Search results for: disease specific genes

Authors: Sulemana Saibu, Moses Ikpeme

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Background: The severity of the COVID-19 pandemic, brought on by the SARS-CoV-2 coronavirus, has been unprecedented since the 1918 influenza pandemic. SARS-CoV-2 cases of CNS and peripheral nervous system disease, including neurodegenerative disorders and chronic immune-mediated diseases, may be anticipated based on knowledge of past coronaviruses, particularly those that caused the severe acute respiratory syndrome and Middle East respiratory syndrome outbreaks. Although respiratory symptoms are the most common clinical presentation, neurological symptoms are becoming increasingly recognized, raising concerns about their potential role in causing Parkinson's disease, Multiple sclerosis, and Narcolepsy. This systematic review aims to summarize the current evidence by exploring the association between COVID-19 infection and how it may overlap with etiological mechanisms resulting in Narcolepsy, Parkinson's disease, and Multiple sclerosis. Methods: A systematic search was conducted using electronic databases ((PubMed/MedLine, Embase, PsycINFO, ScieLO, Web of Science, ProQuest (Biotechnology, Virology, and AIDS), Scopus, and CINAHL)) to identify studies published between January 2020 and December 2022 that investigated the association between COVID-19 and Parkinson's disease, multiple sclerosis, and Narcolepsy. Per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the review was performed and reported. Study quality was assessed using the Critical Appraisal Skills Programme Checklist and the Joanna Briggs Institute Critical appraisal tools. Results: A total of 21 studies out of 1025 met the inclusion criteria, including 8 studies reporting Parkinson's disease, 11 on multiple sclerosis, and 2 on Narcolepsy. In COVID-19 individuals compared to the general population, Narcolepsy, Parkinson's disease, and multiple sclerosis were shown to have a higher incidence. The findings imply that COVID-19 may worsen the signs or induce multiple sclerosis and Parkinson's disease and may raise the risk of developing Narcolepsy. Further research is required to confirm these connections because the available data is insufficient. Conclusion: According to the existing data, COVID-19 may raise the risk of Narcolepsy and have a causative relationship with Parkinson's disease, multiple sclerosis, and other diseases. More study is required to confirm these correlations and pinpoint probable mechanisms behind these interactions. Clinicians should be aware of how COVID-19 may affect various neurological illnesses and should treat patients who are affected accordingly.

Keywords: COVID-19, parkinson’s disease, multiple sclerosis, narcolepsy, neurological disorders, sars-cov-2, neurodegenerative disorders, chronic immune-mediated diseases

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Authors: Avik Banerjee, Kavita Saggar

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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)

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Authors: Emad Heydarnia, Aref Sepasi, Nika Asefi, Sara Khakshournia, Javad Mohammadnejad

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Background: Despite breakthrough therapeutics in breast cancer, it is one of the main causes of mortality among women worldwide. Thus, drug therapies for treating breast cancer have recently been developed by scientists. Metformin and Sorafenib are well-known therapeutic in breast cancer. In the present study, we combined Sorafenib and PCL-sorafenib with metformin to improve drug absorption and promote therapeutic efficiency. Methods: The MCF-7 cells were treated with Metformin, Sorafenib, or PCL-sorafenib. The growth inhibitory effect of these drugs and cell viability were assessed using MTT and flow cytometry assays, respectively. The expression of targeted genes involved in cell proliferation, signaling, and the cell cycle was measured by Real-time PCR. Results: The results showed that MCF-7 cells treated with Metformin/Sorafenib and PCL-sorafenib/Metformin co-treatment contributed to 50% viability compared to untreated group. Moreover, PI and Annexin V staining tests showed that the cells viability for Metformin/Sorafenib and PCL-sorafenib/Metformin was 38% and 17%, respectively. Furthermore, Sorafenib/Metformin and PCL-sorafenib/Metformin leads to p53 gene expression increase by which they can increase ROS, thereby decreasing GPX4 gene expression. In addition, they affected the expression of BCL2, and BAX genes and altered the cell cycle. Conclusion: Together, the combination of PCL-sorafenib/Metformin and Sorafenib/Metformin increased Sorafenib absorption at lower doses and also leads to apoptosis and oxidative stress increases in MCF-7 cells.

