Qatar Foundation Annual Research Conference Proceedings Volume 2018 Issue 2
- تاريخ المؤتمر: 19-20 Mar 2018
- الموقع: Qatar National Convention Center (QNCC), Doha, Qatar
- رقم المجلد: 2018
- المنشور: ١٥ مارس ٢٠١٨
1 - 20 of 82 نتائج
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Automated Classification of Diabetic Retinopathy Severity: A Deep Learning Approach
المؤلفون: Rawan AlSaad, Sabri Boughorbel and Somaya Al-MaadeedBackground: Diabetic retinopathy (DR) is a damage to the retina caused by complications of diabetes and is the fastest growing cause of blindness. It is a major concern for the Qatari population, affecting about 40% of diabetic patients in Qatar. Automated DR classification techniques with high accuracy have a strong potential to help doctors in early diagnosis of DR and quickly routing patients who need medical interventions to a specialist. Most of the previous work utilized traditional machine learning techniques for the task of DR severity classification. Such techniques are based on “feature-engineering”, which involves computing explicit features designed by domain experts, resulting in models capable of detecting specific regions of DR damage or predicting the classification of DR severity. Recently, deep learning has emerged as an efficient technique that avoids such engineering. It shifts the burden of feature engineering to the design of general-purpose learning system which allows an algorithm to learn by itself the most important predictive features from the raw images, given a large dataset of labeled examples. Objectives: In this work, we studied deep learning techniques described in recent literature and combined it with our own ideas to develop a deep convolutional neural networks (ConvNets) architecture for the task of diagnosing diabetic retinopathy and classifying its severity from retina images. In addition, we explored the impact of the following parameters on the performance of the model: 1) number of fully connected layers, 2) number of units within each fully connected layer, and 3) batch size (number of training examples which will be forward/backward propagated through the network in one pass). Methodology: We trained the ConvNets model on the publicly available retina images dataset from the Kaggle competition for diabetic retinopathy detection. The dataset included labels with information about the presence of DR in each of the images, rated by a clinician on a scale from 0 to 4 (0: No DR, 1: Mild, 2: Moderate, 3: Severe, 4: Proliferative DR). The model was implemented using Theano, Lasagne, and cuDNN libraries and trained on two Amazon EC2 p2.xlarge instances (NVIDIA GPU K40). We used the same evaluation metric of the Kaggle competition, which is the Cohen's quadratic weighted Kappa function. In our case, Kappa is described as being an agreement between two raters: the agreement between the scores assigned by human rater (labels) and the predicted scores. Results: On the dataset of 30,262 training images and 4864 testing images, the model achieved a Kappa of 0.72. Our experimental results demonstrated that the number as well as the size of the fully connected layers does not have a significant impact on the model's performance. Moreover, it indicated that increasing the batch size does not necessarily speed up the convergence of the gradient computations. Conclusion: We have shown that convolutional neural networks have the potential to be trained to identify the features of Diabetic Retinopathy in retina images. Given the many recent advances in deep learning, we hope our work will open the door for many new examples demonstrating the power of deep learning to help solving important problems in medical imaging and healthcare. Keywords: deep learning, machine learning, diabetes, diabetic retinopathy, medical imaging.
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Hyperinsulinemia is associated with adipocyte hypertrophy and mitochondrial dysfunction
Insulin resistance is often associated with hypertrophy of adipocytes. Furthermore, hyperinsulinaemia may mediatechanges in cellular mitochondrial biogenesis and function. Therefore, the current study investigated the hypothesis that lower mitochondrial mass and mitochondrial uncoupling (whereby the electron transport is not used to drive ATP synthesis) is a feature of hypertrophied adipocytes.Methods. Adipose tissue (sub-cutaneous and omental) and blood was obtained from morbidly obese patients (BMI ≥ 40 kg/m2, age 29 ± 2.8 years), undergoing bariatric weight reduction surgery. Anthropometric data was recorded. The blood was used for systemic determination of glucose and insulin by commercial methods. The adipose tissue was separated into the adipocyte and stromal vascular fractions by collagenase digestion. Paraffinembedded adipose tissue was stained with Hematoxylin and Eosin and Image J software was used to determine cell size.Total RNA was isolated using Tri-reagent and the transcriptomeanalyzed using Affymetrix whole transcriptome arrays. The ArrayAnalysis.org statistics module using the Limma package of R/Bioconductor was used for the statistical comparison between High insulin subjects vs. Low insulin group. Genes were considered to be differentially expressed when their absolute log2 fold change (FC) > = 1, and p-value < = 0.05.Indices of mitochondrial function was examined in an in vitro model using 3T3-F442A murine differentiated adipocytes.Cellular lipid content and mitochondrial membrane potential(DΨm) were determined by confocal microscopy with 40 μMBodipy 493/503, a neutral lipid dye, and TMRE (30 nM).NADH/flavoprotein autofluorescence was measured in ‘multitracking’ mode, in which fluorescence was excitedalternately at 351 nm (signal measured at 435-475 nm; NADH)and at 458 (emission measured at >505 nm; flavoprotein). Theresting level of each coenzyme was expressed as a function ofthe maximally oxidized (with the uncoupler FCCP, 1 μM) andmaximally reduced signal (with cyanide, 1 mM). Oxygenconsumption was measured using a Clarke electrode and ATP generation using a luciferase assay.Results.The patient population was dichotomized into hyperinsulinaemic(>7.0 μU/ml) and normoinsulinaemic ( < 6.5 μU/ml) groups. The groups were matched for age and BMI. The hyperinsulianemicgroup, compared to those with normoinsulinaemia, had significantly greater numbers of hypertrophied adipocytes (p = 0.04). Pathway analysis showed that genes involved in the mitochondrial biogenesis (e.g: NRF1, GABPA, TFAM, POLRMT, MTERF and SP1) were comparable between the two groups. However several genes related the electron transport chain and ATP synthesis were significantly different between the hyperinsulinaemic and normoinsulinaemic groups (See table below). Expression of genes related to the electron transport and ATP synthesisComplex ? NDUFA4, ND3,ND6Complex IISDHA, SDHB, SDHC. Complex IIIUQCRH, UQCRFS1.Complex IVCOX5A, COX6A, COX7A. Complex VATP5A, ATP5E, ATP5HAdenine Nucleotide TranslocaterSLC25A4 In adipocytes characterized as having >40% intracellular lipid (hypertrophied), compared to those with < 20% (normal adipocyte), lipid, the rate of oxygen consumption increased(380%). DΨm was significantly reduced in cells with high,compared to those with low, intracellular lipid. Assessment ofredox state in lipid-engorged cells showed that flavoproteinswere more oxidized than NADH, consistent with a shift to b-oxidation as a dominant metabolic pathway. Resting levels ofboth coenzymes were significantly oxidized in lipid-engorgedcells compared to those with < span class = »bumpedFont15
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Association of levels of polybrominated diphenyl ethers in two fat compartments with increased risk of insulin resistance in obese individuals
