Search results for: metabolic disease
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4215

Search results for: metabolic disease

4005 Vaccine Development for Newcastle Disease Virus in Poultry

Authors: Muhammad Asif Rasheed

Abstract:

Newcastle disease virus (NDV), an avian orthoavulavirus, is a causative agent of Newcastle disease named (NDV) and can cause even the epidemics when the disease is not treated. Previously several vaccines based on attenuated and inactivated viruses have been reported, which are rendered useless with the passage of time due to versatile changes in viral genome. Therefore, we aimed to develop an effective multi-epitope vaccine against the haemagglutinin neuraminidase (HN) protein of 26 NDV strains from Pakistan through a modern immunoinformatic approaches. As a result, a vaccine chimaera was constructed by combining T-cell and B-cell epitopes with the appropriate linkers and adjuvant. The designed vaccine was highly immunogenic, non-allergen, and antigenic; therefore, the potential 3D-structureof multi epitope vaccine was constructed, refined, and validated. A molecular docking study of a multiepitope vaccine candidate with the chicken Toll-like receptor-4 indicated successful binding. An In silico immunological simulation was used to evaluate the candidate vaccine's ability to elicit an effective immune response. According to the computational studies, the proposed multiepitope vaccine is physically stable and may induce immune responses, whichsuggested it a strong candidate against 26 Newcastle disease virus strains from Pakistan. A wet lab study is under process to confirm the results.

Keywords: epitopes, newcastle disease virus, paramyxovirus virus, vaccine

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4004 Evaluation of Mito-Uncoupler Induced Hyper Metabolic and Aggressive Phenotype in Glioma Cells

Authors: Yogesh Rai, Saurabh Singh, Sanjay Pandey, Dhananjay K. Sah, B. G. Roy, B. S. Dwarakanath, Anant N. Bhatt

Abstract:

One of the most common signatures of highly malignant gliomas is their capacity to metabolize more glucose to lactic acid than normal brain tissues, even under normoxic conditions (Warburg effect), indicating that aerobic glycolysis is constitutively upregulated through stable genetic or epigenetic changes. However, oxidative phosphorylation (OxPhos) is also required to maintain the mitochondrial membrane potential for tumor cell survival. In the process of tumorigenesis, tumor cells during fastest growth rate exhibit both high glycolytic and high OxPhos. Therefore, metabolically reprogrammed cancer cells with combination of both aerobic glycolysis and altered OxPhos develop a robust metabolic phenotype, which confers a selective growth advantage. In our study, we grew the high glycolytic BMG-1 (glioma) cells with continuous exposure of mitochondrial uncoupler 2, 4, dinitro phenol (DNP) for 10 passages to obtain a phenotype of high glycolysis with enhanced altered OxPhos. We found that OxPhos modified BMG (OPMBMG) cells has similar growth rate and cell cycle distribution but high mitochondrial mass and functional enzymatic activity than parental cells. In in-vitro studies, OPMBMG cells showed enhanced invasion, proliferation and migration properties. Moreover, it also showed enhanced angiogenesis in matrigel plug assay. Xenografted tumors from OPMBMG cells showed reduced latent period, faster growth rate and nearly five folds reduction in the tumor take in nude mice compared to BMG-1 cells, suggesting that robust metabolic phenotype facilitates tumor formation and growth. OPMBMG cells which were found radio-resistant, showed enhanced radio-sensitization by 2-DG as compared to the parental BMG-1 cells. This study suggests that metabolic reprogramming in cancer cells enhances the potential of migration, invasion and proliferation. It also strengthens the cancer cells to escape the death processes, conferring resistance to therapeutic modalities. Our data also suggest that combining metabolic inhibitors like 2-DG with conventional therapeutic modalities can sensitize such metabolically aggressive cancer cells more than the therapies alone.

Keywords: 2-DG, BMG, DNP, OPM-BMG

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4003 Endothelial Progenitor Cell Biology in Ankylosing Spondylitis

Authors: Ashit Syngle, Inderjit Verma, Pawan Krishan

Abstract:

Aim: Endothelial progenitor cells (EPCs) are unique populations which have reparative potential in overcoming the endothelial damage and reducing cardiovascular risk. Patients with ankylosing spondylitis (AS) have increased risk of cardiovascular morbidity and mortality. The aim of this study was to investigate the endothelial progenitor cell population in AS patients and its potential relationships with disease variables. Methods: Endothelial progenitor cells were measured in peripheral blood samples from 20 AS and 20 healthy controls by flow cytometry on the basis of CD34 and CD133 expression. Disease activity was evaluated by using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Functional ability was monitored by using Bath Ankylosing Spondylitis Functional Index (BASFI). Results: EPCs were depleted in AS patients as compared to the healthy controls (CD34+/CD133+: 0.027 ± 0.010 % vs. 0.044 ± 0.011 %, p<0.001). EPCs depletion were significantly associated with disease duration (r=-0.52, p=0.01) and BASDAI (r=-0.45, p=0.04). Conclusion: This is the first study to demonstrate endothelial progenitor cells depletion in AS patients. EPCs depletion inversely correlates with disease duration and disease activity, suggesting the pivotal role of inflammation in depletion of EPCs. EPC would possibly also serve as a therapeutic target for preventing cardiovascular disease in AS.

Keywords: ankylosing spondylitis, endothelial progenitor cells, inflammation, vascular damage

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4002 Acupuncture in the Treatment of Parkinson's Disease-Related Fatigue: A Pilot Randomized, Controlled Study

Authors: Keng H. Kong, Louis C. Tan, Wing L. Aw, Kay Y. Tay

Abstract:

Background: Fatigue is a common problem in patients with Parkinson's disease, with reported prevalence of up to 70%. Fatigue can be disabling and has adverse effects on patients' quality of life. There is currently no satisfactory treatment of fatigue. Acupuncture is effective in the treatment of fatigue, especially that related to cancer. Its role in Parkinson's disease-related fatigue is uncertain. Aims: To evaluate the clinical efficacy of acupuncture treatment in Parkinson's disease-related fatigue. Hypothesis: We hypothesize that acupuncture is effective in alleviating Parkinson's disease-related fatigue. Design: A single center, randomized, controlled study with two parallel arms. Participants: Forty participants with idiopathic Parkinson's disease will be enrolled. Interventions: Participants will be randomized to receive verum (real) acupuncture or placebo acupuncture. The retractable non-invasive sham needle will be used in the placebo group. The intervention will be administered twice a week for five weeks. Main outcome measures: The primary outcome will be the change in general fatigue score of the multidimensional fatigue inventory at week 5. Secondary outcome measures include other subscales of the multidimensional fatigue inventory, movement disorders society-unified Parkinson's disease rating scale, Parkinson's disease questionnaire-39 and geriatric depression scale. All outcome measures will be assessed at baseline (week 0), completion of intervention (week 5) and 4 weeks after completion of intervention (week 9). Results: To date, 23 participants have been recruited and nine have completed the study. The mean age is 63.5±14.2 years, mean duration of Parkinson’s disease is 6.4±1.8 years and mean MDS-UPDRS score is 8.3±2.8. The mean general fatigue score of the multidimensional fatigue inventory is 13.5±4.6. No significant adverse event related to acupuncture is noted. Potential significance: If the results are as expected, this study will provide preliminary scientific evidence for the efficacy of acupuncture in Parkinson's Disease-related fatigue, and opens the door for a larger multicentre trial to be performed. In the longer term, it may lead to the integration of acupuncture in the care of patients with Parkinson's disease.