Keywords: breast cancer, metformin, nanotechnology, sorafenib

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Authors: S. Ibrahim, D. Salilew-Wondim, M. Hoelker, C. Looft, E. Tholen, C. Grosse-Brinkhaus, K. Schellander, C. Neuhoff, D. Tesfaye

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Bovine endometrial cells appear to have a key role in innate immune defense of the female genital tract. A better understanding of molecular changes in microRNAs (miRNAs) and their target genes expression may identify reliable prognostic indicators for cows that will resolve inflammation and resume cyclicity. In the current study, we hypothesized that let-7 miRNAs family has a primary role in the innate immune defence of the endometrium tissue against bacterial infection, which is partly achieved via regulating mRNA stability of pro-inflammatory cytokines at the post-transcriptional level. Therefore, we conducted two experiments. In the first experiment, primary bovine endometrial cells were challenged with clinical (3.0 μg/ml) and sub-clinical (0.5 μg/ml) doses of lipopolysaccharide (LPS) for 24h. In the 2nd experiment, we have investigated the potential role of let-7 miRNAs (let-7a and let-7f) using gain and loss of function approaches. Additionally, tumor necrosis factor alpha (TNFα), transforming growth factor beta 1 induced transcript 1 (TGFB1I1) and serum deprivation response (SDPR) genes were validated using reporter assay. Here we addressed for the first time that let-7 miRNAs have a precise role in bovine endometrium, where LPS dysregulated let-7 miRNAs family expression was associated with an increased pro-inflammatory cytokine level by directly/indirectly targeting the TNFα, interleukin 6 (IL6), nuclear factor kappa-light-chain enhancer of activated B cells (NFκB), TGFβ1I1 and SDPR genes. To our knowledge, this is the first study showing that TNFα, TGFβ1I1 and SDPR were identified and validated as novel let-7 miRNAs targets and could have a distinct role in inflammatory immune response of LPS challenged bovine endometrial cells. Our data represent a new finding by which uterine homeostasis is maintained through functional regulation of let-7a by down-regulation of pro-inflammatory cytokines expression (TNFα and IL6) at the mRNA and protein levels. These findings suggest that LPS serves as a negative regulator of let-7 miRNAs expression and provides a mechanism for the persistent pro-inflammatory phenotype, which is a hallmark of bovine subclinical endometritis.

Keywords: bovine endometrial cells, let-7, lipopolysaccharide, pro-inflammatory cytokines

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Authors: Naso Isaiah Thanavisuth

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Medical cannabis can be used for treatment including pain, multiple sclerosis, Parkinson's disease, and cancer. However, medical cannabis leads to adverse effects (AEs), which is delta-9-tetrahydrocannabinol (THC). In previous studies, the major of THC metabolism enzymes are CYP2C9. Especially, the variation of CYP2C9 gene consist of CYP2C9*2 on exon 3 and CYP2C9*3 on exon 7 to decrease enzyme activity. Notwithstanding, there is no data describing whether the variant of CYP2C9 genes are apharmacogenetics marker for the prediction of THC-induced AEs in Thai patients. We want to investigate the association between CYP2C9 gene and THC-induced AEs in Thai patients. We enrolled 39 Thai patients with medical cannabis treatment who were classified by clinical data. The CYP2C9*2 and *3 genotyping were conducted using the TaqMan real time PCR assay. All Thai patients who received the medical cannabis consist of twenty-four (61.54%) patients were female, and fifteen (38.46%) were male, with age range 27- 87 years. Moreover, the most AEs in Thai patients who were treated with medical cannabis between cases and controls were tachycardia, arrhythmia, dry mouth, and nausea. Particularly, thirteen (72.22%) medical cannabis-induced AEs were female and age range 33 – 69 years. In this study, none of the medical cannabis groups carried CYP2C9*2 variants in Thai patients. The CYP2C9*3 variants (*1/*3, intermediate metabolizer, IM) and (*3/*3, poor metabolizer, PM) were found, three of thirty-nine (7.69%) and one of thirty-nine (2.56%), respectively. Although, our results indicate that there is no found the CYP2C9*2. However, the variation of CYP2C9 allele might serve as a pharmacogenetics marker for screening before initiating the therapy with medical cannabis for the prevention of medical cannabis-induced AEs.