المؤلفون: Mohamed Elrayess, Murad Helaleh, Ilhame Diboun, Nada Altamimi and Aishah LatiffMurad Helaleh1, Ilhame Diboun2, Nada Altamimi1, Aishah Latiff1, Mohamed Elrayess1* 1Toxicology and Multipurpose Lab, Anti Doping Laboratory Qatar, Sports City, Doha, Qatar. 2 Department of Economics, Mathematics and Statistics, Birkbeck, University of London, London WC1E 7HX, UK. Corresponding author: [email protected] diphenyl ethers (PBDEs) represent a class of widely utilized flame retardants [1]. With over 200 congeners that vary by the extent of halogenations, various PBDEs can leak freely into the environment [2, 3]. Despite cessation of their manufacturing, concerns of their bioaccumulation remain [4-6] due to their stability in products manufactured before the ban and recycled materials [1]. With their high lipophilicity, PBDEs tend to accumulate in adipose tissue, potentially altering the function of this endocrine organ by increasing lipolysis and decreasing glucose oxidation, causing increased risk of metabolic disease including obesity, insulin resistance and type 2 diabetes [7]. Exposure to PBDE-47, for example, during the early post-natal period was shown to induce disturbance in glucose metabolism causing insulin resistance in susceptible mice [8]. In this study, levels of various PBDEs were assessed in subcutaneous and omental adipose tissues from 33 obese and morbidly obese patients (11 insulin sensitive and 22 insulin resistant) and their correlation with mediators of metabolic disease were established. Our results suggested that out of 22 detectable PBDEs in subcutaneous and omental adipose tissues, PBDE99, 28, 47 and 126 were significantly higher in insulin resistant individuals compared to their insulin sensitive counterparts. When considering PBDEs congeners, penta congeners as a group were also higher in insulin resistant individuals compared to insulin sensitive counterparts, while no significant differences were detected in mono, tri, tertra, hexa, hepta and octa congeners between the two studied groups. This data suggest that accumulation of various PBDEs in human adipose tissues obtained from obese individuals is associated with increased risk of insulin resistance. Further investigation of the functional relevance of these associations is currently underway. This study is partly funded by QNRF's grant number NPRP6-235-1-048. References 1. Birnbaum, L.S. and D.F. Staskal, Brominated flame retardants: cause for concern? Environ Health Perspect, 2004. 112(1): p. 9-17. 2. Chen, D. and R.C. Hale, A global review of polybrominated diphenyl ether flame retardant contamination in birds. Environ Int, 2010. 36(7): p. 800-11. 3. Ernest, S.R., et al., Effects of chronic exposure to an environmentally relevant mixture of brominated flame retardants on the reproductive and thyroid system in adult male rats. Toxicol Sci, 2012. 127(2): p. 496-507. 4. Kelly, B.C., et al., Bioaccumulation behaviour of polybrominated diphenyl ethers (PBDEs) in a Canadian Arctic marine food web. Sci Total Environ, 2008. 401(1-3): p. 60-72. 5. Mercado-Feliciano, M. and R.M. Bigsby, Hydroxylated metabolites of the polybrominated diphenyl ether mixture DE-71 are weak estrogen receptor-alpha ligands. Environ Health Perspect, 2008. 116(10): p. 1315-21. 6. Sjodin, A., D.G. Patterson, Jr., and A. Bergman, A review on human exposure to brominated flame retardants–particularly polybrominated diphenyl ethers. Environ Int, 2003. 29(6): p. 829-39. 7. Hoppe, A.A. and G.B. Carey, Polybrominated diphenyl ethers as endocrine disruptors of adipocyte metabolism. Obesity (Silver Spring), 2007. 15(12): p. 2942-50. 8. McIntyre, R.L., et al., Polybrominated diphenyl ether congener, BDE-47, impairs insulin sensitivity in mice with liver-specific Pten deficiency. BMC Obes, 2015. 2: p. 3.
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Effect of C1q Tumor Necrosis FactorRelated Protein 11 Ctrp11 On Macrophages
المؤلفون: Ilham BettahiBettahi I1-2, Ramanjaneya M1-2, Jerobin J1-2, Sivaraman SK1, Rasha Alsiddig3, Mohammad RM4, Skarulis MC1-2 and Abou-Samra AB2-3. 1Translational Research Institute, Academic Health System, 2Department of Medicine, 3Qatar Metabolic Institute, Hamad Medical Corporation, Doha, Qatar, 4Karmanos Cancer Center, Wayne State University. Background: Obesity is a major risk factor for cardiovascular disease, increasing the risk of hypertension, hyperglycemia, and dyslipidemia, recognized as the metabolic syndrome. Adiponectin paralogs designate as C1q/TNF-related protein (CTRPs) have recently emerged as key regulators of metabolism and is a core component in the interrelationship between insulin resistance, adiposity, and inflammation. CTRP-11 functions as an adipose stroma-derived regulator of adipogenesis. Aim and objectives: The aim of this study is to characterize the anti-inflammatory potential of the CTRP-11. Methods: Cell lines differentiation: Human THP1 cells were maintained in RPMI-1640 supplement with 10%FBS. Cells were seeded in 24 well and stimulated with PMA for 48 hours to differentiate them to macrophages and rested for 24 hrs. For all stimulation experiments, cells were grown for overnight in serum-free media. Cells were then treated with CTRP11 for 24 hours and then re-stimulated with LPS for 6 hrs. Cells were collected for RNA extraction and genes expression using Real-Time PCR. FACS analysis: After differentiation and incubation with LPS and LPS/CTRP11, Cells were stained with human anti-CD206 and anti-CD163. Following incubation, cells were washed, and fluorescence compared to unstained. All data were analyzed using FlowJo software. Results: Our preliminary data provide that CTRP11 decreased both IL-6, TNF-α and NF-kb expression of mRNA level in THP-1 macrophages activated with lipopolysaccharide (LPS) (p < 0.005), compared to (LPS) alone. THP-1 macrophages showed and increased in M2 polarization marker CD206 and CD163 after incubation with LPS/CTRP compared to LPS alone. Conclusion: Future studies are in progress to further assess the effects of adiponectin paralogs (CTRP11) on cytokine excretion by ELISA on Human macrophages M1 and M2. Abbreviation: LPS: lipopolysaccharide; PMA: phorbol 12-myristate 13-acetate.
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Viscoelastic behaviour of Bovine Myocardiam and valvular tissue: Applications in Bio prosthetic heart valve with enhanced properties
المؤلفون: MD Anwarul HASAN, Alap Ali Zahid, Raza ur Rehman Syed, Noorunnisa Khanam and Hani A. AlhadramiCardiovascular diseases are among the major causes of morbity and mortality. Particularly, the prevalence of heart valve disease(damaged heart valve leaflet) is one of the most common ailment. In elderly people, every year 30,000 patients are treated with heart valve replacement surgeries in the developed countries. Mechanical and bioprosthetic heart valves are commonly used in heart valve surgeries. While mechanical valves require the patient to be on blood thinning agent, rest of the life, bioprosthetic valves have only limited life span. Adequate knowledge of the biomechanics of nano-microscale structure and the viscoelastic properties of the native (bovine) heart valves can pave the ways for enhancing the strength of bio-prosthetic heart valves. In present work, we measured the viscoelastic and structural properties of the native bovine myocardiam and valvular tissue of heart valve. These heart valves were taken from bovine hearts and cryopreserved as necessary. The rheological and viscoelastic properties of heart valves were investigated by fixing in formaldehyde and phosphate buffer solutions (PBS). The samples were then tested in SEM (Scanning Electron Microscope) to investigate the microstructure of valve leaflets. Using Dynamic Shear Rheometer, the critical parameters such as modulus of elasticity, storage modulus, loss modulus, complex modulus, complex viscosity and the oscillatory shear properties were thoroughly investigated. Results show that the rheological properties vary with different chemical fixation effects. Chemical fixations like formaldehyde fixation were improving the rheological properties of heart valves. However, there is no significant influence of different time periods of fixations on mechanical properties. The complex modulus as well as the compression and storage moduli of the sample fixed with formaldehyde showed the satisfactory values after the fixation. It was indicating the mechanical strength has improved in terms of its structure, as much as solid/rigid as before the fixation. Also, the viscosity of fresh valve was higher, showing that the aldehyde fixation alters the mechanical property of the heart valve. Through the creep tests, it was investigated that the fixation of the heart valves did affect the viscoelasticity and mechanical properties of the heart valves. The valves become stiffer when they were fixed with formaldehyde. The reactions were less by a whole order of magnitude. However, by fixing the sample in formaldehyde we observed that the aortic valve had much more strength than the fresh sample. Another proof of how the aldehyde fixation drastically affected the stiffness of the valve was in the fact that the extension of the aldehyde-fixed valve under a stress of 5 kPa was less than that of the fresh valve at 0.5 kPa. These outcomes provide significant insights into the correlations between the microstructure and mechanics of the heart valves and their macro scale behaviors under various conditions. These results were modeled using Computer Aided Engineered software. The software can help scientists in evaluating the performance of tissue engineered heart valves with natural heart valves.