Keywords: acupuncture, fatigue, Parkinson's disease, trial

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4001 Role of HLA Typing in Celiac Disease

Authors: Meriche Hacene

Abstract:

Introduction: Celiac disease (CD) is a chronic immune-mediated enteropathy triggered by gluten found in wheat or oats or rye. Celiac disease is associated with the HLA-DQ2 and HLA-DQ8 susceptibility alleles. This association with the HLA DQ2/DQ8 molecules confirmed the responsibility of genetic factors that intervene in the triggering of the autoimmune process of this condition. Objective: To evaluate the results of HLA DQ2 and HLA DQ8 typing of 40 patients suspected of having CD by PCR-SSP (Polymerase Chain Reaction Sequence Specific Primers). Material and method : 40 patients suspected of celiac disease with IgA transglutaminase serology (-) and duodenal biopsy (+). HLADR/DQ PCR-SSP (fluogen-innotrain) typing was carried out. Results : The average age of adults was 40 years, children: 4 years, the sex ratio was 1M/3F. In our patients the HLA DQ2 allele is found with a frequency of 75%, the DQ8 with a frequency of 25%, 17.5% were HLA-DQ2 homozygous and 15% were HLADQ2/HLADQ8. In our series, HLADQ2, DQ8 are found in almost all patients with a frequency of 95%. 30% of patients in our study had associated positivity of HLA-DRB3, DRB4 or DRB5 alleles. Conclusion : A high prevalence of positivity of HLADQ2 alleles at the expense of HLA DQ8 was found, which is consistent with literature data. These molecules constitute an additional marker for screening and diagnosis of CD.

Keywords: HLA typing, coeliac disease, HLA DQ 2, HLA DQ8

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4000 Disease Level Assessment in Wheat Plots Using a Residual Deep Learning Algorithm

Authors: Felipe A. Guth, Shane Ward, Kevin McDonnell

Abstract:

The assessment of disease levels in crop fields is an important and time-consuming task that generally relies on expert knowledge of trained individuals. Image classification in agriculture problems historically has been based on classical machine learning strategies that make use of hand-engineered features in the top of a classification algorithm. This approach tends to not produce results with high accuracy and generalization to the classes classified by the system when the nature of the elements has a significant variability. The advent of deep convolutional neural networks has revolutionized the field of machine learning, especially in computer vision tasks. These networks have great resourcefulness of learning and have been applied successfully to image classification and object detection tasks in the last years. The objective of this work was to propose a new method based on deep learning convolutional neural networks towards the task of disease level monitoring. Common RGB images of winter wheat were obtained during a growing season. Five categories of disease levels presence were produced, in collaboration with agronomists, for the algorithm classification. Disease level tasks performed by experts provided ground truth data for the disease score of the same winter wheat plots were RGB images were acquired. The system had an overall accuracy of 84% on the discrimination of the disease level classes.

Keywords: crop disease assessment, deep learning, precision agriculture, residual neural networks

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3999 MR Enterography Findings in Pediatric and Adult Patients with Crohn's Disease

Authors: Karolina Siejka, Monika Piekarska, Monika Zbroja, Weronika Cyranka, Maryla Kuczynska, Magdalena Grzegorczyk, Malgorzata Nowakowska, Agnieszka Brodzisz, Magdalena Maria Wozniak

Abstract:

Crohn’s disease is one of chronic inflammatory bowel diseases. It is increasing in prevalence worldwide, especially with young people. The disease usually occurs in the second to the fourth decade of life. Traditionally is diagnosed by clinical indicates, endoscopic, and histological findings. Magnetic Resonance Enterography (MRE) can demonstrate mural and extramural inflammatory signs and complications, which make it a valuable diagnostic modality. The study included 76 adults and 36 children diagnosed with Crohn’s disease. Each patient underwent MRE with intravenous administration of a contrast agent. All the studies were performed using Siemens Aera 1.5T scanner according to a local study protocol. Whenever applicable, MR Enterography findings were verified with endoscopy. Forty adults and all 36 children had an active phase of Crohn’s disease; five adults had a chronic phase of the disease; one adult had both chronic and active inflammatory features. Thirty adults have no sings of pathology. In both adult and pediatric groups the most commonly observed manifestation of active disease was thickened edematous ileum wall (26 adults and 36 children). Adults had Bauhin’s valve edema in 58% cases (n=23) and mesenteric changes in 34% cases (n=9). To compare, 32 children had Bauhin’s valve edema (89%) and, in 23 cases, was found inflammatory infiltration of the peri-intestinal fat (64%). The involvement of the large intestine was more common among children (100%). Complications of Crohn’s disease were found commonly in adults (40% of adults, 22% of children). There were observed 18 fistulas (14 adults, four children) and six abscesses (2 adults, four children). MRE is a reliable method in the evaluation of Crohn’s disease activity, especially of its complications. The lack of radiations makes MRE well-tolerated modality, which can be often repeated, particularly in young patients. The disease had different medical sings depending on age – children often had a more active inflammatory process, but there were more complications in the adult group.

Keywords: Crohn's disease, diagnostics, inflammatory bowel disease, magnetic resonance enterography, MRE

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3998 Numerical and Sensitivity Analysis of Modeling the Newcastle Disease Dynamics

Authors: Nurudeen Oluwasola Lasisi

Abstract:

Newcastle disease is a highly contagious disease of birds caused by a para-myxo virus. In this paper, we presented Novel quarantine-adjusted incident and linear incident of Newcastle disease model equations. We considered the dynamics of transmission and control of Newcastle disease. The existence and uniqueness of the solutions were obtained. The existence of disease-free points was shown, and the model threshold parameter was examined using the next-generation operator method. The sensitivity analysis was carried out in order to identify the most sensitive parameters of the disease transmission. This revealed that as parameters β,ω, and ᴧ increase while keeping other parameters constant, the effective reproduction number R_ev increases. This implies that the parameters increase the endemicity of the infection of individuals. More so, when the parameters μ,ε,γ,δ_1, and α increase, while keeping other parameters constant, the effective reproduction number R_ev decreases. This implies the parameters decrease the endemicity of the infection as they have negative indices. Analytical results were numerically verified by the Differential Transformation Method (DTM) and quantitative views of the model equations were showcased. We established that as contact rate (β) increases, the effective reproduction number R_ev increases, as the effectiveness of drug usage increases, the R_ev decreases and as the quarantined individual decreases, the R_ev decreases. The results of the simulations showed that the infected individual increases when the susceptible person approaches zero, also the vaccination individual increases when the infected individual decreases and simultaneously increases the recovery individual.

