bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel mechanistic pathway linking diabetes to colorectal cancer: Role of AMPK and mTOR
Authors: Abou Merhi Sarah , Ziyadeh Fuad , jaffa Ayad , Eid Assaad
Published: October 2012

Background and Objectives:
Both diabetes and cancer are prevalent diseases with increasing incidence worldwide and especially in countries that are undergoing rapid industrialization (i.e. Gulf countries). Epidemiological studies provide strong evidence that subjects with diabetes are at a significantly higher risk of developing many forms of cancer and in particular solid tumors including colorectal cancer. While diabetes and cancer share many risk factors, the biological links between the two diseases are poorly characterized. In this study we will determine the role of AMPK and mTOR and their crosstalk with NADPH oxidases in normal and cancerous colon epithelial cells and their response to high glucose (HG), high insulin (HI) and their combination. We will also explore the mechanism by which diabetes accelerates tumor development and tumor burden.

Methods:
Cancer migration, cancer proliferation, cancer invasion, Noxs, fibronectin, AMPK, mTOR proteins expression and ROS production were studied by immunohistochemistry.

Results:
We have evidence that HG or HI induces reactive oxygen species (ROS) production in both normal human epithelial colon cells (NCM356) and human epithelial colon adenocarcinoma cells (CaCo₂). To a greater interest, colon cancer itself is a major source of ROS production. Treating CaCo₂ cancerous cells with either HG or HI inactivates adenine monophosphate kinase (AMPK), up-regulates NADPH oxidases Nox1 and Nox4-induced ROS production, associated with increased fibronectin expression and activates the mTOR pathway. In addition, HG or HI enhance cancer cell migration, proliferation, and invasion. Pharmacologic activation of AMPK by 5-aminoimidazole-4-carboxamide-1-riboside AICAR or inhibition of mTOR by rapamycin restores AMPK phosphorylation/activity, downregulates Nox1, Nox4, and fibronectin expression, increases mTOR phosphorylation/activity, and regulates cell migration, proliferation, and invasion

Conclusion:
Our results may uncover a novel and critical role for AMPK and mTOR in cancer cell proliferation and extracellular matrix accumulation in the diabetic milieu; this pathway is through an oxidative stress-dependant mechanism. Our work will set the stage for additional studies to explore new therapeutic approaches for the treatment of cancer in diabetic patients and maybe to a larger extent treatment of cancer.
Using myeloproliferative neoplasm symptom assessment form (MPN-SAF) to evaluate quality of life of MPN patients in Qatar
Authors: yassin mohamed abdeldaem , Elayoubi Hanadi Rafii , Aldewik Nader Izzaldin
Published: October 2012

Background:
Myeloproliferative neoplasms (MPNs), that is, essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are a group of MPNs that can lead to significant rates of morbidity and mortality among affected patients. Symptomatic burden in MPNs is present in most of MPN patients. We sought to use the broadly applicable instrument MPN symptom assessment form (MPN-SAF) to assess symptoms in MF, ET and PV among populations of Qatar.

Methods:
Using the MF-SAF as a base instrument, we added several key additional symptoms previously identified as present in all subtypes of MPNs including headaches, concentration, dizziness, insomnia, sexual problems and mood changes on a 0 (absent) to 10 (worst-imaginable) scale. The MPN-SAF was administered jointly with the EORTC-QLQ-C30 as the co-validation instrument using prospective cohorts in Qatar.

Results:
MPN-SAF patient data: 123 MPN-SAF surveys were administered (English (45%), Arabic (55%) in 45 ET patients (36.5%); 35 PV patients (28.5%); 15 MF patients (12.2%); 28 MPN unclassified (22.7%); an average of 7.8 years (range 0 - 43 years)) from their MPN diagnosis. Participants were of age range (26 - 58 years) and gender (52% female) characteristic of disease. Prior hemorrhage (10%) and thrombosis (25%) were frequent. 78% of the patients currently receive cytoreductive therapy and 87% received cytoreductive therapy in the past.

Patients and Symptomatic Burden: 19 items assessed in the MPN-SAF demonstrated consistently that the most common symptoms were decreased quality of life (93%), fatigue (84%) and insomnia (65%). The least common symptoms (<50% prevalence) were fevers (15%) and weight loss (10%), although symptoms are present in all 3 MPN subgroups. The majority found the MPN-SAF easy to understand (92%) and "addressed most of my MPN symptoms" (95%).

Comparison to EORTC-QLQ-C30: Strong correlations existed between individual items represented on both the MPN-SAF and the EORTC-QLQC30 including pain, fatigue, appetite and insomnia (all p <0.001). Symptoms characteristic of advanced disease including weight loss, fever, and cough displayed lower Pearson correlations (r= 0.46, -0.08, and 0.38 respectively).