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Overexpression of Calreticulin in endothelial cells changes insulin trascytosis
المؤلفون: Tatiana Carneiro Lobo, Rajja Dalloul and Nasrin MesaeliCarneiro-Lobo T.C., Dalloul R.S.D., Mesaeli N. Department of Biochemistry, Weill Cornell Medical College in Qatar, Doha, Qatar. Introduction: The incidence of diabetes and obesity has been rising world wide in the past few decades. In the Gulf Cooperation Council (GCC) a rapid increase in the prevalence of diabetes has been reposted in the past few years. In Qatar the incidence of diabetes is 16.7% in the Qatari population that is almost 3 times higher than the incidence of diabetes in UK. Type 2 diabetes mellitus is a growing public health problem and a major cause of cardiovascular disease in the United State. Type 2 diabetes is associated with systemic insulin resistance, which promotes hyperglycemia, and it has been proposed that these metabolic abnormalities account for increased cardiovascular risk. Endothelial dysfunction contributes to the pathogenesis and clinical expression of atherosclerosis and has been linked to type 2 diabetes mellitus and insulin resistance. Transport of insulin across the microvasculature is necessary to reach its target organs and is rate limiting in insulin action. The two possible mechanism of this movement is either through leaky tight junction in vascular endothelial cell layer or via transcytosis through these endothelial cells. Therefore, we hypothesized that overexpression of calreticulin would reduce insulin transport to the target tissue due to onset of endothelial dysfunction. Methods and Results: To test our hypothesis, we used genetic approaches to overexpress calreticulin (CRT). For in vitro experiments CRT was overexpressed using a Lentiviral-CRT-RFP to infect Human Umbilical Vein Endothelial Cells (HUVEC). For ex vivo studies we used endothelial cels isolated from our endothelial specific CRT overexpressing transgenic mice (ECCRT+). We examined the uptake of fluorescently labeled insulin in the endothelial cells. CRT-HUVEC and WT-HUVEC were incubated with 25 μg of FITC-insulin for 30 mins and 60 mins. We found that CRT-overexpressing cells reduce the transcytosis of insulin through the endothelial cells compared to control. The primary endothelial cells were isolated using columns containing PECAM (CD31) coated beads. Cells were then characterized by detection of CD31 (PECAM) and Von Willebrand factor (vWF) expression by immunofluorescence and western blot. After confirming the endothelial identity of our primary cells (ECCRT+) they were incubated with Alexa-647 insulin for 30 min or 60 min. Confocal microscopy was carried out to examine insulin uptake and transcytosis. Our data illustrate a reduction in insulin trancytosis in ECCRT+ endothelial cells as compared with WT cells. To evaluate how Calreticulin affects insulin trancytosis in vivo in whole animal, ECCRT+ mice and WT-mice were used. Alexaflour-647 insulin (1.2 μg/L) was injected via tail vein of ECCRT+ mouse and WT-mouse. To label the surface of endothelial cells, 20 μg/L FITC-isolectin was injected via tail vein following insulin injection. 30 mins after the injection mice were euthanized and tissue (lung, liver, heart and retina) were isolated, fixed and embedded for cryosections. Tissue sections were then mounted on slides and examined by confocal microscopy. We observed a lower concentration of insulin in cell membrane of endothelial cells of vascular wall in lung, liver, heart and retina of ECCRT+ mouse than WT-mice. Finally, we examined the leakiness of the vascular wall in our ECCRT+ mouse model. In these experiemnts we injected 2.5 mg/ml FITC-Dextran in the tail vein for 30 min. After euthaniasia, mice tissue was imaged under a Ziess flourescnet microscope to evaluate leakage of the flourescet signal in the tissue. Fluorescent images from the lung, liver and heart were collected and illustrated an increase in the leakiness of vascular wall of the small vessels in the ECCRT+ mice as compared to the WT mice. Conclusion: Taken together, our results illustrate that increased calreticulin expression in endothelial cells affect endothelial cell function, increase the vascular permeability and reduce the transcytosis of insulin through the endothelial cell of vasculature. The impaired insulin export from the vascular wall to the target tissue could contribute to the onset of insulin resistance and diabetes in the ECCRT+ mice which we have observed in our other studies on these mice. This is the first report to link calreticulin expression level and insulin transport in intact animal. Acknowledgment: This research was made possible by a grant by QNRF, NPRP07-208-3-046.
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Electrospun polymer nanocomposite scaffolds containing metal oxide nanoparticles for diabetic wound healing
المؤلفون: Robin AugustineRobin Augustinea, Noorunnisa Khanama, Hany Elsayed Mareib, Sabu Thomasc, Ala-Eddin Al Moustafad, Anwarul Hasana a College of Engineering, Qatar university Doha, Qatar bBiomedical Research Centre, Qatar university Doha, Qatar cInternational and Inter University Centre for Nanoscience and Nanotechnology, Mahatma Gandhi University, Kottayam – 686 560, Kerala, India. dCollege of Medicine, Qatar university Doha, Qatar Abstract It is very important to treat diabetic foot injuries at early stage since even minor wounds can turn into serious foot ulcers which can lead to the amputation of the entire foot if not treated early. The management of diabetic foot ulcers requires the use of appropriate wound dressings to provide a moist wound environment and protect from infection. Large number of polymeric materials has been tried for wound coverage applications with many successful outcomes, but the search for an ideal wound dressing material which can enhance diabetic wound healing is still continuing. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate), commonly known as PHBV has got a lot of attention in biomedical applications due to its biocompatibility and biodegradability Electrospinning is a robust technique that can produce highly porous membranes composed of nano or submicron fibers from polymer solutions. Formation of active blood vessel network through an implanted wound dressing is one of the most important issues in the treatment of diabetic wounds. Ability of metal oxide nanostructures to promote angiogenesis and wound healing is already established. Thus, in the present work, electrospun PHBV wound dressings containing metal oxide nanoparticles were fabricated and characterized. Our results demonstrated that metal oxide nanoparticles in the wound dressings enhanced human cell adhesion and their migration. Further, angiogenic property of the membranes was enhanced as evident from chicken chorioallantoic membrane assay and leads to the enhancement of diabetic wound healing. Present study strongly suggest the potential application of metal oxide nanoparticles incorporated PHBV scaffolds in promoting angiogenesis and their effective use in diabetic wound healing.
