects through selective modulation of the LXR pathway.

Keywords: Liver X receptor (LXR), Engelhardia roxburghiana, CYP7A1, ABCA1, SREBP1c, HepG2 cells

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

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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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Authors: Marjan Mahdavi-Roshan, Arsalan Salari, Mahboobeh Gholipour, Moona Naghshbandi

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Background and objectives: Before any nutritional intervention, it is necessary to have the prospect of eating habits of people with cardiovascular risk factors. In this study, we assessed the adherence of healthy diet based on Mediterranean dietary pattern and related factors in adults in the north of Iran. Methods: This study was conducted on 550 men and women with cardiovascular risk factors that referred to Heshmat hospital in Rasht, northern Iran. Information was collected by interview and reading medical history and measuring anthropometric indexes. The Mediterranean Diet Adherence Screener was used for assessing dietary adherence, this screener was modified according to religious beliefs and culture of Iran. Results: The mean age of participants was 58±0.38 years. The mean of body mass index was 27±0.01 kg/m², and the mean of waist circumference was 98±0.2 cm. The mean of dietary adherence was 5.76±0.07. 45% of participants had low adherence, and just 4% had suitable adherence. The mean of dietary adherence in men was significantly higher than women (p=0. 07). Participants in rural area and high educational participants insignificantly had an unsuitable dietary Adherence. There was no significant association between some cardiovascular disease risk factors and dietary adherence. Conclusion: Education to different group about dietary intake correction and using a Mediterranean dietary pattern that is similar to dietary intake in the north of Iran, for controlling cardiovascular disease is necessary.

Keywords: dietary adherence, Mediterranean dietary pattern, cardiovascular disease, north of Iran

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

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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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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

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

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

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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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Authors: Surita Maini, Sanjay Dhanka

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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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Authors: Gwendy Darras, Mattias Desmet

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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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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

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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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Authors: Ali Bayram, Remzi Yiğiter

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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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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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Authors: Francesca La Rosa , Marina Saresella, Mario Clerici, Michael Heneka

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Neuroinflammation plays a key role in the modulation of the pathogenesis of neurodegenerative disorder such as Alzheimer's Disease (AD). Microglia, the main immune effector of the brain, are able to migrate to sites of Amyloid-beta (Aβ) deposition to eliminate Aβ phagocytosis upon activation by multiple receptors: Toll like receptors and scavenger receptors. The issue of whether microglia are able to eliminate pathological lesions such as neurofibrillary tangles or senile plaques from AD brain still remains the matter of controversy. Recent data suggest that the Nod Like Receptor 3 (NLRP3), multiprotein inflammasome complexes, plays a role in AD, as its activation in the microglia by Aβ triggers. IL-1β is produced as a biologically inactive pro-form and requires caspase-1 for activation and secretion. Caspase-1 activity is controlled by inflammasomes. We investigate about the importance of inflammasomes complex in the Aβ phagocytosis and its degradation. The preliminary results of phagocytosis assay and immunofluorescent experiment on primary Microglia cells to lipopolysaccharide (LPS) an Aβ exposure show that a previous treatment with LPS reduce Aβ phagocytosis. Different results were obtained in Primary Microglia wild type, NLRP3 and ASC Knockout suggesting a real inflammasomes involvement in Alzheimer's pathology. Inflammasomes inactivation reduces the production of inflammatory cytokines prolonging the protective activity of microglia and Aβ clearance, featuring a typical microglia phenotype of the early stage of AD disease.