Keywords: CYP2C9, medical cannabis, adverse effects, THC, P450

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

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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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Authors: Anit S. Malhotra, Ajay Duseja, Neelam Chadha

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Endothelial dysfunction is a precursor to atherosclerosis, and flow-mediated dilatation (FMD) in the brachial artery is the commonest method to evaluate endothelial function in humans. Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver disorders encountered in clinical practice. An earlier meta-analysis had quantitatively assessed the degree of endothelial dysfunction using FMD. However, the largest study investigating the relation of FMD with NAFLD was published after that meta-analysis. In addition, that meta-analysis did not include some studies, including one from our centre. Therefore, an updating the previous meta-analysis was considered important. We searched PubMed, Cochrane Library, Embase, Scopus, SCI, Google Scholar, conference proceedings, and references of included studies till June 2017 to identify observational studies evaluating endothelial function using FMD in patients with non-alcoholic fatty liver disease. Data was analyzed using MedCalc. Fourteen studies were found eligible for inclusion in the meta-analysis. Patients with NAFLD had lower brachial artery FMD as compared to controls, standardized mean difference (random effects model) being –1.279%; 95% confidence interval (CI), –1.478 to –0.914. The effect size became smaller after addition of the recent study with the largest sample size was included compared with the earlier meta-analysis. In conclusion, patients with NAFLD had low FMD values indicating that they are at a higher risk of cardiovascular disease although our results suggest the effect size is not as large as reported previously.

Keywords: endothelial dysfunction, flow-mediated dilatation, meta-analysis, non-alcoholic fatty liver disease

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Authors: Tansa Nisan Gunerhan

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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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Authors: Han-Qin Zheng, Yi-Fan Chiang-Hsieh, Chia-Hung Chien, Wen-Chi Chang

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As the most important non-vascular plants, algae have many research applications, including high species diversity, biofuel sources, adsorption of heavy metals and, following processing, health supplements. With the increasing availability of next-generation sequencing (NGS) data for algae genomes and transcriptomes, an integrated resource for retrieving gene expression data and metabolic pathway is essential for functional analysis and systems biology in algae. However, gene expression profiles and biological pathways are displayed separately in current resources, and making it impossible to search current databases directly to identify the cellular response mechanisms. Therefore, this work develops a novel AlgaePath database to retrieve gene expression profiles efficiently under various conditions in numerous metabolic pathways. AlgaePath, a web-based database, integrates gene information, biological pathways, and next-generation sequencing (NGS) datasets in Chlamydomonasreinhardtii and Neodesmus sp. UTEX 2219-4. Users can identify gene expression profiles and pathway information by using five query pages (i.e. Gene Search, Pathway Search, Differentially Expressed Genes (DEGs) Search, Gene Group Analysis, and Co-Expression Analysis). The gene expression data of 45 and 4 samples can be obtained directly on pathway maps in C. reinhardtii and Neodesmus sp. UTEX 2219-4, respectively. Genes that are differentially expressed between two conditions can be identified in Folds Search. Furthermore, the Gene Group Analysis of AlgaePath includes pathway enrichment analysis, and can easily compare the gene expression profiles of functionally related genes in a map. Finally, Co-Expression Analysis provides co-expressed transcripts of a target gene. The analysis results provide a valuable reference for designing further experiments and elucidating critical mechanisms from high-throughput data. More than an effective interface to clarify the transcript response mechanisms in different metabolic pathways under various conditions, AlgaePath is also a data mining system to identify critical mechanisms based on high-throughput sequencing.