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Electrospun polymer nanocomposite scaffolds containing metal oxide nanoparticles for diabetic wound healing
Background: Most of the evidence -so far- in support of the link between Transient Ischemic Attack (TIA) and the development of future stroke are -in fact- based on epidemiological rather than scientific evidence. Meanwhile, Current prediction models for long-term prognosis in TIA and stroke patients have limited validity as discrimination between patients at high risk and patients at low risk is relatively poor. Although the ABCD2 prediction model seems to be most adequate because of its applicability in clinical practice, the American Heart Association pointed out that validated prediction models for long term cardiovascular risk in patients with ischemic stroke or TIA were not available. Furthermore, it has been suggested that all these stroke-based prediction models were derived from trial populations with certain inclusion and exclusion criteria. It could therefore be argued that the best fitted model for everyday practice will probably need to be derived from a consecutive stroke/TIA population without exclusion criteria. Improvements (such as stronger predictors of outcome) are therefore needed. Aims: This study investigates the prevalence of microalbuminuria in patients who have suffered a TIA for the first time. The aim is to identify a subgroup of TIA patients who are at higher risk of developing future cerebrovascular events. Methods: This is an observational cohort study with two arms (in Qatar and UK). The Qatari arm involved 56 patients with acute TIAs or small stroke (TIAs with tissue evidence of infarction), attending a local hospital in Qatar; whereas, the UK arm involved 74 first time TIA patients, attending a TIA Clinic at a local hospital in the UK. Microalbuminuria was first measured by calculating the Albumin/Creatinine Ratio (ACR). Urine samples (with and without microalbuminuria) were then examined using SDS-PAGE electrophoresis. Protein bands were identified by their rate of migration in comparison with standard molecular weight (MW) markers. Results: The Qatari arm of the study recruited 56 patients (mean age 55.50 years); 35 Males: 21 Females), attending a Stroke/TIA Clinic in Qatar. 19 (33.92%) TIA patients showed evidence of microalbuminuria (30-300 mg/24 hr) and 37 (66.08%) showed normal albuminuria ( < 30 mg/24 hr). The UK arm of the study recruited 74 first TIA patients (mean age 74.75 years; age range 52-91); 38 Males: 36 Females). 25 (33.78%) TIA patients showed evidence of microalbuminuria and 49 (66.22%) showed normal albuminuria. Out of the 25 TIA patients with microalbuminuria, 92% of them have a blood pressure of more than 140 mmHg. SDS-PAGE electrophoresis of urine samples obtained from patients recruited (for both arms of the study) revealed a similar pattern of 3 major protein bands. Band (A) is heavily stained, representing albumin (MW = 70 kDa) in patients with micro-albuminuria, and less intensity in patients with normal-albuminuria. Band (B) was shown in all urine samples of patients with microalbuminuria, but not in patients with normal-albuminuria. Its position on the gel is roughly equidistant between bands A and C. Band (C), denoting a slower migration band, representing Tamm-Horsfall protein. Tamm-Horsfall protein is suspected since not only is it the most abundant protein in urine after albumin, but also its position is in concordance with the relative molecular weight of Tamm-Horsfall protein (between 85 and 110 kDa). The intensity of this band is generally not as great as band A. Other bands (MW < 50 kDa and < 40 kDa) were also seen; they may represent degradation products of albumin due to storage. Discussion: Microalbuminuria has been proven to be a predictor of cardiovascular disease and mortality in both diabetic and non-diabetic patients, and it is a reflection of an overall vascular damage. This study aims to identify a subgroup of TIA patients who are at higher risk of developing future cerebrovascular events. Our data confirmed that microalbuminuria is very common in TIA patients as one third of participants (in both arms of the study) presented with microalbuminuria, most of whom have a history of high blood pressure. However, it is important to highlight here that participants in the Qatari cohort are much younger and their microalbuminuria is more severe than the UK cohort. This might be due to the severity of their condition, the presence of co-morbidity, ethnicity and genetic susceptibility. With such a high prevalence of microalbuminuria (in first time TIA patients), such a prognostic marker cannot be ignored in TIA Clinics. There is now a case for microalbuminuria to be considered for possible adding it to the current ABCD2 predictive model, taking into account the fact that microalbuminuria can now be easily measured using a urine dip stick testing. The clinical applications of our findings may include an aggressive approach to antihypertensive management. Conclusion: Microalbuminuria following TIA is likely to be an added marker of risk and could indicate a more aggressive approach to hypertension management or the choice of ACE inhibitors angiotensin 2 receptor blockers over other antihypertensive drugs. The novelty of this project stems from the fact that it investigates two predictive makers; one biochemical (microalbuminuria, presented in this study) and one physiological (auto-regulation of cerebral blood flow, still being analyzed). No previous research has combined the two predictive markers together in a cohort group of first time TIA patients. These two predictive parameters will provide us with more evidence to predict further stroke and whether current intervention is sufficient enough to prevent future stroke. If this is proven to be correct, both predictors will add more validity to the current conventional risk models predictors. If there is such a link between these two measures then changes to the regulation of blood flow in the brain can be predicted by a simple urine test. This will help predict how well patients will recover after TIA. Furthermore, if microalbuminuria is associated with impaired cerebral auto-regulation (following TIA) then one might take more caution with anti-hypertensive treatment early after TIA. By identifying impairment in auto-regulation this study may provide an important reason for caution which may otherwise be overlooked. «This study was made possible by grant NPRP 6-565-3-141 from Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the author[s].»
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Effects Of Gestational Diabetes Mellitus On Hematopoietic Stem cell quality and IL6 Amount
المؤلفون: Tamer ElhusseiniGestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy (1), Maternal glucose and lipid metabolism changes substantially during normal pregnancy, In women with GDM, fasting insulin and fasting glucose concentrations are elevated. Also, women with GDM have a lower insulin sensitivity compared to controls and the difference is most evident before and during early pregnancy (2). Gestational diabetes mellitus has proven it»s effects on many variables of pregnancy and so it»s effect on umbilical cord blood (UCB), which is increasingly used as an alternative source of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) for bone marrow transplantation and other therapeutic uses, And for successful outcomes of cord blood transplantation certain criteria are used in UCB banks include the TNC count, percentage of CD34, CFU and the volume of blood (3) As many variables that may affect the quality of hematopoietic stem cells are still under study and research, And gestational diabetes mellitus is a disease expected to increase by 20 fold, AS regard it»s effect on hematopoietic stem cell and IL6 it»s found that «The proportion of CD34+ CD45 HSPCs among the nucleated cells was significantly higher in the cord blood samples of neonates born to mothers with GDM compared to neonates born to non-diabetic mothers.»(4) Also, it»s found that IL-6 concentrations are increased in women with current GDM (2). Another study reported that: the CD16+CD56 − NK cells was increased, while IL-2 was lower in maternal blood with GDM. The placental extravillous layer of the gestational diabetic mothers showed high levels of IL-4, IL-6, IL-10, IL-17, and IFN- and low levels of IL-1 and IL8, whereas the placental villous layer contained high levels of IL-17 and IFN(5). In this study we provide atrial for knowing whether the cord blood unit of gestational diabetic mother fulfilling the appropiate criteria for banking, As in previous studies all what had discovered is minimal non concolusive data about whether GDM unit fulfilling the normal criteria for banking or not.
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Generation of induced pluripotent stem cells from insulin resistant Qatari patients
Insulin resistance (IR) is a precursor and accelerating factor for Type 2 diabetes (T2D), the greatest health challenge facing Qatar and the world today. Psoriasis, is an immune-mediated, chronic skin disorder that can aggregate in families, because of its strong genetic predisposition. It has been found that patients with psoriasis for more than two years, regardless the severity of the disease, are at a very high risk of developing insulin resistance and diabetes. Although several studies highlighted the link between IR and skin disorders, no reports studied the relationship between IR, T2D, and epidermal dysfunction using induced pluripotent stem cells (iPSCs). Therefore, our aim in this study was to generate patient-specific hiPSCs from IR Qatari patients (associated with psoriasis or T2D) and differentiate them into insulin target cells. Blood samples were collected from Qatari individuals with a family history of IR associated with T2D or psoriasis as well as from healthy individuals. The Ficoll-Paque density gradient method was used to separate the peripheral blood mononuclear cells (PBMCs). The isolated PBMCs were cultured in vitro for 5 days in StemPro-34 culture medium before transduction. PBMCs were reporgammed using Sendai viral vectors encoding four pluripotency factors including OCT4, SOX2, C-MYC, and KLF4. After 20-30 days of the transduction, several undifferentiated colonies of high morphological quality (defined border and high nuclear to cytoplasmic ratio) were manually picked up and transferred to new matrigel-coated plates to establish different clones. Several hiPSC clones were established from each individual (sample) and only three clones were maintained after extensive characterization of all clones. The generated hiPSC clones were characterized using different techniques including immunostaining, RT-PCR, Western blotting, alkaline phosphatase assay, embroid body (EB) formation, karyotyping, and hPSC ScoreCard assay. H1-human embryonic stem cell (H1-hiESC) line was used as a positive control in all experiments. Similar to hESCs, hiPSC clones expressed pluripotency markers, such as OCT4, SOX2, NANOG, KLF4, C-MYC, SSEA4, TRA-60, TRA-81, REX-1, DPPA4, and TERT at mRNA and protein levels. All hiPSC lines showed standard hESC morphology, normal karyotype and stained positive for alkalaine phosphatase. Only the hiPSC lines that showed similar characteristics as those of hESCs were maintained and expanded in culture. To confirm the pluripotent ability of the generated hiPSCs, we used EB technique to differentiate patient-specific hiPSCs into three germ layers in vitro. Immunostaining and RT-PCR analyses showed that these hiPSCs can differentiate into endodermal (SOX17+/FOXA2+), mesodermal (BRACHYURY+) and ecodermal (NESTIN+) lineages. To further validate the multilineage differentiation potential of the generated hiPSCs, we used the hPSC ScoreCard assay in vitro. These findings indicate that hiPSCs generated in this study are pluripotent, fully reprogrammed stem cells having the ability to differentiate into any cell type of the body. Thus, we will differentiate patient-specific hiPSCs into insulin target cells carrying the genetic background of the patients to identify signaling mechanism involved in the inherited form of IR and to understand the genetic link between IR, T2D, and psoriasis. To our knowledge, this is the first study to generate hiPSCs from diabetic and psoriatic patients in the MENA region.
