Search results for: disease association

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: Lia Mania, Ketevan Nanobashvili

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Background: The coronavirus disease COVID-19 has become the cause of a global health crisis during the current pandemic. This study aims to fill the paucity of epidemiological studies on the impact of COVID-19 on the oral health of pediatric populations. Methods: It was conducted an observational, cross-sectional study in Georgia, in Tbilisi (capital of Georgia), among 7 to 12-year-old PCR or rapid test-confirmed post-Covid populations in all districts of Tbilisi (10 districts in total). 332 beneficiaries who were infected with Covid within one year were included in the study. The population was selected in schools of Tbilisi according to the principle of cluster selection. A simple random selection took place in the selected clusters. According to this principle, an equal number of beneficiaries were selected in all districts of Tbilisi. By July 1, 2022, according to National Center for Disease Control and Public Health data (NCDC.Ge), the number of test-confirmed cases in the population aged 0-18 in Tbilisi was 115137 children (17.7% of all confirmed cases). The number of patients to be examined was determined by the sample size. Oral screening, microbiological examination of saliva, and administration of oral health questionnaires to guardians were performed. Statistical processing of data was done with SPSS-23. Risk factors were estimated by odds ratio and logistic regression with 95% confidence interval. Results: Statistically reliable differences between the averages of oral health indicators in asymptomatic and symptomatic covid-infected groups are: for caries intensity (DMF+def) t=4.468 and p=0.000, for modified gingival index (MGI) t=3.048, p=0.002, for simplified oral hygiene index (S-OHI) t=4.853; p=0.000. Symptomatic covid-infection has a reliable effect on the oral microbiome (Staphylococcus aureus, Candida albicans, Pseudomonas aeruginosa, Streptococcus pneumoniae, Staphylococcus epidermalis); (n=332; 77.3% vs n=332; 58.0%; OR=2.46, 95%CI: 1.318-4.617). According to the logistic regression, it was found that the severity of the covid infection has a significant effect on the frequency of pathogenic and conditionally pathogenic bacteria in the oral cavity B=0.903 AOR=2.467 (CL 1.318-4.617). Symptomatic covid-infection affects oral health indicators, regardless of the presence of other risk factors, such as parental employment status, tooth brushing behaviors, carbohydrate meal, fruit consumption. (p<0.05). Conclusion: Risk factors (parental employment status, tooth brushing behaviors, carbohydrate consumption) were associated with poorer oral health status in a post-Covid population of 7- to 12-year-old children. However, such a risk factor as symptomatic ongoing covid-infection affected the oral microbiome in terms of the abundant growth of pathogenic and conditionally pathogenic bacteria (Staphylococcus aureus, Candida albicans, Pseudomonas aeruginosa, Streptococcus pneumoniae, Staphylococcus epidermalis) and further worsened oral health indicators. Thus, a close association was established between symptomatic covid-infection and microbiome changes in the post-covid period; also - between the variables of oral health indicators and the symptomatic course of covid-infection.

Keywords: oral microbiome, COVID-19, population based research, oral health indicators

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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: Lukman Ahmad Jamil, Heather M. Wallace

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Introduction: Numerous epidemiological studies have shown a positive as well as negative association and no association in some cases between chronic use of calcium channel blockers and the increased risk of developing cancer. However, these associations were enmeshed with controversies in the absence of laboratory based studies to back up those claims. Aim: The aim of this study was to determine in mechanistic terms the association between the long-term administration of nifedipine and diltiazem and increased risk of developing cancer using the human embryonic kidney (HEK293) cell line. Methods: Cell counting using the Trypan blue dye exclusion and 3-4, 5-Dimethylthiazol-2-yl-2, 5-diphenyl-tetrazolium bromide (MTT) assays were used to investigate the effect of nifedipine and diltiazem on the growth pattern of HEK293 cells. Protein assay using modified Lowry method and analysis of intracellular polyamines concentration using Liquid Chromatography – Tandem Mass Spectrometry (LC-MS) were performed to ascertain the mechanism through which chronic use of nifedipine increases the risk of developing cancer. Results: Both nifedipine and diltiazem significantly increased the proliferation of HEK293 cells dose and time dependently. This proliferative effect after 24, 48 and 72-hour incubation period was observed at 0.78, 1.56 and 25 µM for nifedipine and 0.39, 1.56 and 25 µM for diltiazem, respectively. The increased proliferation of the cells was found to be statistically significantly (p<0.05). Furthermore, the increased proliferation of the cells induced by nifedipine was associated with the increase in the protein content and elevated intracellular polyamines concentration level. Conclusion: The chronic use of nifedipine is associated with increased proliferation of cells with concomitant elevation of polyamines concentration and elevated polyamine levels have been implicated in many malignant transformations and hence, these provide a possible explanation on the link between long term use of nifedipine and development of some human cancers. Further studies are needed to evaluate the cause of this association.