Keywords: disease-free equilibrium, effective reproduction number, endemicity, Newcastle disease model, numerical, Sensitivity analysis

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3997 Antimicrobial and Anti-Biofilm Activity of Non-Thermal Plasma

Authors: Jan Masak, Eva Kvasnickova, Vladimir Scholtz, Olga Matatkova, Marketa Valkova, Alena Cejkova

Abstract:

Microbial colonization of medical instruments, catheters, implants, etc. is a serious problem in the spread of nosocomial infections. Biofilms exhibit enormous resistance to environment. The resistance of biofilm populations to antibiotic or biocides often increases by two to three orders of magnitude in comparison with suspension populations. Subjects of interests are substances or physical processes that primarily cause the destruction of biofilm, while the released cells can be killed by existing antibiotics. In addition, agents that do not have a strong lethal effect do not cause such a significant selection pressure to further enhance resistance. Non-thermal plasma (NTP) is defined as neutral, ionized gas composed of particles (photons, electrons, positive and negative ions, free radicals and excited or non-excited molecules) which are in permanent interaction. In this work, the effect of NTP generated by the cometary corona with a metallic grid on the formation and stability of biofilm and metabolic activity of cells in biofilm was studied. NTP was applied on biofilm populations of Staphylococcus epidermidis DBM 3179, Pseudomonas aeruginosa DBM 3081, DBM 3777, ATCC 15442 and ATCC 10145, Escherichia coli DBM 3125 and Candida albicans DBM 2164 grown on solid media on Petri dishes and on the titanium alloy (Ti6Al4V) surface used for the production joint replacements. Erythromycin (for S. epidermidis), polymyxin B (for E. coli and P. aeruginosa), amphotericin B (for C. albicans) and ceftazidime (for P. aeruginosa) were used to study the combined effect of NTP and antibiotics. Biofilms were quantified by crystal violet assay. Metabolic activity of the cells in biofilm was measured using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) colorimetric test based on the reduction of MTT into formazan by the dehydrogenase system of living cells. Fluorescence microscopy was applied to visualize the biofilm on the surface of the titanium alloy; SYTO 13 was used as a fluorescence probe to stain cells in the biofilm. It has been shown that biofilm populations of all studied microorganisms are very sensitive to the type of used NTP. The inhibition zone of biofilm recorded after 60 minutes exposure to NTP exceeded 20 cm², except P. aeruginosa DBM 3777 and ATCC 10145, where it was about 9 cm². Also metabolic activity of cells in biofilm differed for individual microbial strains. High sensitivity to NTP was observed in S. epidermidis, in which the metabolic activity of biofilm decreased after 30 minutes of NTP exposure to 15% and after 60 minutes to 1%. Conversely, the metabolic activity of cells of C. albicans decreased to 53% after 30 minutes of NTP exposure. Nevertheless, this result can be considered very good. Suitable combinations of exposure time of NTP and the concentration of antibiotic achieved in most cases a remarkable synergic effect on the reduction of the metabolic activity of the cells of the biofilm. For example, in the case of P. aeruginosa DBM 3777, a combination of 30 minutes of NTP with 1 mg/l of ceftazidime resulted in a decrease metabolic activity below 4%.

Keywords: anti-biofilm activity, antibiotic, non-thermal plasma, opportunistic pathogens

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3996 Features Reduction Using Bat Algorithm for Identification and Recognition of Parkinson Disease

Authors: P. Shrivastava, A. Shukla, K. Verma, S. Rungta

Abstract:

Parkinson's disease is a chronic neurological disorder that directly affects human gait. It leads to slowness of movement, causes muscle rigidity and tremors. Gait serve as a primary outcome measure for studies aiming at early recognition of disease. Using gait techniques, this paper implements efficient binary bat algorithm for an early detection of Parkinson's disease by selecting optimal features required for classification of affected patients from others. The data of 166 people, both fit and affected is collected and optimal feature selection is done using PSO and Bat algorithm. The reduced dataset is then classified using neural network. The experiments indicate that binary bat algorithm outperforms traditional PSO and genetic algorithm and gives a fairly good recognition rate even with the reduced dataset.

Keywords: parkinson, gait, feature selection, bat algorithm

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3995 DNAJB6 Chaperone Prevents the Aggregation of Intracellular but not Extracellular Aβ Peptides Associated with Alzheimer’s Disease

Authors: Rasha M. Hussein, Reem M. Hashem, Laila A. Rashed

Abstract:

Alzheimer’s disease is the most common dementia disease in the elderly. It is characterized by the accumulation of extracellular amyloid β (Aβ) peptides and intracellular hyper-phosphorylated tau protein. In addition, recent evidence indicates that accumulation of intracellular amyloid β peptides may play a role in Alzheimer’s disease pathogenesis. This suggests that intracellular Heat Shock Proteins (HSP) that maintain the protein quality control in the cell might be potential candidates for disease amelioration. DNAJB6, a member of DNAJ family of HSP, effectively prevented the aggregation of poly glutamines stretches associated with Huntington’s disease both in vitro and in cells. In addition, DNAJB6 was found recently to delay the aggregation of Aβ42 peptides in vitro. In the present study, we investigated the ability of DNAJB6 to prevent the aggregation of both intracellular and extracellular Aβ peptides using transfection of HEK293 cells with Aβ-GFP and recombinant Aβ42 peptides respectively. We performed western blotting and immunofluorescence techniques. We found that DNAJB6 can prevent Aβ-GFP aggregation, but not the seeded aggregation initiated by extracellular Aβ peptides. Moreover, DNAJB6 required interaction with HSP70 to prevent the aggregation of Aβ-GFP protein and its J-domain was essential for this anti-aggregation activity. Interestingly, overexpression of other DNAJ proteins as well as HSPB1 suppressed Aβ-GFP aggregation efficiently. Our findings suggest that DNAJB6 is a promising candidate for the inhibition of Aβ-GFP mediated aggregation through a canonical HSP70 dependent mechanism.