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Obesity is associated with the upregulation of TLR4 protein but not associated with polymorphisms of TLR4D299G TLR4T399I
المؤلفون: Mariam Alwakeel, Afnan O. Galash, Amina Saleh, FadelMooza Alkhanji and Nasser M. RizkTitle: Obesity is associated with the upregulation of TLR4 protein but not associated with polymorphisms of TLR4D299G TLR4T399I.Background: Toll-like-receptor 4 (TLR4) is a pathogen-specific receptor, expressed in white blood cells, adipocytes, and other metabolic cells. Lipopolysaccharides (LPS) and free fatty acids (FFA) can act upon TLR4 and activate systematic inflammation that may lead to obesity and metabolic syndrome (MS).Aim: The aim of this research was to investigate the association of TLR4 polymorphisms of TLR4D299G TLR4T399I, with obesity and metabolic syndrome components in young adult female Arab subjects.Methodology: A prospective cross-sectional study was performed on female students from Qatar-University. The subjects were classified according to BMI classifications by WHO category into two groups: “obese; n = 69” and “non-obese; n = 136”. Anthropometric measurements included weight (kg), height(m), waist circumference (WC) were assessed, and the body mass index (BMI) was calculated. Several biochemical assays were done to determine glucose and lipid profile. Plasma concentration of Interlukin-10 (IL-10) was measured using ELISA assay. Plasma concentration of IL-6, MCP-1, leptin, and insulin was measured using the multiplex Luminex assay. Also, fresh blood samples were used to measure TLR4 protein expression using flow cytometry assay.Results: TLR4D299G/T399I carriers had no significant association with obesity indicators; body mass index (BMI), body fat percentage (%BF), and waist circumference (WC). Haplotype analysisof TLR4 D299G/T399I showed that GT carriers of TLR4 D299G/T399I had a significant association with increased risk of insulin resistance with (odds ratio = 4.73), 95% CI (1.19- 18.90), (P-value = 0.016). Increased level of leptin was associated with obesity phenotype by BMI, WC, and %BF. In addition, up-regulation of TLR4 protein increased significantly in obese subjects by 1.2 fold over the non-obese, with (P-value = 0.006). Conclusions: TLR4 D299G/T399I polymorphism is associated with increased insulin resistance, a core component of metabolic syndromes but not with obesity. In addition, the up-regulation of TLR4 in obese subjects may be related to insulin resistance with increased leptin suggesting that increased free fatty acids may be a possible link to act as a ligand for TLR4.
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The role of the autophagy pathway in phagosome formation in macrophages interacting with adipocytes
المؤلفون: Sara AlhousseinyIntroduction The interactions between macrophages and inflamed white adipose tissue (WAT) have been implicated to play a role in several diseases including diabetes mellitus type 2, obesity, and breast cancer. Macrophages degrade dead adipocytes through a process known as “exophagy”, which is extracellular lysosomal hydrolysis. They form crown-like structures (CLSs), encircling dead or dying adipocytes. The macrophages create a tight seal on the adipocytes and their lysosomal contents are secreted into these seals or compartments which are known as lysosomal synapses. This project was investigating the way that macrophages digest dead adipocytes, specifically if the autophagosome protein marker LC3 is recruited to the apoptotic cell phagosome in CLS macrophages. Autophagy and phagocytosis have traditionally been thought of as completely separate processes, but recent studies have shown that there are some autophagy proteins which are involved in the phagocytosis of apoptotic cells (Florey et al, 2012). These autophagy proteins can lipidate microtubule-associated protein light chain 3 (LC3) onto phagosomes in a way that is independent of the autophagosome. This recruitment of autophagy proteins LC3 and Beclin1 to phagosomes has been called LC3-associated phagocytosis, or LAP, and ends in the acidification and lysosome fusion with phagosomes. Even though LAP was originally only thought to be used for the phagocytosis of pathogens, autophagy is also being shown to play a role in apoptotic cell engulfment, with some research showing that autophagy proteins play a role within phagocytes (such as macrophages) for regulating the degradation of apoptotic cells. Methods The adipocytes used in this model system were differentiated 3T3 L1 cells. In order to induce apoptosis in the adipocytes, they were incubated with 25 nM TNF-a for 24 hours, or on one occasion exposed to 365 nm UV radiation for 1 hour. The macrophages that were used in this project were from the J774 cell line and also the stable cell line J774 GFP LC3. In order to replicate the in vivo setting of macrophages surrounding a dead adipocyte, the in vitro CLS cell culture model was carried out based on preliminary work that had been already established in the Maxfield lab. All fluorescence microscopy experiments were carried out using the confocal microscope Zeiss LSM 880 equipped with the high resolution detector, Airyscan. After the adipocytes were incubated with TNF-a for 24 hours to induce apoptosis, they were labeled with NHS-Alexa633, and the macrophages were trypsanized in order to add them to the adipocytes. Several different time points were used for this experiment, starting every 30 min from 30 min post addition to 210 minutes. Macrophages were added to each dish containing adipocytes and the dishes were incubated for the specified times. At the end of the incubation time, the macrophages and adipocytes were fixed by adding PFA for 10 min, and then the PFA was washed off and blocking IF solution was added for 1 hour. Primary antibody diluted in BSA was added after the blocking step. The dishes were then left in the cold room overnight. The following day the secondary antibody was added, and left for 60 min at room temperature. This was then washed off and the dishes were left in PBS until imaging with the confocal microscope Zeiss LSM 880 equipped with the high resolution detector, Airyscan. In order to have a control for the experiment, previous researchers had used zymosan, since it is known to induce LAP, and that LC3 is translocated to the zymosan containing phagosome. We therefore had dishes with macrophages and zymosan instead of the apoptotic adipocytes. There were also dishes solely with macrophages imaged however these were also simply a control and not leading to any results. Results The results obtained from the confocal imaging of the macrophages with apoptotic adipocytes were consistent in showing no recruitment of LC3 to the macrophage-adipocyte contact sites. The adipocytes were labeled in blue with the NHS-Alexa633, the macrophages and LC3 with the Alexa546, and the plasma membrane of the macrophages were labeled in green with the Alexa488. Discussion The results of the study showed that the hypothesis was rejected, in that LC3 is not recruited to the phagosome in the digestion of dead adipocytes by macrophages, and therefore the process is not a form of LC3- associated phagocytosis. Although past research has shown that the ideal time to image LC3 being recruited would be at 120-150 minutes, images taken both before and after those times yielded no results in this case. Because this experiment had never been done before by the lab or by any other researchers, there was no reason to either specifically refute or support the fact that LC3 would be involved and the process would be LAP for CLS macrophages with dead adipocytes. In the future, the search for regulatory molecules that act in this process may lead to improved strategies to prevent or treat type 2 diabetes, metabolic disorders and certain types of cancers.