Keywords: Alzheimer disease, innate immunity, neuroinflammation, NLRP3

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Authors: Kritin K. Verma, Brian L. Ransdell

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White patches are a symptom of vitiligo, a chronic autoimmune dermatological condition that causes a loss of pigmentation in the skin. Vitiligo can cause issues of self-esteem and quality of life while also progressing the development of other autoimmune diseases. Current treatments in allopathy and homeopathy exist; some treatments have been found to be toxic, whereas others have been helpful. Allopathy has seemed to offer several treatment plans, such as phototherapy, skin lightening preparations, immunosuppressive drugs, combined modality therapy, and steroid medications to improve vitiligo. This presentation will review the FDA-approved topical cream, Opzelura, a JAK inhibitor, and its effects on limiting vitiligo progression. Meanwhile, other non-conventional methods, such as Arsenic Sulphuratum Flavum used in homeopathy, will be debunked based on current literature. Most treatments still serve to arrest progression and induce skin repigmentation. Treatment plans may differ between patients due to depigmentation location on the skin. Since there is no gold standard plan for treating patients with vitiligo, the oral presentation will review all topical and systemic pharmacological therapies that fight the depigmentation of the skin and categorize their validity from a systematic review of the literature. Since treatment plans are limited in nature, all treatment methods will be mentioned and an attempt will be made to make a golden standard treatment process for these patients.

Keywords: vitiligo, phototherapy, immunosuppressive drugs, skin lightening preparations, combined modality therapy, arsenic sulphuratum flavum, homeopathy, allopathy, golden standard, Opzelura

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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 well-being, 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 and it will help reducing disease burden.

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

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Authors: Comsun Thongchai, Vorapoj Promasatayaprot

Abstract:

Background: Child development center is a day care center that gathers large numbers of children in the same areas. As a result, it provides high opportunity for infection, especially gastrointestinal and respiratory infections. Ubon Ratchathani has been a province with an increasing number of cases of Hand foot and mouth disease each year reported between 2014 and 2016. Accorded to a recent investigation reported, HFMD occurred in the Child Development Center and kindergartens, this was a place where HFMD spreads. This research was aimed to investigate the knowledge, attitude and behavior about hand foot and mouth disease preventing of child caregivers in child development centers, Ubon Ratchathani Province. Method: Descriptive study was conducted between April and July, 2017. The study instruments used questionnaires and in-depth interviews on their practices of prevention and environment management of HFMD. The samples of survey questionnaires were caregivers who are working in 160 child development centers of the 160 parishes in Ubon Ratchathani province. The data was analyzed by percentages, means and standard deviations and Pearson Product Moment Correlation Coefficient. Result: The results showed that the majority were female (96.3%), average age 41 years (68.3%), marital status were couples (85.7%) and studied in undergraduate (75.2%). with a period of performance as teachers in child development centers range from 10 to 14 years were percentage 58.7 and 71.8 percent of them had been trained by health worker about the control HFMD. The knowledge for preventive in hand foot mouth disease on child caregivers was at high level. The mean score was 2.76 (S.D. = 0.114). The attitude of child caregivers was at a moderate level. Its mean score was 2.28 (S.D. = 0.247). On the other hand, the level of environmental management to prevent HFMD was low. The mean score was 1.34 (S.D. = 0.215). The factor of personal characteristics as gender, age, educational level, duration at work, knowledge and attitude of preventive HFMD was associated with Preventive of Behaviors to a statistically significant level (p<0.05 respectively). Conclusion: These results should be concerned to develop knowledge and improving practice for preventive hand foot mouth disease of child caregivers in child development centers by training. Preparation of media education, Surveillance of hand foot mouth disease and health behaviors promotion with community participation need to be supported continuously.

Keywords: preventive behavior, child development center, hand foot mouth disease, Thailand

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Authors: Angelis P. Barlampas

Abstract:

Objective: The confusion of terms is a common practice in many situations of the everyday life. But, in some circumstances, such as in medicine, the precise meaning of a word curries a critical role for the health of the patient. Fahr disease and Fahr syndrome are often falsely used interchangeably, but they are two different conditions with different physical histories of different etiology and different medical management. A case of the seldom Fahr disease is presented, and a comparison with the more common Fahr syndrome follows. Materials and method: A 72 years old patient came to the emergency department, complaining of some kind of non specific medal disturbances, like anxiety, difficulty of concentrating, and tremor. The problems had a long course, but he had the impression of getting worse lately, so he decided to check them. Past history and laboratory tests were unremarkable. Then, a computed tomography examination was ordered. Results: The CT exam showed bilateral, hyperattenuating areas of heavy, dense calcium type deposits in basal ganglia, striatum, pallidum, thalami, the dentate nucleus, and the cerebral white matter of frontal, parietal and iniac lobes, as well as small areas of the pons. Taking into account the absence of any known preexisting illness and the fact that the emergency laboratory tests were without findings, a hypothesis of the rare Fahr disease was supposed. The suspicion was confirmed with further, more specific tests, which showed the lack of any other conditions which could probably share the same radiological image. Differentiating between Fahr disease and Fahr syndrome. Fahr disease: Primarily autosomal dominant Symmetrical and bilateral intracranial calcifications The patient is healthy until the middle age Absence of biochemical abnormalities. Family history consistent with autosomal dominant Fahr syndrome :Earlier between 30 to 40 years old. Symmetrical and bilateral intracranial calcifications Endocrinopathies: Idiopathic hypoparathyroidism, secondary hypoparathyroidism, hyperparathyroidism, pseudohypoparathyroidism ,pseudopseudohypoparathyroidism, e.t.c The disease appears at any age There are abnormal laboratory or imaging findings. Conclusion: Fahr disease and Fahr syndrome are not the same illness, although this is not well known to the inexperienced doctors. As clinical radiologists, we have to inform our colleagues that a radiological image, along with the patient's history, probably implies a rare condition and not something more usual and prompt the investigation to the right route. In our case, a genetic test could be done earlier and reveal the problem, and thus avoiding unnecessary and specific tests which cost in time and are uncomfortable to the patient.

Keywords: fahr disease, fahr syndrome, CT, brain calcifications

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Authors: Lai Yi-Hsiu

Abstract:

The present paper aims to examine the language processing of Chinese-speaking seniors with Alzheimer’s disease (AD) from the perspective of temporal cues. Twenty healthy adults, 17 healthy seniors, and 13 seniors with AD in Taiwan participated in this study to tell stories based on two sets of pictures. Nine temporal cues were fetched and analyzed. Oral productions in Mandarin Chinese were compared and discussed to examine to what extent and in what way these three groups of participants performed with significant differences. Results indicated that the age effects were significant in filled pauses. The dementia effects were significant in mean duration of pauses, empty pauses, filled pauses, lexical pauses, normalized mean duration of filled pauses and lexical pauses. The findings reported in the current paper help characterize the nature of language processing in seniors with or without AD, and contribute to the interactions between the AD neural mechanism and their temporal parameters.

Keywords: language processing, Alzheimer’s disease, Mandarin Chinese, temporal cues

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Authors: Kebret Kebede, Anthony Scinta

Abstract:

Obesity is the most prevalent global problem that continues to rise at alarming rates both in the industrialized and developing countries. Adipose tissue is an endocrine tissue that secretes numerous chemical signals, hormones, lipids, cytokines and coagulation factors as well as prompting insulin resistance which is a primary contributor to Type II Diabetes- one of its most common adverse effects on health. Other hormones whose levels are linked to obesity and nutritional state are leptin, IGF-1, and adiponectin. Several studies indicate that obesity is the leading cause of high levels of cholesterol that leads to fatty liver disease, gallstones, hypertension, increased risk for cancer and degenerative joint disease that primarily affects the weight bearing joints of the lower extremities. The activation of inflammatory pathways promotes synovial pathology that results in accelerated degeneration of the joints. The study examines the prevalence of obesity in the US female population in comparison to that of the developing world and its emergence as a significant and potentially modifiable risk factor in degenerative disease of the hip and knee joints that has resulted in staggering healthcare cost. Studies have shown that as the prevalence of obesity rises, we continue to see a rise in degenerative joint disease. The percentage of arthritis cases linked directly to obesity has risen from 3 percent in 1971 to 18 percent in 2002. A person with obesity is around 60 percent more likely to develop arthritis than someone of normal body weight. In women, obesity is associated with increased mortality from breast, cervical, endometrial and ovarian cancer that may accompany debilitating joint diseases and restricted mobility.