Keywords: , Alzheimer’s disease, chaperone, DNAJB6, aggregation

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3994 Neural Network Based Decision Trees Using Machine Learning for Alzheimer's Diagnosis

Authors: P. S. Jagadeesh Kumar, Tracy Lin Huan, S. Meenakshi Sundaram

Abstract:

Alzheimer’s disease is one of the prevalent kind of ailment, expected for impudent reconciliation or an effectual therapy is to be accredited hitherto. Probable detonation of patients in the upcoming years, and consequently an enormous deal of apprehension in early discovery of the disorder, this will conceivably chaperon to enhanced healing outcomes. Complex impetuosity of the brain is an observant symbolic of the disease and a unique recognition of genetic sign of the disease. Machine learning alongside deep learning and decision tree reinforces the aptitude to absorb characteristics from multi-dimensional data’s and thus simplifies automatic classification of Alzheimer’s disease. Susceptible testing was prophesied and realized in training the prospect of Alzheimer’s disease classification built on machine learning advances. It was shrewd that the decision trees trained with deep neural network fashioned the excellent results parallel to related pattern classification.

Keywords: Alzheimer's diagnosis, decision trees, deep neural network, machine learning, pattern classification

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3993 A Preliminary Outcome of the Effect of an Accumulating 10,000 Daily Steps on Blood Pressure and Diabetes in Overweight Thai Participants

Authors: Kornanong Yuenyongchaiwat, Duangnate Pepatsitipong, Panthip Sangprasert

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High blood pressure and diabetes have been suggested as being non-communicable disease (NCDs), and there is one of the components of the definition of metabolic syndrome. Therefore, the purpose of this study was to evaluate the effect of a 12-week pedometer based community walking intervention on change in resting blood pressure and blood glucose in participants with overweight in the community setting. Method: Participants were recruited both males and females who had a sedentary lifestyle aged 35-59 years (mean aged 49.67 years). A longitudinal quasi-experimental study was designed with 35 overweight participants who had body mass index ≥ 25 kg/m2. These volunteers were assigned to the 12-week pedometer-based walking program (an accumulated at least 10,000 steps a day). Blood pressure and blood glucose were measured initially before and after 12-week intervention. Results: Systolic blood pressure and heart rate were significantly lower in 30 individuals who had accumulated 10,000 steps d-1 in the intervention group at 12 week follow-up (-13.74 mmHg and 5.3 bpm, respectively). In addition, reduction in blood glucose (-14.89 mmol) in the intervention participants was statistically significant (p < .001). A regression analysis indicated that reductions in systolic blood pressure were significantly related to the increase in steps per day. Conclusion: The accumulation of least 10,000 steps d-1 resulted in decreased resting systolic blood pressure and blood glucose in overweight participants. This has also shown that an increase in physical activity in overweight participants with sedentary lifestyle by accumulating at least 10,000 steps a day can reduce the risk of cardiovascular disease (e.g., hypertension and diabetes).

Keywords: blood glucose, blood pressure, diabetes, hypertension, physical activity, walking

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3992 Geographic Information System Using Google Fusion Table Technology for the Delivery of Disease Data Information

Authors: I. Nyoman Mahayasa Adiputra

Abstract:

Data in the field of health can be useful for the purposes of data analysis, one example of health data is disease data. Disease data is usually in a geographical plot in accordance with the area. Where the data was collected, in the city of Denpasar, Bali. Disease data report is still published in tabular form, disease information has not been mapped in GIS form. In this research, disease information in Denpasar city will be digitized in the form of a geographic information system with the smallest administrative area in the form of district. Denpasar City consists of 4 districts of North Denpasar, East Denpasar, West Denpasar and South Denpasar. In this research, we use Google fusion table technology for map digitization process, where this technology can facilitate from the administrator and from the recipient information. From the administrator side of the input disease, data can be done easily and quickly. From the receiving end of the information, the resulting GIS application can be published in a website-based application so that it can be accessed anywhere and anytime. In general, the results obtained in this study, divided into two, namely: (1) Geolocation of Denpasar and all of Denpasar districts, the process of digitizing the map of Denpasar city produces a polygon geolocation of each - district of Denpasar city. These results can be utilized in subsequent GIS studies if you want to use the same administrative area. (2) Dengue fever mapping in 2014 and 2015. Disease data used in this study is dengue fever case data taken in 2014 and 2015. Data taken from the profile report Denpasar Health Department 2015 and 2016. This mapping can be useful for the analysis of the spread of dengue hemorrhagic fever in the city of Denpasar.

Keywords: geographic information system, Google fusion table technology, delivery of disease data information, Denpasar city

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3991 Phylogenetic Analysis of the Myxosporea Detected from Emaciated Olive Flounder (Paralichthys olivaceus) in Korea

Authors: Seung Min Kim, Lyu Jin Jun, Joon Bum Jeong

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The Myxosporea to cause emaciation disease in the olive flounder (Paralichthys olivaceus) is a pathogen to cause severe losses in the aquafarming industry in Korea. The 3,362 bp of DNA nucleotide sequences of four myxosporean strains (EM-HM-12, EM-MA-13, EM-JJ-14, and EM-MS-15) detected by PCR method from olive flounder suffering from emaciation disease in Korea during 2012-2015 were sequenced and deposited in GenBank database (GenBank accession numbers: KU377574, KT321705, KU377575 and KU377573, respectively). The homologies of DNA nucleotide sequences of four strains were compared to each other and were more than 99.7% homologous between the four strains. All of the strains were identified as Parvicapsula petunia based on the results of phylogenetic analysis. The results in this study would be useful for the research of emaciation disease in olive flounder of Korea.

Keywords: disease, emaciation, olive flounder, phylogenetic analysis

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3990 A New Index for the Differential Diagnosis of Morbid Obese Children with and without Metabolic Syndrome

Authors: Mustafa M. Donma, Orkide Donma

Abstract:

Metabolic syndrome (MetS) is a severe health problem which is common among obese individuals. The components of MetS are rather stable in adults compared to the components discussed for children. Due to the ambiguity in this group of the population, how to diagnose MetS in morbid obese (MO) children still constitutes a matter of discussion. For this purpose, a formula, which facilitates the diagnosis of MetS in MO children, was investigated. The aim of this study was to develop a formula which was capable of discriminating MO children with and without MetS findings. Study population comprised MO children. Age and sex-dependent body mass index (BMI) percentiles of the children were above 99. Metabolic syndrome components were also determined. Elevated systolic and diastolic blood pressures (SBP and DBP), elevated fasting blood glucose (FBG), elevated triglycerides (TRG), and/or depressed high density lipoprotein cholesterol (HDL-C) in addition to central obesity were listed as MetS components for each child. Presence of at least two of these components confirmed that the case was MetS. Two groups were constituted. In the first group, there were forty-two MO children without MetS components. Second group was composed of forty-four MO children with at least two MetS components. Anthropometric measurements, including weight, height, waist, and hip circumferences, were performed following physical examination. Body mass index and homeostatic model assessment of insulin resistance values were calculated. Informed consent forms were obtained from the parents of the children. Institutional Non-Interventional Ethics Committee approved the study design. Blood pressure values were recorded. Routine biochemical analysis, including FBG, insulin (INS), TRG, HDL-C were performed. The performance and the clinical utility of the Diagnostic Obesity Notation Model Assessment Metabolic Syndrome Index (DONMA MetS index) [(INS/FBG)/(HDL-C/TRG)*100] was tested. Appropriate statistical tests were applied to the study data. p value smaller than 0.05 was defined as significant. Metabolic syndrome index values were 41.6±5.1 in MO group and 104.4±12.8 in MetS group. Corresponding values for HDL-C values were 54.5±13.2 mg/dl and 44.2±11.5 mg/dl. There were statistically significant differences between the groups (p<0.001). Upon evaluation of the correlations between MetS index and HDL-C values, a much stronger negative correlation was found in MetS group (r=-0.515; p=0.001) in comparison with the correlation detected in MO group (r=-0.371; p=0.016). From these findings, it was concluded that the statistical significance degree of the difference between MO and MetS groups was highly acceptable for this recently introduced MetS index as expected. This was due to the involvement of all of the biochemically defined MetS components into the index. This is particularly important because each of these four parameters used in the formula is cardiac risk factor. Aside from discriminating MO children with and without MetS findings, MetS index introduced in this study is important from the cardiovascular risk point of view in MetS group of children.

Keywords: children, fasting blood glucose, high density lipoprotein cholesterol, index, insulin, metabolic syndrome, morbid obesity, triglycerides.

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3989 The Effects of Health Education Programme on Knowledge and Prevention of Cerebrovascular Disease among Hypertensive Patients in University College Hospital, Ibadan

Authors: T. A. Ajiboye

Abstract:

This study examines the effects of health education programme on knowledge and prevention of cerebrovascular disease among hypertensive patients in University College Hospital, Ibadan. A quasi-experimental design was adopted for the study. 100 hypertensive patients were conveniently selected from general outpatient department in UCH. Data generated were analyzed using ANOVA at 0.05 alpha levels. The findings of the study revealed that health education programme significantly influenced both the knowledge of hypertensive patients (F=22.70; DF=1/99; p < .05) and their attitude (F=10.377; DF=1/99; p < .05) on cerebrovascular disease. Findings also discovered that health education programme significantly reduce the complication of hypertension to cerebrovascular disease (F= 16.41; DF=7/286; p < 0.05) among the hypertensive patients at UCH. Based on the findings, it is recommended that hypertensive patients should relieve themselves from stress, engage themselves on regular exercises, compliance with drug and diet regimes coupled with keeping up of regular appointment. Government should design health information that will center on hypertension and cerebrovascular disease so as to keep health and community development problems to the barest minimum. Finally, there should be provision of social amenities and recreational centers, as this will prevents hypertension problems.

Keywords: cerebrovascular disease, effectiveness, health education, hypertension, knowledge, prevention

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3988 Parkinson's Disease and Musculoskeletal Problems

Authors: Ozge Yilmaz Kusbeci, Ipek Inci

Abstract:

Aim: Musculoskeletal problems are very common in Parkinson’s disease (PD). They affect quality of life and cause disabilities. However they are under-evaluated, and under-treated. The aim of this study is to evaluate the prevalence and clinical features of musculoskeletal problems in patients with Parkinson disease (PD) compared to controls. Methods: 50 PD patients and 50 age and sex matched controls were interviewed by physicians about their musculoskeletal problems. Results: The prevalence of musculoskeletal problems was significantly higher in the PD group than in the control group (p < 0.05). Commonly involved body sites were the shoulder, low back, and knee. The shoulder and low back was more frequently involved in the PD group than in the control group. However, the knee was similarly involved in both groups. Among the past diagnoses associated with musculoskeletal problems, frozen shoulder, low back pain and osteoporosis more common in the PD group than in the control group (p < 0.05). Furthermore, musculoskeletal problems in the PD group tended to receive less treatment than that of the control group. Conclusion: Musculoskeletal problems were more common in the PD group than in the controls. Therefore assessment and treatment of musculoskeletal problems could improve quality of life in PD patients.

Keywords: parkinson disease, musculoskeletal problems, quality of life, PD disease

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3987 Prevalence of Physical Activity Levels and Perceived Benefits of and Barriers to Physical Activity among Jordanian Patients with Coronary Heart Disease: A Cross-Sectional Study

Authors: Eman Ahmed Alsaleh

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Background: Many studies published in other countries identified certain perceived benefits and barriers to physical activity among patients with coronary heart disease. Nevertheless, there is no data about the issue relating to Jordanian patients with coronary heart disease. Objective: This study aimed to describe the prevalence of level of physical activity, benefits of and barriers to physical activity as perceived by Jordanian patients with coronary heart disease, and the relationship between physical activity and perceived benefits of and barriers to physical activity. In addition, it focused on examining the influence of selected sociodemographic and health characteristics on physical activity and the perceived benefits of and barriers to physical activity. Methods: A cross-sectional design was performed on a sample of 400 patients with coronary heart disease. They were given a list of perceived benefits and barriers to physical activity and asked to what extent they disagreed or agreed with each. Results: Jordanian patients with coronary heart disease perceived various benefits and barriers to physical activity. Most of these benefits were physiologically related (average mean = 5.7, SD = .7). The most substantial barriers to physical activity as perceived by the patients were: feeling anxiety, not having enough time, lack of interest, bad weather, and feeling of being uncomfortable. Sociodemographic and health characteristics that significantly influenced perceived barriers to physical activity were age, gender, health perception, chest pain frequency, education, job, caring responsibilities, ability to travel alone, smoking, and previous and current physical activity behaviour. Conclusion: This research demonstrates that patients with coronary heart disease have perceived physiological benefits of physical activity, and they have perceived motivational, physical health, and environmental barriers to physical activity, which is significant in developing intervention strategies that aim to maximize patients' participation in physical activity and overcome barriers to physical activity.