Keywords: cancer, nifedipine, polyamine, proliferation

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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: 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: Mengying Wang, Dongjing Liu, Holger Schwender, Ping Wang, Hongping Zhu, Tao Wu, Terri H Beaty

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Background: Maternal smoking is a recognized risk factor for nonsyndromic cleft lip with or without cleft palate (NSCL/P). It has been reported that the effect of maternal smoking on oral clefts is mediated through genes that influence nicotine dependence. The polymorphisms of cholinergic receptor nicotinic alpha (CHRNA) and beta (CHRNB) subunits genes have previously shown strong associations with nicotine dependence. Here, we attempted to investigate whether the above genes are associated with clefting risk through testing for potential gene-gene (G×G) and gene-environment (G×E) interaction. Methods: We selected 120 markers in 14 genes associated with nicotine dependence to conduct transmission disequilibrium tests among 806 Chinese NSCL/P case-parent trios ascertained in an international consortium which conducted a genome-wide association study (GWAS) of oral clefts. We applied Cordell’s method using “TRIO” package in R to explore G×G as well as G×E interaction involving environmental tobacco smoke (ETS) based on conditional logistic regression model. Results: while no SNP showed significant association with NSCL/P after Bonferroni correction, we found signals for G×G interaction between 10 pairs of SNPs in CHRNA3, CHRNA5, and CHRNB4 (p<10-8), among which the most significant interaction was found between RS3743077 (CHRNA3) and RS11636753 (CHRNB4, p<8.2×10-12). Linkage disequilibrium (LD) analysis revealed only low level of LD between these markers. However, there were no significant results for G×ETS interaction. Conclusion: This study fails to detect association between nicotine dependence genes and NSCL/P, but illustrates the importance of taking into account potential G×G interaction for genetic association analysis in NSCL/P. This study also suggests nicotine dependence genes should be considered as important candidate genes for NSCL/P in future studies.

Keywords: Gene-Gene Interaction, Maternal Smoking, Nicotine Dependence, Non-Syndromic Cleft Lip with or without Cleft Palate

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Authors: S. Mohd Afzal, R. O'Connell

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Kaposi's sarcoma (KS) is the most common HIV-related cancer, and ocular manifestations constitute at least 25% of all KS cases. However, ocular presentations often occur in the context of systemic KS, and isolated lesions are rare. We report a unique case of ocular KS masquerading as subconjunctival haemorrhage, and only developing systemic manifestations after initiation of HIV treatment. Case: A 49-year old man with previous hypertensive stroke and newly diagnosed HIV infection presented with an acutely red left eye following repeated bouts of coughing. Given the convincing history of poorly controlled hypertension and cough, a diagnosis of subconjunctival haemorrhage was made. Over the next week, his ocular lesion began to improve and he subsequently started anti-retroviral therapy. Prior to receiving anti-retroviral therapy, his CD4+ lymphocyte count was 194 cells/mm3 with HIV viral load greater than 1 million/ml. This rapidly improved to a viral load of 150 copies/ml within 2 weeks of starting treatment. However, a few days after starting HIV treatment, his ocular lesion recurred. Ophthalmic examination was otherwise normal. He also developed widespread lymphadenopathy and multiple dark lesions on his torso. Histology and virology confirmed KS, systemically triggered by Immune Reconstitution Syndrome (KS-IRIS). The patient has since undergone chemotherapy successfully. Discussion: Kaposi's sarcoma is an atypical tumour caused by human herpesvirus 8 (HHV-8), also known as Kaposi’s sarcoma-associated herpesvirus (KSHV). In immunosuppressed patients, KSHV can also cause lymphoproliferative disorders such as primary effusion lymphoma and Castleman's disease (in our patient’s case, this was excluded through histological analysis of lymph nodes). KSHV is one of the seven currently known human oncoviruses, and its pathogenesis is poorly understood. Up to 13% of patients with HIV-related KS experience worsening of the disease after starting anti-retroviral treatment, due to a sudden increase in CD4 cell counts. Histology remains the diagnostic gold standard. Current British HIV Association (BHIVA) guidelines recommend treatment using anti-retroviral drugs, with either intralesional vinblastine for local disease or systemic chemotherapy for disseminated KS. Conclusion: This case is unique as ocular KS as initial presentation is rare and our patient's diagnosis was only made after systemic lesions were triggered by immune reconstitution. KS should be considered as an important differential diagnosis for red eyes in all patients at risk of acquiring HIV infection.