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The Role of Soluble Adhesion Molecules in Type 2 Diabetes Mellitus
المؤلفون: Ola AljammalBackground: Diabetes mellitus (DM) is a chronic metabolic disorder that is steadily increasing worldwide and is a leading cause of morbidity and mortality. As reported by the World Health Organization (WHO), 346 million people are currently suffering from diabetes worldwide, and the number of deaths related to diabetes is expected to double by 2030. This highlights the importance of continued research and the need for novel methods to both prevent and treat this pandemic. Endothelial dysfunction plays a central role in the pathogenesis of diabetes mellitus and its vascular complications. The damage to the endothelium results in the release of soluble forms of adhesion molecules into the circulation and their concentrations are thought to correlate with endothelial cell activation or dysfunction. Aims: To determine the serum levels of soluble vascular cellular adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) in type 2 diabetes mellitus (T2DM) and their association with macrovascular and microvascular complications. Methods: A total of 20 blood samples were collected form diabetic patients at the Hamad Medical Corporation (HMC) between 2010 and 2011. The control blood samples were obtained from non-diabetic female students at Qatar University in Fall 2017. Serum concentrations of sICAM-1 and sVCAM-1 level were determined using magnetic bead multiplex assay. Results: The levels of sVCAM-1 (P- value 0.000005) and sICAM-1 (P- value 0.04) were both significantly higher in T2DM patients compared to the control group. There was a further increase in the levels of sVCAM-1 and sICAM-1 in diabetic patients with complications. There was a positive but not significant correlation between hyperglycemia, sVCAM-1 and sICAM-1 levels. Conclusion: T2DM is associated with high levels of sVCAM-1 and sICAM-1. Hyperglycemia is a major factor causing endothelial dysfunction in T2DM and the release of soluble adhesion molecules.
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The Effect of Protein Supplementation on Body Muscle Mass and Fat Mass in Qataris PostBariatric Surgery: A Randomized Controlled Trial RCT
المؤلفون: Fahad Hanna, Sahar Dahawi Al-Shamari, MOHAMED Aly ElSherif and Wahiba WahidBackground and objectives: Obesity is a chronic medical condition characterized by an accumulation of excess fat in the body that may lead to negative health consequences. Bariatric surgery has been shown to be the most effective type of interventions to achieve and sustain significant weight loss in morbidly obese people. The objective of this study was to examine the effectiveness of protein supplementation in reducing the risk of developing protein malnutrition and low muscle mass, in post-bariatric patients in Qatar. Methodology: This study is a double-blinded randomized control trial. Recruitment of participants began in early 2017 following the ethical approval of the trial (HMC IRB approval no. 16433/16). The intervention group received protein supplement that contain 20 g of protein while the placebo group received zero protein supplement. All participants were followed up for 1 month post-surgery. Randomization was done on a weekly basis within blocks of 8 or 10 patients. Independent Sample-T Test and Paired Sample-T Test were performed to assess the effect of the intervention. Results: The mean weight loss in the control group was 9.6 kg, while the intervention group mean weight loss was 10.7 kg (p = 0.03). Change in muscle mass percentage was +0.50% in the placebo group, and +2.3% in the intervention group (P = 0.149). Fat percentage change in the placebo group was − 1.6% and − 2.6% in the intervention group (P = 0.153). The percentage change in Albumin in the placebo group was 2.76% and 9.71% in the intervention group (P = 0.031). Conclusion: Our study has confirmed findings from multiple studies that protein supplementation in post-bariatric surgery patients is a successful intervention for healthy and balanced weight loss. This is yet another endorsement that surgery alone cannot put an end to obesity and must be combined with well-structured nutritional education so patients do not go back to their old habits and put the weight back on.
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Evaluation of Antidiabetic and Antihypertensive Potential of Some Traditional Desert Food Plants of Qatar Using in Vitro Assays
المؤلفون: Tahra ElobeidNumerous studies have shown that food plants, the source of basic nutritional components may also possess an additional bioactive therapeutic properties associated with the prevention of diseases such as type 2 diabetes and its related complication, hypertension. The incidence of type 2 diabetes in Qatar is one of the highest in the world. In the present study, four edible plants from Qatar were selected to analyze the phenolic bioactives and their potential health benefits with relevance to managing type 2 diabetes and hypertension using in vitro enzyme assays. High antioxidant activity along with high total soluble phenolics associated with high in vitro enzyme inhibitory α-glucosidase, moderate α-amylase and ACE inhibitory effects was shown by aqueous extracts of Cynmorium coccineum. Malva parviflora and Glossonema edule had moderate antioxidant potential, total soluble phenolics and ACE inhibitory potential. Edible plants like Cynmorium coccineum that is also suggested to possess other medicinal properties has a high potential for diet-based solutions in combating, preventing and managing early stage of type 2 diabetes coupled to overall healthy life style and pharmacological management strategies. This study provides the biochemical rationale for further animal and clinical studies to understand the health benefits of edible plants of Qatar as dietary strategies for chronic disease management.
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Image Stitching System With Scanning Microscopy for Histopathological Applications
المؤلفون: Muhammad Ali AkbarHistopathological analysis of biopsy or surgical specimen is a common clinical practice for diagnostic purposes. Essentially, the process involves slicing the biopsy or surgical sample into very thin slices, placing them on glass slides and viewing them under microscopes. Predominantly, the placement, positioning, and view control is done manually by the pathologists in most of the clinics and hospitals because of which the diagnosis remains heavily dependents upon the experience and performance of the pathologist. Moreover, the slide scanning relies predominantly on the slide placement accuracy. A misaligned slide will create misaligned images which can either miss out information or have blank artifacts due to image frame placement methodology. In this paper, a simple ‘add-on’ system has been presented that can be used to scan single slide with moderate speed and produces the image on a Virtual reality headset to provide the submerged feeling. Most importantly, it utilizes advanced image stitching algorithms to align the frames from the captured video stream of the slide to produce a very accurate image with a very large size. The stitching is done using the standard feature-based algorithms which have been modified in this work by incorporating affine blending maps to combine the features into final image. It has been found that the image stitching algorithm provides the stitched image with less than 2% error for the given test images. Research Methodology: The proposed approach utilizes a standard clinical microscope with 10x, 40x, and 100x magnifications. The microscope has x-y movable stage which is moved by the pathologist using two vertical knobs on the right side. Another knob on the left side is used for fine focusing. The two knobs on the right are modified in this work by placement of two stepper motors on the knobs and making them fixed to a frame structure so that the knobs can be moved easily and the whole support structure moves with the stage. Since the stage is controlled by the system in two directions only, the focus must be adjusted initially by the user manually using the left side knob until a clear vision of the tissue slide is reached. The two stepper motors are driven by standard driver units and are controlled through an Arduino board. Slide image capture is done by a digital camera fitted with an Amscope adapter so that it could be attached to microscope's eyepiece. The camera is interfaced to the PC using USB link and provides Continuous Video when the scanning starts. Although, the same camera can be used for taking still images rather than video, the mechanical delays in stopping the scanner, shutter operation, and image storage rendered this method less practical than using videos. The high level diagram for the system is shown in Fig. 1. After obtaining the video frames, the designed image stitching (IS) algorithm is applied on them. The process of IS involves a series of steps which were applied on the consecutive images, such that one of the image is taken as a reference image (RI) whereas the other one is termed as the current image (CI). The resultant stitched image will be RI for the next consecutive image and then the whole stitching process is applied. The process remain continue for each set until a final stitched image has been obtained from them. Simulation Results In order to perform autonomous clinical analysis on the slide images, it is highly desirable to visualize all slide together (as WSI) especially when the shape and size of the particle is of great importance. The designed algorithm has been applied to Various Images (Frames) acquired from the video of the slide scan and the resultant overall WSI is shown in Fig. 2. Note that the black region shown in the Fig. 2 is produced due to the over-done y-displacement. As can be seen, the stitching is done quite smoothly in spite of the motorized shifts in the scan. In order to show the capability of alignment, the y- axis displacement was over-done by slipping more steps through the worm gear. The algorithm was able to stitch the x segments separately and the y-axis was stitched subsequently. In order to quantify the performance of the presented algorithm, another test was performed using one of the colorectal cancer image from Glas Database. One full image (401x521) was divide into 36 sub-images with 25% overlap in rows and columns between the adjacent sub images. After stitching, the resultant and the original images were compared to highlight the errors as shown in Fig. 3. The grayscale values of the error image were summed together to obtain the total error gray values (TE). This number was divided by the total number of pixels in the image to calculate the percentage error (PE). It was found that the PE for the shown image was 1.16% and was found to be less than 2% for most of the images. Figure 8 shows the test images and results from various steps in the algorithm.