Keywords: prevalence, coronary heart disease, physical activity, perceived barriers

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3986 Early Diagnosis of Alzheimer's Disease Using a Combination of Images Processing and Brain Signals

Authors: E. Irankhah, M. Zarif, E. Mazrooei Rad, K. Ghandehari

Abstract:

Alzheimer's prevalence is on the rise, and the disease comes with problems like cessation of treatment, high cost of treatment, and the lack of early detection methods. The pathology of this disease causes the formation of protein deposits in the brain of patients called plaque amyloid. Generally, the diagnosis of this disease is done by performing tests such as a cerebrospinal fluid, CT scan, MRI, and spinal cord fluid testing, or mental testing tests and eye tracing tests. In this paper, we tried to use the Medial Temporal Atrophy (MTA) method and the Leave One Out (LOO) cycle to extract the statistical properties of the three Fz, Pz, and Cz channels of ERP signals for early diagnosis of this disease. In the process of CT scan images, the accuracy of the results is 81% for the healthy person and 88% for the severe patient. After the process of ERP signaling, the accuracy of the results for a healthy person in the delta band in the Cz channel is 81% and in the alpha band the Pz channel is 90%. In the results obtained from the signal processing, the results of the severe patient in the delta band of the Cz channel were 89% and in the alpha band Pz channel 92%.

Keywords: Alzheimer's disease, image and signal processing, LOO cycle, medial temporal atrophy

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3985 Hypergraph Models of Metabolism

Authors: Nicole Pearcy, Jonathan J. Crofts, Nadia Chuzhanova

Abstract:

In this paper, we employ a directed hypergraph model to investigate the extent to which environmental variability influences the set of available biochemical reactions within a living cell. Such an approach avoids the limitations of the usual complex network formalism by allowing for the multilateral relationships (i.e. connections involving more than two nodes) that naturally occur within many biological processes. More specifically, we extend the concept of network reciprocity to complex hyper-networks, thus enabling us to characterize a network in terms of the existence of mutual hyper-connections, which may be considered a proxy for metabolic network complexity. To demonstrate these ideas, we study 115 metabolic hyper-networks of bacteria, each of which can be classified into one of 6 increasingly varied habitats. In particular, we found that reciprocity increases significantly with increased environmental variability, supporting the view that organism adaptability leads to increased complexities in the resultant biochemical networks.

Keywords: complexity, hypergraphs, reciprocity, metabolism

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3984 Advanced Eales’ Disease with Neovascular Glaucoma at First Presentation: Case Report

Authors: Mohammed A. Alfayyadh, Halla A. AlAbdulhadi, Mahdi H. Almubarak

Abstract:

Purpose: Eales’ disease is an idiopathic vasculitis that affects the peripheral retina. It is characterized by recurrent vitreous hemorrhage as a complication of retinal neovascularization. It is more prevalent in India and affects young males. Here we present a patient with neovascular glaucoma as a rare first presentation of Eales’ disease. Observations: This is a 24-year-old Indian gentleman, who complained of a sudden decrease in vision in the left eye over less than 24 hours, along with frontal headache and eye pain for the last three weeks. Ocular examination revealed peripheral retinal ischemia in the right eye, very high intraocular pressure, rubeosis iridis, vitreous hemorrhage and extensive retinal ischemia in the left eye, vascular sheathing and neovascularization in both eyes. Purified protein derivative skin test was positive. The patient was managed with anti-glaucoma, intravitreal anti-vascular endothelial growth factor and laser photocoagulation. Systemic steroids and anti-tuberculous therapy were also initiated. Conclusions: Neovascular glaucoma is an infrequent complication of Eales’ disease. However, the lack of early detection of the disease in the early stages might lead to such serious complication.

Keywords: case report, Eales’ disease, mycobacterium tuberculosis, neovascular glaucoma

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3983 Blood Chemo-Profiling in Workers Exposed to Occupational Pyrethroid Pesticides to Identify Associated Diseases

Authors: O. O. Sufyani, M. E. Oraiby, S. A. Qumaiy, A. I. Alaamri, Z. M. Eisa, A. M. Hakami, M. A. Attafi, O. M. Alhassan, W. M. Elsideeg, E. M. Noureldin, Y. A. Hobani, Y. Q. Majrabi, I. A. Khardali, A. B. Maashi, A. A. Al Mane, A. H. Hakami, I. M. Alkhyat, A. A. Sahly, I. M. Attafi

Abstract:

According to the Food and Agriculture Organization (FAO) Pesticides Use Database, pesticide use in agriculture in Saudi Arabia has more than doubled from 4539 tons in 2009 to 10496 tons in 2019. Among pesticides, pyrethroids is commonly used in Saudi Arabia. Pesticides may increase susceptibility to a variety of diseases, particularly among pesticide workers, due to their extensive use, indiscriminate use, and long-term exposure. Therefore, analyzing blood chemo-profiles and evaluating the detected substances as biomarkers for pyrethroid pesticide exposure may assist to identify and predicting adverse effects of exposure, which may be used for both preventative and risk assessment purposes. The purpose of this study was to (a) analyze chemo-profiling by Gas Chromatography-Mass Spectrometry (GC-MS) analysis, (b) identify the most commonly detected chemicals in a time-exposure-dependent manner using a Venn diagram, and (c) identify their associated disease among pesticide workers using analyzer tools on the Comparative Toxicogenomics Database (CTD) website, (250 healthy male volunteers (20-60 years old) who deal with pesticides in the Jazan region of Saudi Arabia (exposure intervals: 1-2, 4-6, 6-8, more than 8 years) were included in the study. A questionnaire was used to collect demographic information, the duration of pesticide exposure, and the existence of chronic conditions. Blood samples were collected for biochemistry analysis and extracted by solid-phase extraction for gas chromatography-mass spectrometry (GC-MS) analysis. Biochemistry analysis reveals no significant changes in response to the exposure period; however, an inverse association between the albumin level and the exposure interval was observed. The blood chemo-profiling was differentially expressed in an exposure time-dependent manner. This analysis identified the common chemical set associated with each group and their associated significant occupational diseases. While some of these chemicals are associated with a variety of diseases, the distinguishing feature of these chemically associated disorders is their applicability for prevention measures. The most interesting finding was the identification of several chemicals; erucic acid, pelargonic acid, alpha-linolenic acid, dibutyl phthalate, diisobutyl phthalate, dodecanol, myristic Acid, pyrene, and 8,11,14-eicosatrienoic acid, associated with pneumoconiosis, asbestosis, asthma, silicosis and berylliosis. Chemical-disease association study also found that cancer, digestive system disease, nervous system disease, and metabolic disease were the most often recognized disease categories in the common chemical set. The hierarchical clustering approach was used to compare the expression patterns and exposure intervals of the chemicals found commonly. More study is needed to validate these chemicals as early markers of pyrethroid insecticide-related occupational disease, which might assist evaluate and reducing risk. The current study contributes valuable data and recommendations to public health.