Keywords: next-generation sequencing (NGS), algae, transcriptome, metabolic pathway, co-expression

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

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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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Authors: Muna A. Eissawi, Safaa Abed Elfataah, Haytham Hago, Fatima E Abukunna, Ibtisam Amin Goreish, Nahid Gornas

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The study examined and analyzed the genetic diversity of DRB1locus of exon 2 of major histocompatibility complex of Sudanese desert sheep using PCR-RFLP and DNA sequencing. Five hundred samples belonging to five ecotypes of Desert Sudanese sheep (Abrag (Ab), Ashgar (Ash), Hamari (H), Kabashi (K) and Watish (W) were included. Amplification of exon 2 of the DRB1 gene yielded (300bp) amplified product in different ecotypes. Nine different digestion patterns corresponding to Five distinct alleles were observed with Rsa1 digestion. Genotype (ag) was the most common among all ecotypes, with a percentage comprised (40.4 %). The Hardy-Weinberg equilibrium (HWE) test showed that the studied ecotypes have significantly deviated from the theoretical proportions of Rsa1 patterns; probability values of the Chi-square test for HWE for MHC-DRB1 gene in SDS were 0.00 in all ecotypes. The constructed phylogenetic tree revealed the relation of 22 Sudanese isolates with each other and showed the shared sequences with 47 published foreign sequences randomly selected from different geographic regions. The results of this study highlight the effect of heterozygosity of MHC genes of the Desert sheep of Sudan which may clarify some of genetic back ground of their disease resistance and adaptation to environment.

Keywords: desert sheep, MHC, Ovar-DRB1, polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP)

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Authors: Philippa Saunders, Claire Fletcher

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INTRODUCTION: Prostate cancer is the most prevalent malignancy affecting Western males. It is initially an androgen-dependent disease: androgens bind to the androgen receptor and drive the expression of genes that promote proliferation and evasion of apoptosis. Despite reduced androgen dependence in advanced prostate cancer, androgen receptor signaling remains a key driver of growth. Androgen deprivation therapy (ADT) is, therefore, a first-line treatment approach and works well initially, but resistance inevitably develops. Abiraterone and Enzalutamide are drugs widely used in ADT and are androgen synthesis and androgen receptor signaling inhibitors, respectively. The shortage of other treatment options means acquired resistance to these drugs is a major clinical problem. MicroRNAs (miRs) are important mediators of post-transcriptional gene regulation and show altered expression in cancer. Several have been linked to the development of resistance to ADT. Manipulation of such miRs may be a pathway to breakthrough treatments for advanced prostate cancer. This study aimed to validate ADT resistance-implicated miRs and their clinically relevant targets. MATERIAL AND METHOD: Small RNA-sequencing of Abiraterone- and Enzalutamide-resistant C42 prostate cancer cells identified subsets of miRs dysregulated as compared to parental cells. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was used to validate altered expression of candidate ADT resistance-implicated miRs 195-5p, 497-5p and 29a-5p in ADT-resistant and -responsive prostate cancer cell lines, patient-derived xenografts (PDXs) and primary prostate cancer explants. RESULTS AND DISCUSSION: This study suggests a possible role for miR-497-5p in the development of ADT resistance in prostate cancer. MiR-497-5p expression was increased in ADT-resistant versus ADT-responsive prostate cancer cells. Importantly, miR-497-5p expression was also increased in Enzalutamide-treated, castrated (ADT-mimicking) PDXs versus intact PDXs. MiR-195-5p was also elevated in ADT-resistant versus -responsive prostate cancer cells, while there was a drop in miR-29a-5p expression. Candidate clinically relevant targets of miR-497-5p in prostate cancer were identified by mining AGO-PAR-CLIP-seq data sets and may include AVL9 and FZD6. CONCLUSION: In summary, this study identified microRNAs that are implicated in prostate cancer resistance to androgen deprivation therapy and could represent novel therapeutic targets for advanced disease.