Keywords: human herpesvirus 8, human immunodeficiency virus, immune reconstitution syndrome, Kaposi’s sarcoma, Kaposi’s sarcoma-associated herpesvirus

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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: Adam Chlapecka, Anna Kagstrom, Pavla Cermakova

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Background: Increasing educational attainment (EA) could decrease the occurrence of depression. We investigated the relationship between EA and depressive symptoms in older individuals across four European regions. Methods: We studied 108 315 Europeans (54 % women, median age 63 years old) from the Survey on Health, Ageing and Retirement in Europe assessing EA (7 educational levels based on ISCED classification); and depressive symptoms (≥ 4 points on EURO-D scale). Logistic regression estimated the association between EA and depressive symptoms, adjusting for sociodemographic and health-related factors; testing for sex/age/region and education interactions. Results: Higher EA was associated with lower odds of depressive symptoms, independent of sociodemographic and health-related factors. A threshold of the lowest odds of depressive symptoms was detected at the first stage of tertiary education (OR 0.60; 95% CI 0.55-0.65; p<0.001; relative to no education). Central and Eastern Europe showed the strongest association (OR for high vs. low education 0.37; 95% CI 0.33-0.40; p<0.001) and Scandinavia the weakest (OR for high vs. low education 0.69; 95% CI 0.60-0.80; p<0.001). The association was strongest amongst younger individuals. There was a sex and education interaction only within Central and Eastern Europe. Conclusion: The level of EA is reflected in later-life depressive symptoms, suggesting that supporting individuals in achieving EA, and considering those with lower EA at increased risk for depression, could lead to the decreased burden of depression across the life course. Further educational support in Central and Eastern Europe may decrease the higher burden of depressive symptoms in women.

Keywords: depression, education, epidemiology, Europe

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Authors: Ghaleb Bin Huraib, Fahad Al Harthi, Mohammad Mustafa, Abdulrahman Al-Asmari

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Introduction: Vitiligo is an acquired pigmentary skin disorder with the regional disappearance of melanocytes. Vitiligo affects 0.1 to 2% of the global population, and the incidence varies substantially depending on ethnicity. Glutathione S-transferase (GST) is a multigene family of enzymes that detoxify oxidative stress products. The oxidative stress-related GSTM1/GSTT1 genes deletion may cause epidermal melanocytes destruction and the development of vitiligo. Hence, the present study aimed to investigate the association of GST gene polymorphisms with vitiligo in the Saudi population, if any. Materials and Methods: The present study includes 129 vitiligo cases and 130 age-matched healthy controls. The proportion of male and female patients with vitiligo is almost equal. The multiplex polymerase chain reaction (PCR) method was used for polymorphic analysis. Results: Increased odds of generalized vitiligo was observed with the null genotypes of GSTT1- gene (OR = 1.91, 95% CI = 1.07-3.42, p = 0.019). The possible genetic combinations of GSTM1/GSTT1 and their genotypic distribution showed the frequency of GSTM1+/GSTT1+ 62/130 (47.69%) and GSTM1-/GSTT1+ 52/130 (40.00%) were higher in controls than in cases 44/129 (34.11%), 43/129 (33.34%), respectively while GSTM1+/GSTT1- and GSTM1-/GSTT1- null genotypes were higher 22/129 (17.05%) and 20/129 (15.50%) in vitiligo patients as compared to controls 11/130 (8.46%), 5/130 (3.84%), respectively. The strength of association of different genetic combinations with cases have shown GSTM1+/GSTT1- (OR = 2.81, 95% CI = 1.24-6.40, p = 0.009) and GSTM1-/GSTT1- (OR = 5.63, 95% CI = 1.96 - 16.16, p = 0.0004) were significantly higher in vitiligo cases as compared to controls. We did not observe any significant association of age and gender of patients with GST gene polymorphisms. Conclusions: The GSTT1-, GSTM1+/GSTT1- and GSTM1-/GSTT1- null genotypes were significantly associated with vitiligo. These genetic polymorphisms may be the associative genetic risk factor for vitiligo among Saudis. It could be used as a genetic marker for screening vitiligo patients among Saudis. Further studies on GSTs gene polymorphism in larger sample sizes from different geographical areas and ethnicity are needed to strengthen the present findings.