Keywords: occupational, toxicology, chemo-profiling, pesticide, pyrethroid, GC-MS

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3982 Searching for Health-Related Information on the Internet: A Case Study on Young Adults

Authors: Dana Weimann Saks

Abstract:

This study aimed to examine the use of the internet as a source of health-related information (HRI), as well as the change in attitudes following the online search for HRI. The current study sample included 88 participants, randomly divided into two experimental groups. One was given the name of an unfamiliar disease and told to search for information about it using various search engines, and the second was given a text about the disease from a credible scientific source. The study findings show a large percentage of participants used the internet as a source of HRI. Likewise, no differences were found in the extent to which the internet was used as a source of HRI when demographics were compared. Those who searched for the HRI on the internet had more negative opinions and believed symptoms of the disease were worse than the average opinion among those who obtained the information about the disease from a credible scientific source. The Internet clearly influences the participants’ beliefs, regardless of demographic differences.

Keywords: health-related information, internet, young adults, HRI

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3981 The Relationship of Aromatase Activity and Being Very Overweight in East Indian Women with or Without Polycystic Ovary Disease

Authors: Dipanshu Sur, Ratnabali Chakravorty, Rimi Pal, Siddhartha Chatterjee, Joyshree Chaterjee, Amal Mallik

Abstract:

Background: Women with polycystic ovary disease (PCOD) frequently suffer from metabolic disturbances. PCOD is a common ovulatory disorder in young women, which affects 5-10% of the population and results in infertility due to anovulation. Importantly, aromatase in ovarian granulosa and luteinized granulosa cells plays an important role for women of reproductive age. Generation and metabolism of androgen is directly related to aromatase activity. The E2/T ratio provides important information about aromatase activity because conversion of androgens to estrogens is mediated by CYP19, suggesting that the E2/T ratio may be a direct marker of aromatase activity. The nature of the interaction between ovarian aromatase activity and PCOD in women has been controversial, and the impact of weight gain on aromatase activity as well as E2 levels is unknown. Aim: The objective of this study was to investigate the association and relation between aromatase activity and levels of body mass index (BMI) from a reproductive hormone perspective in a group of women with or without PCOD. Methods: We designed a cohort study which included 200 individuals. It enrolled 100 cases of PCOD based on 2006 Rotterdam criteria and 100 ovulatory normal- non PCOD, healthy, age-matched controls. Plasma sex hormones viz. estradiol (E2), testosterone (T), follicle stimulating hormone (FSH), and luteinizing hormone (LH) were measured by ELISA on the second day of the menstrual cycle, together with BMI and E2/T were calculated. Aromatase activity in PCOD patients with different BMI, T and E2 levels were compared. Results: PCOD patients showed significantly increased levels of BMI, E2 (P=0.004), T and LH, while their E2/T (P= <0.001), FSH and FSH/LH values were decreased compared with the control group. Higher E2 levels correlated with a relatively enhanced E2/T as well as T and LH levels but reduced BMI, FSH and FSH/LH levels in women with PCOD. Hyperandrogenic PCOD patients had increased E2 levels but their aromatase activity was markedly inhibited independent of their BMI values. Conclusions: We found a significant decrease of ovarian aromatase activity in women with PCOD as compared to controls. Our study showed that ovarian aromatase activity in PCOD was decreased which was independent of BMI. Enhancing aromatase activity may become an optimized strategy for developing therapies for PCOD women, especially those with obesity.

Keywords: aromatase activity, polycystic ovary disease, obesity, body mass index

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3980 Modification of the Risk for Incident Cancer with Changes in the Metabolic Syndrome Status: A Prospective Cohort Study in Taiwan

Authors: Yung-Feng Yen, Yun-Ju Lai

Abstract:

Background: Metabolic syndrome (MetS) is reversible; however, the effect of changes in MetS status on the risk of incident cancer has not been extensively studied. We aimed to investigate the effects of changes in MetS status on incident cancer risk. Methods: This prospective, longitudinal study used data from Taiwan’s MJ cohort of 157,915 adults recruited from 2002–2016 who had repeated MetS measurements 5.2 (±3.5) years apart and were followed up for the new onset of cancer over 8.2 (±4.5) years. A new diagnosis of incident cancer in study individuals was confirmed by their pathohistological reports. The participants’ MetS status included MetS-free (n=119,331), MetS-developed (n=14,272), MetS-recovered (n=7,914), and MetS-persistent (n=16,398). We used the Fine-Gray sub-distribution method, with death as the competing risk, to determine the association between MetS changes and the risk of incident cancer. Results: During the follow-up period, 7,486 individuals had new development of cancer. Compared with the MetS-free group, MetS-persistent individuals had a significantly higher risk of incident cancer (adjusted hazard ratio [aHR], 1.10; 95% confidence interval [CI], 1.03-1.18). Considering the effect of dynamic changes in MetS status on the risk of specific cancer types, MetS persistence was significantly associated with a higher risk of incident colon and rectum, kidney, pancreas, uterus, and thyroid cancer. The risk of kidney, uterus, and thyroid cancer in MetS-recovered individuals was higher than in those who remained MetS but lower than MetS-persistent individuals. Conclusions: Persistent MetS is associated with a higher risk of incident cancer, and recovery from MetS may reduce the risk. The findings of our study suggest that it is imperative for individuals with pre-existing MetS to seek treatment for this condition to reduce the cancer risk.

Keywords: metabolic syndrome change, cancer, risk factor, cohort study

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3979 Effect Of Selected Food And Nutrition Environments On Prevalence Of Cardio-Metabolic Risk Factors With Emphasis On Worksite Environment In Urban Delhi

Authors: Deepa Shokeen, Bani Tamber Aeri

Abstract:

Food choice is a complex process influenced by the interplay of multiple factors, including physical, socio-cultural and economic factors comprising macro or micro level food environments. While a clear understanding of the relationship between what we eat and the environmental context in which these food choices are made is still needed; it has however now been shown that food environments do play a significant role in the obesity epidemic and increasing cardio-metabolic risk factors. Evidence in other countries indicates that the food environment may strongly influence the prevalence of obesity and cardio-metabolic risk factors among young adults. Although in the Indian context, data does indicate the associations between sedentary lifestyle, stress, faulty diets but very little evidence supports the role of food environment in influencing cardio-metabolic health among employed adults. Thus, this research is required to establish how different environments affect different individuals as individuals interact with the environment on a number of levels. Methodology: The objective of the present study is to assess the effect of selected food and nutrition environments with emphasis on worksite environment and to analyse its impact on the food choices and dietary behaviour of the employees (25-45 years of age) of the organizations under study. In the proposed study an attempt will be made to randomly select various worksite environments from Delhi and NCR. The study will be conducted in two phases. In phase I, Information will be obtained on their socio-demographic profile and various factors influencing their food choices including most commonly consumed foods and most frequently visited eating outlets in and around the work place. Data will also be gathered on anthropometry (height, weight, waist circumference), biochemical parameters (lipid profile and fasting glucose), blood pressure and dietary intake. Based on the findings of phase I, a list of the most frequently visited eating outlets in and around the workplace will be prepared in Phase II. These outlets will then be subjected to nutrition environment assessment survey (NEMS). On the basis of the information gathered from phase I and phase II, influence of selected food and nutrition environments on food choice, dietary behaviour and prevalence of cardio-metabolic risk factors among employed adults will be assessed. Expected outcomes: The proposed study will try to ascertain the impact of selected food and nutrition environments on food choice and dietary intake of the working adults as it is important to learn how these food environments influence the eating perceptions and health behavior of the adults. In addition to this, anthropometry blood pressure and biochemical assessment of the subjects will be done to assess the prevalence of cardio-metabolic risk factors. If the findings indicate that the work environment, where most of these young adults spend their productive hours of the day, influence their health, than perhaps steps maybe needed to make these environments more conducive to health.