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Nutritional Value of Kid's Meal offered by International Fast Food Restaurants in Qatar
المؤلفون: Abdelhamid KerkadiBackground Global food consumption patterns have dramatically changed in recent years. One common consumption pattern that is shared by many countries is the increasing expenditure on food away from home (FAFH). Convenience and accessibility seems to be the two major reasons why consumers seek for fast food. It is easy to get fast foods anywhere, everywhere and anytime. Consumption of fast-food in the world is becoming an increasingly important component of the food market as more of the working class chooses to dine out rather than prepare meals at home. Despite the importance of the fast-food sector, limited attempts have been made to study the consumption and expenditure behavior of consumers of fast-food. Fast food consumption is increasing among kids, who might lead to many health conditions, one of them is obesity. The nutritional content of kid's meal in Qatar has often been overlooked. The objectives of this study are to assess nutritional value of kid's meal offered by some international fast food restaurants in Qatar and to determine density of international fast food restaurant offering kid's meal by municipality. Methods 6 international fast food restaurants that offer kid's meals were randomly selected. The selected restaurants were McDonald's, Burger king, KFC, Hardee's, Papa john's, and DQ Grill & Chill. We assessed the number of branches of the restaurants using phone applications zomato and talabat. These applications allow the user to know the location and the numbers of branches in different municipalities. We used also the official restaurants websites to collect data of the nutrient content of kids’ meals offered by the 6-international restaurant in Qatar. Also, we used GPS to make sure of the location and the number of these restaurant. All the restaurant offered 4 combinations of kid's meals except Papa John's offered 4 meals. We selected from each restaurant chain 25% of the total branches available in Qatar. During our visit, we asked for nutrition fact of meals offered for kid's. Only McDonald's provide nutrition fact with meals. For other restaurants, we got the information from their official websites or management department. We calculated the density by dividing the number of international fast food over the total number of aged 1-9 years old multiplying by 1000. SPSS version 23 windows was used to analyze the data. We compared the differences in calories, fat, carbohydrate, protein, fiber and sodium content in kid's meals using the one-way ANOVA (at p < 0.005). Results McDonald»s has the highest number of outlets which represent 41 out of 133 international fast food outlets offering kids meals and the DQ grill and chill had the lowest number of outlet which represent 5 out of 133. The average nutrients content of 23 kid»s meal offered by international fast food restaurants in Qatar was 653.30 ± 31.5 calories for calories contents, 21.61 ± 10.24 g for protein content, 28.32 ± 9.07 g for fat content, 84.57 ± 19.22 g for CHO content, 4.40 ± 2.79 g for fiber content and 968 ± 372.31 mg for sodium content. The percentage of covering the RDA calories recommendation of children aged 1-9 years old by 23 kid»s meals offered by six international fast food in Qatar was 47.8 ± 0.02% for calories, 134.6 ± 0.13% for protein, 58.9 ± 0.04% for fat, 63.6 ± 0.03% for CHO, 20.2 ± 0.03% for fiber and 91.4 ± 0.08% for sodium. In general, international fast food kid's meals are rich in carbohydrates, fat, protein, sodium and low in fiber. Conclusion Nowadays children are eating foods prepared outside the home more frequently than ever, improving the nutritional quality of food items offered at fast-food restaurants can contribute to important gains in population health. In this study, we found that fast food meals are nutritionally inadequate and its regular consumption is associated with excess intake of calories, fat, sodium, protein, carbohydrate, and low fiber intake.
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The efficacy of Dapagliozin as a novel oral antihyperglycemic drug in the treatment of patients with type 2 diabetes mellitus
المؤلفون: Rana Moustafa Al AdawiBackground and Aims: Type 2 diabetes mellitus (T2DM) is a prevalent disease affecting millions of patients worldwide. The search for new antidiabetic drugs with innovative mechanisms continues. Dapagliflozin is a second agent in a new class of oral antihyperglycemic drugs; the sodium-glucose co-transporter 2 (SGLT2) inhibitors. Materials and Method: Aim: To evaluate the efficacy of new oral antihyperglycemic drug Dapagliflozin in the treatment of type 2 DM as monotherapy or combination with other hypoglycemic agents. All patients treated with Dapagliflozin in HGH since its introduction as nonformulary medication on 1st April 2013 until 30th April 2015 were included. Data regarding prescribed drugs were obtained from the pharmacy computerized system. Demographic information and laboratory results of patients were obtained from the patient»s electronic system (CERNER). Results: 81 patients were identified to receive Dapagliflazone during the study period, 71 % of them were males, 100 % were Qataries with mean age 57 ± 9 and mean A1c baseline 9 ± 1.4Dapagliflozin as add-on therapy was found to decrease A1c significantly after 6 months by − 0.8 (P = 0.006) and after 12 months by − 1.5 (P = 0.062) The fasting blood was significantly reduced at 6 months and 9 months (P = 0.001, P = 0.03 respectively) There was no significant association between different coadministered antidiabetic medication and reduction in A1c or FBG Conclusion: Dapagliflozin significantly reduced HbA1c level of type 2 diabetic patients in combination of other OHA or insulin within 6 to 12 months of treatment References: 1. Komoroski B, Vachharajani N, Feng Y, Li L, Kornhauser D, Pfister M. Dapagliflozin, a novel, selective SGLT2 inhibitor, improved glycemic control over 2 weeks in patients with type 2 diabetes mellitus. Clin. Pharmacol. Ther. 85(5), 513–519 (2009) 2. Rosenstock J, Vico M, Wei L, Salsali A, List JF. Effects of dapagliflozin, an SGLT2 inhibitor, on HbA1c, body weight, and hypoglycemia risk in patients with type2 diabetes inadequately controlled on pioglitazone monotherapy. Diabetes Care 35, 1473–1478 (2012).