Keywords: obesity, endocrine, degenerative, mortality, joint diseases, cancer, debilitating, mobility

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Authors: Wissem Abdaoui, Nizar M. Mhaidat, Ilhem Mokhtari, Adel Gouri

Abstract:

Colorectal cancer (CRC) is one of the most common tumors all over the world. Obesity, considered a risk factor of CRC, is characterized by a high level of secreted cytokines from adipose tissue. Among these inflammatory molecules, leptin is considered the key mediator for CRC cancer development and progression by activation of mitogenic and anti apoptotic signaling pathways. Gene expression can be significantly modulated by alterations in DNA methylation patterns. The aim of this study is to investigate the impact of leptin gene methylation on CRC prognosis and sensitivity to chemotherapy. The study involved 70 CRC tissue samples collected from King Abdullah University Hospital (KAUH) from which only 53 was analyzed because of bisulfate fragmentation and low yield of DNA extracted from FFPE tissues. A total of 22 blood samples were collected from healthy volunteers and enrolled as a control group. Leptin promoter methylation was analyzed by methylation specific PCR after bisulfate conversion. Results revealed that the incidence of leptin gene methylation was significantly higher in CRC patients in comparison to that of controls (P < 0.05). The correlation between patient’s demographics and leptin gene methylation was not significant (P < 0.05). However, a significant correlation between leptin gene methylation status and early cancer stages (I, II and III) was found in male but not in female (p < 0.05). Moreover, a significant correlation was found between leptin promoter methylation and early tumor localization T1-2 (p < 0.05). The correlation between epigenetic regulation of leptin and chemosensitivity was not significant. Taken together, these results suggest the possibility to use leptin gene methylation as a biomarker for the evaluation of CRC prognosis and metastasis.

Keywords: colorectal cancer, obesity, leptin, DNA methylation, disease prognosis, bisulfate conversion, chemoresistance

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Authors: Somaiya Mateen, Shagufta Moin, Mohammad Owais, Abdul Khan, Atif Zafar

Abstract:

In rheumatoid arthritis (RA), impaired oxidative metabolism and imbalance between pro-and anti-inflammatory cytokines are responsible for causing inflammation and the degradation of cartilage and bone. The present study was done to evaluate the level and hence the role of reactive oxygen species (ROS) and inflammatory cytokines in the pathogenesis of RA. The present study was performed in the blood of 80 RA patients and 55 age and sex-matched healthy controls. The level of ROS (in 5% hematocrit) and the plasma level of pro-inflammatory cytokines [TNF-α, interleukin-6 (IL-6), IL-22] and anti-inflammatory cytokines (IL-4 and IL-5) were monitored in healthy subjects and RA patients. For evaluating the role of rheumatoid factor (RF) in the pathogenesis of RA, patients were sub-divided on the basis of presence or absence of RF. Reactive species and inflammatory cytokines were correlated with disease activity measure-Disease Activity Score for 28 joints (DAS28). The level of ROS, TNF-α, IL-6 and IL-22 were found to be significantly higher in RA patients as compared to the healthy controls, with the increase being more significant in patients positive for rheumatoid factor and those having high disease severity. On the other hand, a significant decrease in the level of IL-4 and IL-10 were observed in RA patients compared with healthy controls, with the decrease being more prominent in severe cases of RA. Higher ROS (indicative of impaired anti-oxidant defence system) and pro-inflammatory cytokines level in RA patients may lead to the damage of biomolecules which in turn contributes to tissue damage and hence to the development of more severe RA. The imbalance between pro-and anti-inflammatory cytokines may lead to the development of multi-system immune complications. ROS and inflammatory cytokines may also serve as a potential biomarker for assessing the disease severity.

Keywords: rheumatoid arthritis, reactive oxygen species, pro-inflammatory cytokines, anti-inflammatory cytokines

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