Keywords: vitiligo, GSTM1, GSTT1, gene polymorphism, oxidative stress

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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: Robyn Heitzman

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The traditional method of punitive justice in Brazil has failed to prevent high levels of recidivism. Combined with overcrowding, a lack of resources, and human rights abuses, the conventional prison approach in Brazil is being questioned; one alternative approach is the association of protection and assistance to convicts (APAC) method. Justice -according to the principles of the APAC methodology- is served through education, reformation, and human development. The model has reported relatively low levels of recidivism and has been internationally recognised for its progress. Through qualitative research such as interviews and case studies, this paper explains why, applying the theory of restorative justice, the APAC methodology yields lower rates of recidivism compared to the traditional models of prisons in Brazil. 

Keywords: Brazil, justice, prisons, restorative

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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: Zaky Musyarof, Dwi Yono Sutarto, Dwima Rindy Atika, R. B. Fajriya Hakim

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Each country should be responsible for the safety of people, especially responsible for the safety of people living in disaster-prone areas. One of those services is provides evacuation route for them. But all this time, the selection of evacuation route is seem doesn’t well organized, it could be seen that when a disaster happen, there will be many accumulation of people on the steps of evacuation route. That condition is dangerous to people because hampers evacuation process. By some methods in Statistical analysis, author tries to give a suggestion how to prepare evacuation route which is organized and based on people habit. Those methods are association rules, sequential pattern mining, hierarchical cluster analysis and fuzzy logic.

Keywords: association rules, sequential pattern mining, cluster analysis, fuzzy logic, evacuation route

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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: Mythri G., Manjunath ML, Girish Babu M., Shireen Swaliha Quadri

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Background: The increase in diabetes among the elderly is of concern because in addition to the wide range of traditional diabetes complications, evidence has been growing that diabetes is associated with increased risk of cognitive decline. Aims and Objectives: To find out if there is any association between blood sugar levels and short-term and working memory status in patients of type 2 diabetes. Materials and Methods: The study was carried out in 200 individuals aged between 40-65 years consisting of 100 diagnosed cases of Type 2 Diabetes Mellitus and 100 non-diabetics from OPD of Mc Gann Hospital, Shivamogga. Rye’s Auditory Verbal Learning Test, Verbal Fluency Test and Visual Reproduction Test, Working Digit Span Test and Validation Span Test were used to assess short-term and working memory. Fasting and Post Prandial blood sugar levels were estimated. Statistical analysis was done using SPSS 21. Results: Memory test scores of type 2 diabetics were significantly reduced (p < 0.001) when compared to the memory scores of age and gender matched non-diabetics. Fasting blood sugar levels were found to have a negative correlation with memory scores for all 5 tests: AVLT (r=-0.837), VFT (r=-0.888), VRT(r=-0.787), WDST (r=-0.795) and VST (r=-0.943). Post- Prandial blood sugar levels were found to have a negative correlation with memory scores for all 5 tests: AVLT (r=-0.922), VFT (r=-0.848), VRT(r=-0.707),WDST (r=-0.729) and VST (r=-0.880) Memory scores in all 5 tests were found to be negatively correlated with the FBS and PPBS levels in diabetic patients (p < 0.001). Conclusion: The decreased memory status in diabetic patients may be due to many factors like hyperglycemia, vascular disease, insulin resistance, amyloid deposition and also some of the factor combine to produce additive effects like, type of diabetes, co-morbidities, age of onset, duration of the disease and type of therapy. These observed effects of blood sugar levels of diabetics on memory status are of potential clinical importance because even mild cognitive impairment could interfere with todays’ activities.

Keywords: diabetes, cognition, diabetes, HRV, respiratory medicine

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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: Dhananjay W. Bansod, Santosh Phad