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Wearable RealTime Heart Attack Detection and Warning System to Reduce Car Accidents in Qatar
Introduction Fatal car accidents have become an alarming issue all over the globe. A sudden medical condition such as a heart attack causes medical symptoms that lead a driver to lose consciousness while driving and consequently leads to a crash. Many studies have demonstrated the high correlation between the driver's sudden medical conditions and involving in a car crash [1][2]. Therefore, to reduce car crashes from the driver's sudden illness from heart-attack as well as save the driver's life in a timely manner, in this work, we discuss the development of a portable wearable system that can continuously monitor the driver for any early symptoms of heart attack and inform him before losing conciuous to stop the car as well as inform medical caregivers to save life. Background Myocardial infarction (MI) is the medical term for the medical condition commonly known as a heart attack, a serious medical emergency in which the blood supply to the heart is suddenly blocked, usually by a blood clot, leading to damage heart muscle [3]. A complete blockage of a coronary artery is a ‘STEMI’ heart attack (ST-elevation MI), whereas a partial blockage would be a ‘NSTEMI’ heart attack (a non-ST-elevationMI) [4]. The average, resting heart rhythm has a QRS-complex following a P-wave and followed by a T-wave, as illustrated in Figure 1(a). A STEMI heart attack will cause an elevation in the ST-complex (Figure 1(b)), whereas a NSTEMI heart attack would not signify ST elevation, but nonetheless can cause ST-segment depression or T-wave inversion (Figure 1(c)), which can be detected immediately by a real-time device to save the driver's life. Method The prototype system consists of two subsystems (Figure 2) that communicate wirelessly using Bluetooth low energy (BLE) technology: wearable sensor subsystem, and an intelligent heart attack detection and warning subsystem. Wearable Subsystem: The wearable chest-belt sub-system includes dry electrodes (reference and two electrodes for differential acquisition), analogue front end (AFE), power management module, and RFDuino microcontroller with BLE. This subsystem acquires the ECG signals from human body continuously and sends these raw measurements wirelessly using BLE technology to the intelligent subsystem. Reusable and smaller dimension dry electrodes (Cognionics, Inc) were embedded in a chest belt to be worn by a car driver. AD82832 AFE is an integrated signal conditioning block to extract, amplify (60 dB gain), and filter (0.48-41 Hz) ECG signal in the presence of noisy conditions. Lithium Polymer (LiPo) battery of 3.7 V (1000 mAH) with the Microchip MCP73831 charge controllers, and Texas instruments' TPS61200 voltage regulators to supply 3 V to the wearable system. The miniaturized ARM Cortex M0 RFDuino microcontroller digitizes the signal at 500 Hz sampling rate and transmits the acquired signal through built-in BLE to decision making subsystem. Intelligent Decision-making Subsystem: This subsystem will receive the ECG signals from the wearable subsystem continuously. It is capable of processing, analyzing the received ECG signals, and making the right decision using support vector machine (SVM) algorithm to classify the normal and abnormal ECG signal to detect heart attack symptoms. This subsystem was built around the single board computer, Raspberry Pi 3 (RPi3) along with SIM 908 GSM and GPS module for location information and alerting service. Multi-threaded python code was written for RPi3 to automatically acquire, buffer, baseline correction and digital smoothing and analyse the ECG data. SVM algorithm was implemented in RPi 3 and used for real-time abnormality detection using the trained model and classification was done using LIBSVM, an open source library [5]. 4-fold cross-validation was used to evaluate classification accuracy. SIM908 GSM+GPS shield attached on the RPi3 to provide car location (latitude, longitude) and to connect to the mobile network for generating an automatic call to medical emergency. This subsystem is designed to take power from the car battery using Cigarette Lighter Socket, which powers the system only when the car's engine is ON. To develop the intelligent program for decision-making subsystem, public MIT-BIH ST change database [6] was used to train a SVM model for normal, ST-elevated, and T-inverted ECG-beats with the time domain (TD), frequency domain (FD) and extended time-frequency domain (TFD) features extracted. The TD features mean, variance, skewness, kurtosis, and coefficient of variation and the FD features spectral flux, spectral entropy and spectral flatness were calculated to spot abnormalities in the ECG-beats. Three time-frequency (TF) distributions were also used in this study: Wigner-Ville Distribution (WVD), Spectrogram (SPEC), and Extended Modified B-Distribution (EMBD). Result and Discussion Recorded ECG Traces: It was clearly revealed from Fig. 5 that the ECG signal transmitted using the prototyped system is in clinical grade. Training SVM: Five hundred traces from each patient and total 2500 traces from MIT-BIH database having either normal or abnormal heart rhythm were segmented and averaged for each case (Figure 6 (A, B, & C)). The power spectral of the signal in Figure 6 (D, E & F) shows that the power spectral density peaks appear at different frequencies for normal and abnormal ECG signals. This reflects that the FD feature can help in classifying the ECG signals. However, TD, FD, and TFD features provide an insight on the signal while compensating for the noise or motion artefacts. Classification using SVM: Table 1 below summarizes the accuracy of the prototyped device. EMBD produces higher accuracy in classification of ECG signal. Conclusion This work shows the possibility to detect driver's heart attack reliably using the developed prototype system. SVM machine learning algorithm that was trained with a sufficiently high number of training data can classify STEMI or NSTEMI with approximately 97.4% and 96.3% accuracy respectively when the extended TF features (with EMBD distribution) were used for training and classification. The maximum current drawn by the wearable chest-belt subsystem during continuous acquisition is 9.3 mA, which ensures the life span of a 1000 mAh LiPo battery is 75 hours, once it is fully charged and therefore it can be expected that the device can run longer without requiring recharging daily.
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Efficacy and safety of once daily liraglutideversus twice daily exenatidein type 2diabetic patients in Qatar: an observational study
المؤلفون: Rana Moustafa Al Adawi and Zainab Malik JassimBackground: Type 2 diabetes prevalence is strongly associated with the increase in obesity prevalence. Many of the current diabetic treatments cause further weight gain. Glucagon-like peptide-1 receptor agonists (liraglutide & exenatide) offer advantages of either keeping weight stable or even reducing weight while achieving good glycemic control. Objectives: To compare the glycemic effect of liraglutide versus exenatide over 26 and 52 weeks in uncontrolled type 2 diabetic patients.Methods: A retrospective observation study. Patients with type 2 diabetes who took liraglutide (1.8 mg subcutaneous [SC] once daily) or exenatide (10 mcg SC twice daily) for at least 1 year in addition to their anti-diabetic medications were eligible. For each patient, the following data were collected: HbA1C, fasting plasmaglucose, body weight, blood pressure, lipid profile, hypoglycemia episodes, kidney and liver function. Patient's medical records (both electronic and paper-based records) were used to collect required data. Data analyzed using descriptive & inferential analyses. The study was undertaken by ZJaspart of Masterin clinical pharmacy at Queen's University Belfast Results: 212 patients were included in the study (114 in exenatide group and 98 in liraglutide group). There were no significant differences in all of the patients’ demographics and characteristics between the two groups (table1). Around 73% of included patients were female and half them were aged between 50–59 years. There was in significant difference in mean HbA1C change between both medications at either 26 or 52 weeks (p = 0.23 and 0.40, respectively) (Fig. 1). Patients achieved HbA1C ≤ 7% were significantly higher in the liraglutide group at week 26 (Fig. 2). Liraglutide reduced the mean fasting plasma glucose more than exenatide did at week 26 ( − 1.099 vs. − 0.122 mmol/L; p = 0.15) and week 52 ( − 1.150 vs. − 0.616 mmol/L; p = 0.52). Both medication sex habited weight losses at 26 and 52 weeks; liraglutide − 1.24, − 2.54 vs. exenatide − 1.63, − 3.7 kg, respectively (figure 3). Although both medications were associated with some benefits in term so flipidprofile and blood pressure at a certain point, neither of them were able to show a significant change from baseline. No patients in either groups reported any GI side effects or episodes of hypoglycemia. There was no statistically significant difference between two groups in regards of liver and kidney functions except serum creatinine elevation in heliraglutide group at 52 weeks (p = 0.001). Conclusion: Exenatide and liraglutide resulted in similar glycemic effects (HbA1C and FPG changes) in patients with type 2 diabetes who were sub-optimally controlled with other anti-diabetic therapy. Weight reduction effectiveness was confirmed for both medications with noreported side effects or hypoglycemic episodes during the treatment perid. Future large scale prospective studies are needed to confirm these results.
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