Keywords: microRNA, androgen deprivation therapy, Enzalutamide, abiraterone, patient-derived xenograft

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Authors: Omaima A. Sharaf, Wafaa M. Abd El-Rahim, Hassan Moawad, Michael J. Sadowsky

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Textile industry is one of the important industries in the worldwide. It is known that the eco-friendly industrial and agricultural activities are significant for socio-economic stability of all countries. The absence of appropriate industrial waste water treatments is essential barrier for sustainable development in food and agricultural sectors especially in developing country like Egypt. Thus, the development of enzymatic bioremediation technology for textile dye removal will enhance the collaboration between scientists who develop the technology and industry where this technology will be implemented towards the safe disposal of the textile dye wastes. Highly efficient microorganisms are of most importance in developing and using highly effective biological treatment processes. Bacterial degradation of azo dyes is generally initiated by an enzymatic step that involves cleavage of azo linkages, usually with the aid of an azoreductase as electron donor. Thus, expanding the spectrum of microorganisms with high enzymatic activities as azoreductases and discovering novel azo-dye degrading enzymes, with enhanced stability and superior catalytic properties, are necessary for many environmental and industrial applications. Consequently, the use of molecular tools has become increasingly integrated into the understanding of enzyme properties and characterization. Researchers have utilized a gene cloning and expression methods as a tool to produce recombinant protein for decolorizing dyes more efficiently. Thus, presumptive evidence for the presence of genes encoding azoreductases in the genomes of selected local, and most potent azo-degrading strains were obtained by using specific oligonucleotides primers. These potent strains have been isolated from textile industrial wastewater in Egypt and identified using 16S rRNA sequence analysis as 'Lysinibacillus macrolidesB8, Brevibacillus parabrevisB11, Bacillus coagulansB7, and B. cereusB5'. PCR products of two full length genes designated as (AZO1;621bp and AZO2;534bp) were detected. BLASTx results indicated that AZO1 gene was corresponding to predicted azoreductase from of Bacillus sp. ABP14, complete genome, multispecies azoreductase [Bacillus], It was submitted to the gene bank by an accession no., BankIt2085371 AZO1 MG923210 (621bp; 207 amino acids). AZO1 was generated from the DNA of our identified strains Lysinibacillus macrolidesB8. On the other hand, AZO2 gene was corresponding to a predicted azoreductase from Bacillus cereus strain S2-8. Gene bank accession no. was BankIt2085839 AZO2 MG932081 (534bp;178 amino acids) and it was amplified from our Bacillus coagulansB7. Both genes were successfully cloned into pCR2.1TOPO (Invitrogen) and in pET28b+ vectors, then they transformed into E. coli DH5α and BL21(DE3) cells for heterologous expression studies. Our recombinant azoreductases (AZO1&AZO2) exhibited potential enzyme activity and efficiently decolorized an azo dye (Direct violet). They exhibited pH stability between 6 and 8 with optimum temperature up to 60°C and 37 °C after induction by 1mM and 1.5mM IPTG, for both AZO1 &AZO2, respectively. These results suggested that further optimization and purification of these recombinant proteins by using different heterologous expression systems will give great potential for the sustainable utilization of these recombinant enzymes in several industrial applications especially in wastewater treatments.