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Non-Communicable Diseases (NCD) are major contributing factors to the disease burden in the world as well as in India. With a growing proportion of older persons in India gives rise to several challenges. With the advancement of age, elderly is exposed to various kinds of health problems more specifically NCDs. Therefore, an effort has been made to examine the prevalence of NCDs among older persons and its treatment-seeking behaviour, also it is tried to explore the association between the NCDs and its effect on the overall wellbeing of older persons. Data used from “Building Knowledge Base of Population Ageing Survey” conducted in 2011 in seven states of India. Six chronic diseases used (non-communicable diseases) namely Arthritis, Hypertension, Cataract, Diabetes, Asthma and Heart diseases to understand the issues related to NCDs. Also seen the effect of NCDs on the wellbeing of the elderly, the subjective well-being consists of nine questions from which SUBI score generated for mental health status, which ranges from 9 to 27. This Index indicates that lower the score better is the mental health status. Further, this index modified and generated three categories of Better (9-15), Average (16-20) and Worse (21-27). The reliability analysis is carried out with the coefficient (Cronbach’s alpha) of the scale was 0.8884. The result shows that Orthopedic / musculoskeletal ailments involving arthritis, rheumatism and osteoarthritis are the most common type of ailment followed by hypertension. Two-thirds of the elderly reported suffering from at least one chronic ailment. Most chronic illness conditions received some form of treatment and mainly depend on public health facilities. Financial insecurity is the primary obstruction in seeking treatment for most of the chronic ailments which typically require a longer duration of medication and repeated medical consultations, both having significant economic implications. According to SUBI index, only 15 per cent of the elderly are in Better mental health status, and one-third of the elderly are with the worse score. Elderly with the ailments like Cataract, Asthma and Arthritis have worse mental health. It depicts that the burden of disease is more among the elderly and it is directly affecting the overall wellbeing of older persons.

Keywords: NCD, well-being, older person, India

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Authors: Ammaarah Gamieldien

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Depression is a very common and serious mental illness that has a significant impact on both the social and economic aspects of sufferers worldwide. This study aimed to investigate the association between body mass index (BMI), blood pressure, and lipid profiles with mental health symptoms in university students. Secondary objectives included the associations between the variables (BMI, blood pressure, and lipids) with themselves, as they are key factors in cardiometabolic disease. Sixty-three (63) students participated in the study. Thirty-two (32) were assigned to the control group (minimal-mild depressive symptoms), while 31 were assigned to the depressive group (moderate to severe depressive symptoms). Montgomery-Asberg Depression Rating Scale (MADRS) and Beck Depression Inventory (BDI) were used to assess depressive scores. Anthropometric measurements such as weight (kg), height (m), waist circumference (WC), and hip circumference were measured. Body mass index (BMI) and ratios such as waist-to-hip ratio (WHR) and waist-to-height ratio (WtHR) were also calculated. Blood pressure was measured using an automated AfriMedics blood pressure machine, while lipids were measured using a CardioChek plus analyzer machine. Statistics were analyzed via the SPSS statistics program. There were no significant associations between anthropometric measurements and depressive scores (p > 0.05). There were no significant correlations between lipid profiles and depression when running a Spearman’s rho correlation (P > 0.05). However, total cholesterol and LDL-C were negatively associated with depression, and triglycerides were positively associated with depression after running a point-biserial correlation (P < 0.05). Overall, there were no significant associations between blood pressure measurements and depression (P > 0.05). However, there was a significant moderate positive correlation between systolic blood pressure and MADRS scores in males (P < 0.05). Depressive scores positively and strongly correlated to how long it takes participants to fall asleep. There were also significant associations with regard to the secondary objectives. This study indicates the importance of determining the prevalence of depression among university students in South Africa. If the prevalence and factors associated with depression are addressed, depressive symptoms in university students may be improved.

Keywords: depression, blood pressure, body mass index, lipid profiles, mental health symptoms

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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: Seema Vaidya

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Mining association rule is a key issue in data mining. In any case, the standard models ignore the distinction among the exchanges, and the weighted association rule mining does not transform on databases with just binary attributes. This paper proposes a novel continuous example and executes a tree (FP-tree) structure, which is an increased prefix-tree structure for securing compacted, discriminating data about examples, and makes a fit FP-tree-based mining system, FP enhanced capacity algorithm is used, for mining the complete game plan of examples by illustration incessant development. Here, this paper handles the motivation behind making remarkable and weighted item sets, i.e. rare weighted item set mining issue. The two novel brightness measures are proposed for figuring the infrequent weighted item set mining issue. Also, the algorithm are handled which perform IWI which is more insignificant IWI mining. Moreover we utilized the rare item set for choice based structure. The general issue of the start of reliable definite rules is troublesome for the grounds that hypothetically no inciting technique with no other person can promise the rightness of influenced theories. In this way, this framework expects the disorder with the uncommon signs. Usage study demonstrates that proposed algorithm upgrades the structure which is successful and versatile for mining both long and short diagnostics rules. Structure upgrades aftereffects of foreseeing rare diseases of patient.

Keywords: association rule, data mining, IWI mining, infrequent item set, frequent pattern growth

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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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