Keywords: food and nutrition environment, cardio-metabolic risk factors, India, worksite environment

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3978 The out of Proportion - Pulmonary Hypertension in Indians with Chronic Lung Disease

Authors: S. P. Chintan, A. M. Khoja, M. Modi, R. K. Chopra, S. Garde, D. Jain, O. Kajale

Abstract:

Pulmonary Hypertension is a rare but debilitating disease that affects individuals of all ages and walks of life. As recent as 15 years ago, a patient diagnosed with PH was given an average survival rate of 2.8 years. Recent advances in treatment options have allowed patients to improve quality o and quantity of life. Initial screening for PH is through echocardiography with final diagnosis confirmed through right heart catheterization. PH is now considered to have five major classifications with subgroups among each. The mild to moderate PH is common in chronic lung diseases like Chronic obstructive pulmonary diseases and Interstitial lung disease. But very severe PH is noted in few cases. In COPD patients, PH is associated with an increased risk of severe exacerbations and a reduced life expectancy. Similarly, in patients with ILD, the presence of PH correlates with a poor prognosis. Early diagnosis is essential to slow disease progression. We report here five cases of severe PH (Out of Proportion) of which four cases were of COPD and another one of IPF (UIP pattern). There echocardiography showed gross RA/RV dilatation, interventricular septum bulging to the left and mPAP of more than 100 mmHg in all the five cases. These patients were put on LTOT, pulmonary rehabilitation, combination pharmacotherapy of vasodilators and diuretics in continuation to the treatment of underlying disease. As these patients have grave prognosis close monitoring and follow up is required. Physicians associated with respiratory care and treating chronic lung disease should have knowledge in the diagnosis and management of patients with PH.

Keywords: COPD, pulmonary hypertension, chronic lung disease, India

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3977 Unpleasant Symptom Clusters Influencing Quality of Life among Patients with Chronic Kidney Disease

Authors: Anucha Taiwong, Nirobol Kanogsunthornrat

Abstract:

This predictive research aimed to investigate the symptom clusters that influence the quality of life among patients with chronic kidney disease, as indicated in the Theory of Unpleasant Symptoms. The purposive sample consisted of 150 patients with stage 3-4 chronic kidney disease who received care at an outpatient chronic kidney disease clinic of a tertiary hospital in Roi-Et province. Data were collected from January to March 2016 by using a patient general information form, unpleasant symptom form, and quality of life (SF-36) and were analyzed by using descriptive statistics, factor analysis, and multiple regression analysis. Findings revealed six core symptom clusters including symptom cluster of the mental and emotional conditions, peripheral nerves abnormality, fatigue, gastro-intestinal tract, pain and, waste congestion. Significant predictors for quality of life were the two symptom clusters of pain (Beta = -.220; p < .05) and the mental and emotional conditions (Beta=-.204; p<.05) which had predictive value of 19.10% (R2=.191, p<.05). This study indicated that the symptom cluster of pain and the mental and emotional conditions would worsen the patients’ quality of life. Nurses should be attentive in managing the two symptom clusters to facilitate the quality of life among patients with chronic kidney disease.

Keywords: chronic kidney disease, symptom clusters, predictors of quality of life, pre-dialysis

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3976 Targeting Methionine Metabolism In Gastric Cancer; Promising To Improve Chemosensetivity With Non-hetrogeneity

Authors: Nigatu Tadesse, Li Juan, Liuhong Ming

Abstract:

Gastric cancer (GC) is the fifth most common and fourth deadly cancer in the world with limited treatment options at late advanced stage in which surgical therapy is not recommended with chemotherapy remain as the mainstay of treatment. However, the occurrence of chemoresistance as well as intera-tumoral and inter-tumoral heterogeneity of response to targeted and immunotherapy underlined a clear unmet treatment need in gastroenterology. Several molecular and cellular alterations ascribed for chemo resistance in GC including cancer stem cells (CSC) and tumor microenvironment (TME) remodeling. Cancer cells including CSC bears higher metabolic demand and major changes in TME involves alterations of gut microbiota interacting with nutrients metabolism. Metabolic upregulation in lipids, carbohydrates, amino acids, fatty acids biosynthesis pathways identified as a common hall mark in GC. Metabolic addiction to methionine metabolism occurs in many cancer cells to promote the biosynthesis of S-Adenosylmethionine (SAM), a universal methyl donor molecule for high rate of transmethylation in GC and promote cell proliferation. Targeting methionine metabolism found to promotes chemo-sensitivity with treatment non-heterogeneity. Methionine restriction (MR) promoted the arrest of cell cycle at S/G2 phase and enhanced downregulation of GC cells resistance to apoptosis (including ferroptosis), which suggests the potential of synergy with chemotherapies acting at S-phase of the cell cycle as well as inducing cell apoptosis. Accumulated evidences showed both the biogenesis as well as intracellular metabolism of exogenous methionine could be safe and effective target for therapy either alone or in combination with chemotherapies. This review article provides an over view of the upregulation in methionine biosynthesis pathway and the molecular signaling through the PI3K/Akt/mTOR-c-MYC axis to promote metabolic reprograming through activating the expression of L-type aminoacid-1 (LAT1) transporter and overexpression of Methionine adenosyltransferase 2A(MAT2A) for intercellular metabolic conversion of exogenous methionine to SAM in GC, and the potential of targeting with novel therapeutic agents such as methioninase (METase), Methionine adenosyltransferase 2A (MAT2A), c-MYC, methyl like transferase 16 (METTL16) inhibitors that are currently under clinical trial development stages and future perspectives.

Keywords: gastric cancer, methionine metabolism, pi3k/akt/mtorc1-c-myc axis, gut microbiota, MAT2A, c-MYC, METTL16, methioninase

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