Keywords: azoreductases, decolorization, enzyme activity, gene cloning and expression

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

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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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Authors: Zohreh Rostami, Arezoo Khosravi, Mohammad Nikpoor Aghdam, Mahmood Salesi

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Background: Cardiovascular mortality in chronic kidney disease (CKD) and end stage renal disease (ESRD) patients have a strong relationship with baseline or progressive left ventricular hypertrophy (LVH) meanwhile in hemodialysis patients 10% decrement in left ventricular mass was associated with 28% reduction in cardiovascular mortality risk. In consonance with these arguments, we designed a study to measure morphological and functional echocardiographic variations early after transplantation. Method: The patients with normal renal function underwent two advanced echocardiographic studies to examine the structural and functional changes in left ventricular mass before and 3-month after transplantation. Results: From a total of 23 participants 21(91.3%) presented with left ventricular hypertrophy, 60.9% in eccentric and 30.4% in concentric group. Diastolic dysfunction improved in concentric group after transplantation. Both in pre and post transplantation global longitudinal strain (GLS)- average in eccentric group was more than concentric (-17.45 ± 2.75 vs -14.3 ± 3.38 p=0.03) and (-18.08 ± 2.6 vs -16.1 ± 2.7 p= 0.04) respectively. Conclusion: Improvement and recovery of left ventricular function in concentric group was better and sooner than eccentric after kidney transplantation. Although fractional shortening and diastolic function and GLS-4C in pre-transplantation in concentric group was worse than eccentric, but therapeutic response to kidney transplantation in concentric was more and earlier than eccentric group.

Keywords: chronic kidney disease, end stage renal disease, left ventricular hypertrophy, global longitudinal strain

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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

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

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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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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: E. Akdur Öztürk, F. İrvasa Bilgiç, A. Ludovisi , O. Gülbahar, D. Dirim Erdoğan, M. Korkmaz, M. Á. Gómez Morales

Abstract:

Anisakidosis is a zoonotic human fish-borne parasitic disease caused by accidental ingestion of anisakid third-stage larvae (L3) of members of the Anisakidae family present in infected marine fish or cephalopods. Infection with anisakid larvae can lead to gastric, intestinal, extra-gastrointestinal and gastroallergic forms of the disease. Anisakid parasites have been reported in almost all seas, particularly in the Mediterranean Sea. There is a remarkably high level of risk exposure to these zoonotic parasites as they are present in economically and ecologically important fish of Europe. Anisakid L3 larvae have been also detected in several fish species from the Aegean Sea. Turkey is a peninsular country surrounded by Black, Aegean and the Mediterranean Sea. In this country, fishing habit and fishery product consumption are highly common. In recent years, there was also an increase in the consumption of raw fish due to the increasing interest in the cuisine of the Far East countries. In different regions of Turkey, A. simplex (inMerluccius Merluccius Scomber japonicus, Trachurus mediterraneus, Sardina pilchardus, Engraulis encrasicolus, etc.), Anisakis spp., Contraceucum spp., Pseudoterronova spp. and, C. aduncum were identified as well. Although it is accepted both the presence of anisakid parasites in fish and fishery products in Turkey and the presence of Turkish people with allergic manifestations after fish consumption, there are no reports of human anisakiasis in this country. Given the high prevalence of anisakid parasites in the country, the absence of reports is likely not due to the absence of clinical cases rather to the unavailability of diagnostic tools and the low awareness of the presence of this infection. The aim of the study was to set up an IgE-Western Blot (WB) based test to detect the anisakidosis sensitization among Turkish people with a history of allergic manifestation related to fish consumption. To this end, crude worm antigens (CWA) and allergen enriched fraction (50-66% ) were prepared from L3 of A. simplex (s.l.) collected from Lepidopus caudatus fished in the Mediterranean Sea. These proteins were electrophoretically separated and transferred into the nitrocellulose membranes. By WB, specific proteins recognized by positive control serum samples from sensitized patients were visualized on nitrocellulose membranes by a colorimetric reaction. The CWA and 50–66% fraction showed specific bands, mainly due to Ani s 1 (20-22 kD) and Ani s 4 (9-10 kD). So far, a total of 7 serum samples from people with allergic manifestation and positive skin prick test (SPT) after fish consumption, have been tested and all of them resulted negative by WB, indicating the lack of sensitization to anisakids. This preliminary study allowed to set up a specific test and evidence the lack of correlation between both tests, SPT and WB. However, the sample size should be increased to estimate the anisakidosis burden in Turkish people.

Keywords: anisakidosis, fish parasite, serodiagnosis, Turkey

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Authors: Mariola Głowacka

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The aim of the study was to determine the level of adaptation to the current health situation and its impact on the adherence state of people in the pre- and senior age. The work covers the results of the first of the fourteen parts of the study conducted in a group of 2,000 people aged 55 plus. This part of the project was carried out with the use of two standardized tools: the HLC adaptation scale (the health locus of control scale and The Adherence in Chronic DiseasesScale (ACDS). The obtained results showed the range of influence of particular areas of self-acceptance of the health state (health and disease) on their adherence, taking into account specific clinical conditions.

Keywords: adaptation to the current health situation, adherence, senior, badania

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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: Khachen Kongpakwattana, Nathorn Chaiyakunapruk

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Background: Decision-analytic models for Alzheimer’s disease (AD) have been advanced to discrete-event simulation (DES), in which individual-level modelling of disease progression across continuous severity spectra and incorporation of key parameters such as treatment persistence into the model become feasible. This study aimed to apply the DES to perform a cost-effectiveness analysis of treatment for AD in Thailand. Methods: A dataset of Thai patients with AD, representing unique demographic and clinical characteristics, was bootstrapped to generate a baseline cohort of patients. Each patient was cloned and assigned to donepezil, galantamine, rivastigmine, memantine or no treatment. Throughout the simulation period, the model randomly assigned each patient to discrete events including hospital visits, treatment discontinuation and death. Correlated changes in cognitive and behavioral status over time were developed using patient-level data. Treatment effects were obtained from the most recent network meta-analysis. Treatment persistence, mortality and predictive equations for functional status, costs (Thai baht (THB) in 2017) and quality-adjusted life year (QALY) were derived from country-specific real-world data. The time horizon was 10 years, with a discount rate of 3% per annum. Cost-effectiveness was evaluated based on the willingness-to-pay (WTP) threshold of 160,000 THB/QALY gained (4,994 US$/QALY gained) in Thailand. Results: Under a societal perspective, only was the prescription of donepezil to AD patients with all disease-severity levels found to be cost-effective. Compared to untreated patients, although the patients receiving donepezil incurred a discounted additional costs of 2,161 THB, they experienced a discounted gain in QALY of 0.021, resulting in an incremental cost-effectiveness ratio (ICER) of 138,524 THB/QALY (4,062 US$/QALY). Besides, providing early treatment with donepezil to mild AD patients further reduced the ICER to 61,652 THB/QALY (1,808 US$/QALY). However, the dominance of donepezil appeared to wane when delayed treatment was given to a subgroup of moderate and severe AD patients [ICER: 284,388 THB/QALY (8,340 US$/QALY)]. Introduction of a treatment stopping rule when the Mini-Mental State Exam (MMSE) score goes below 10 to a mild AD cohort did not deteriorate the cost-effectiveness of donepezil at the current treatment persistence level. On the other hand, none of the AD medications was cost-effective when being considered under a healthcare perspective. Conclusions: The DES greatly enhances real-world representativeness of decision-analytic models for AD. Under a societal perspective, treatment with donepezil improves patient’s quality of life and is considered cost-effective when used to treat AD patients with all disease-severity levels in Thailand. The optimal treatment benefits are observed when donepezil is prescribed since the early course of AD. With healthcare budget constraints in Thailand, the implementation of donepezil coverage may be most likely possible when being considered starting with mild AD patients, along with the stopping rule introduced.

Keywords: Alzheimer's disease, cost-effectiveness analysis, discrete event simulation, health technology assessment

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

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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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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: Sofia Meacham

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In this abstract paper, the Domain-Specific Languages (DSL) evaluation will be presented based on existing literature and years of experience developing DSLs for several domains. The domains we worked on ranged from AI, business applications, and finances/accounting to health. In general, DSLs have been utilised in many domains to provide tailored and efficient solutions to address specific problems. Although they are a reputable method among highly technical circles and have also been used by non-technical experts with success, according to our knowledge, there isn’t a commonly accepted method for evaluating them. There are some methods that define criteria that are adaptations from the general software engineering quality criteria. Other literature focuses on the DSL usability aspect of evaluation and applies methods such as Human-Computer Interaction (HCI) and goal modeling. All these approaches are either hard to introduce, such as the goal modeling, or seem to ignore the domain-specific focus of the DSLs. From our experience, the DSLs have domain-specificity in their core, and consequently, the methods to evaluate them should also include domain-specific criteria in their core. The domain-specific criteria would require synergy between the domain experts and the DSL developers in the same way that DSLs cannot be developed without domain-experts involvement. Methods from agile and other software engineering practices, such as co-creation workshops, should be further emphasised and explored to facilitate this direction. Concluding, our latest experience and plans for DSLs evaluation will be presented and open for discussion.

Keywords: domain-specific languages, DSL evaluation, DSL usability, DSL quality metrics

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Authors: Akanksha Bhatnagar, Sandhya Kortegare, Felice Elefant

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Context: Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by progressive cognitive decline and memory loss. The cause of AD is not fully understood, but it is thought to be caused by a combination of genetic, environmental, and lifestyle factors. One of the hallmarks of AD is the loss of neurons in the hippocampus, a brain region that is important for memory and learning. This loss of neurons is thought to be caused by a decrease in histone acetylation, which is a process that regulates gene expression. Research Aim: The research aim of the study was to develop mall molecule compounds that can enhance the activity of Tip60, a histone acetyltransferase that is important for memory and learning. Methodology/Analysis: The researchers used in silico structural modeling and a pharmacophore-based virtual screening approach to design and synthesize small molecule compounds strongly predicted to target and enhance Tip60’s HAT activity. The compounds were then tested in vitro and in vivo to assess their ability to enhance Tip60 activity and rescue cognitive deficits in AD models. Findings: The researchers found that several of the compounds were able to enhance Tip60 activity and rescue cognitive deficits in AD models. The compounds were also developed to cross the blood-brain barrier, which is an important factor for the development of potential AD therapeutics. Theoretical Importance: The findings of this study suggest that Tip60 HAT activators have the potential to be developed as therapeutic agents for AD. The compounds are specific to Tip60, which suggests that they may have fewer side effects than other HDAC inhibitors. Additionally, the compounds are able to cross the blood-brain barrier, which is a major hurdle for the development of AD therapeutics. Data Collection: The study collected data from a variety of sources, including in vitro assays and animal models. The in vitro assays assessed the ability of compounds to enhance Tip60 activity using histone acetyltransferase (HAT) enzyme assays and chromatin immunoprecipitation assays. Animal models were used to assess the ability of the compounds to rescue cognitive deficits in AD models using a variety of behavioral tests, including locomotor ability, sensory learning, and recognition tasks. The human clinical trials will be used to assess the safety and efficacy of the compounds in humans. Questions: The question addressed by this study was whether Tip60 HAT activators could be developed as therapeutic agents for AD. Conclusions: The findings of this study suggest that Tip60 HAT activators have the potential to be developed as therapeutic agents for AD. The compounds are specific to Tip60, which suggests that they may have fewer side effects than other HDAC inhibitors. Additionally, the compounds are able to cross the blood-brain barrier, which is a major hurdle for the development of AD therapeutics. Further research is needed to confirm the safety and efficacy of these compounds in humans.

Keywords: Alzheimer's disease, cognition, neuroepigenetics, drug discovery

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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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