Conclusions:
The MPN-SAF is a comprehensive and reliable instrument which is available in multiple languages (including Arabic and English) to evaluate MPN-associated symptoms.
Consanguinity in Qatar: A unique opportunity for international collaborative research
Authors: Ben-Omran Tawfeg , Lakhani Shenela , Almureikhi Mariam , Ali Rehab , Shahbeck Noora , Nawaz Zafar
Published: October 2012

Consanguinity and endogamy is common in the Middle East resulting in higher frequency of autosomal recessive genetic disorders, in particular private or rare genetic conditions. Most of these diseases are due to homoallelic state of pathogenic variants, a direct consequence of founder effect and increased co-efficient of inbreeding.

Advanced molecular genetic technologies such as next-generation sequencing (NGS) are playing an important role in identifying the genetic basis of rare genetic conditions, specifically when a consanguineous couple has more than one affected child with a rare genetic condition suggestive of autosomal recessive inheritance. The NGS technology is used to sequence the whole genome or whole exome with high accuracy in limited time at a very low cost. There are many platforms available for this technology with slightly different chemistry and variable calling rates.

In general, the Qatari population is a highly endogamous population and largely made up of tribal communities with high prevalence of autosomal recessive disorders. The NGS technology will facilitate a promising outcome for unraveling the genetic aetiology of such inherited conditions. However, this technology requires highly trained laboratory geneticists along with bioinformatics support to develop pipelines for data analysis and interpretation, requiring considerable local and international collaborative interactions.

In this paper, we will share our experience with collaborative research projects funded by Qatar National Research Fund (QNRF) to transfer and develop these genetic technologies in the State of Qatar, for the investigation of inherited monogenic disorders.
The effect of rate dependency on the failure locus of the anterior cruciate ligament
Authors: Orsi Alexander , Vaziri Ashkan , Hamouda Abdel Magid , Goebel Ruben , Nayeb-Hashemi Hamid
Published: October 2012

Background:
Anterior cruciate ligament (ACL) tears are common injuries occurring upwards of 250,000 times annually only in the US. These injuries create an annual billion dollar expense in the US alone. It is important to understand these mechanisms of injury as these injuries continue to be one of the largest problems in orthopedic sports medicine. Improved understanding of the injury mechanisms may improve prevention, rehabilitation and surgical procedures.

Objectives:
To perform a parametric study of knee joint movement to highlight which movement combinations are most detrimental to the ligaments of the knee joint, and also to study the effect of ramping rate on varus and valgus failure angle. The study provides a spectrum of injury propensity based on internal and external femoral rotation and varus or valgus angle as well as showing the effect of ramping rate on the prescribed boundary conditions.

Methods:
Bones and ligaments were digitized from magnetic resonance images (MRI). Bone was modeled as rigid, and a transversely isotropic visco-elastic material was applied to the ligament structures. This study incorporates a novel approach for developing bundle specific prestrain within 3D ligament structures. The bundles were stretched from their zero load lengths to their reference lengths, producing a strain field mimicking the in vivo strain conditions of the ACL at full knee extension. A failure locus was created by performing multiple FE simulations of knee joint motion combinations until ACL failure at different ramping rates to investigate the effect of rate dependency on the valgus and varus failure angle of the ACL.

Results:
Loading rate had negligible effect on the valgus or varus ACL failure angle. External femoral rotation scenarios were more susceptible to ligament failure than internal femoral rotation. The postero-lateral bundle showed more injury susceptibility compared to the anteromedial bundle. Varus simulations showed less angle needed for failure when compared to valgus simulations.

Conclusions:
These results have various clinical applications. In sports where ACL injuries are prevalent, training programs can be adapted to address the avoidance of harmful knee orientations.
Sociodemographic determinants of neonatal mortality in the State of Qatar: A PEARL study analysis
Authors: Rahman Sajjad ur , Nimeri Nuha , El Tinay Sarrah , Al Rifai Hilal , El Ansari Walid , Tahir Mohammad
Published: October 2012

Background and Objectives:
The State of Qatar has achieved maternal, neonatal and perinatal survival rates which are comparable to many high income countries, both from the West and East. Our study aims to analyze sociodemographic, economic and cultural determinants of Qatar's neonatal mortality rate (NMR) during 2011.

Methodology:
PEARL study (Perinatal Neonatal Outcomes Research Study in the Arabian Gulf), a joint collaborative research project between Hamad Medical Corporation (HMC), Qatar, and University of Gloucestershire, United Kingdom, is Qatar's prospective national perinatal epidemiological study funded by Qatar National Research Fund. The study is quantifying maternal, neonatal and perinatal mortality, morbidities and their correlates by establishing a national neonatal perinatal registry for Qatar called Q-Peri-Reg. Data on live births and neonatal mortality was collected from all public and private maternity facilities in Qatar during 2011. Data on sociodemographic, economic and cultural determinants was ascertained by direct interviews from the mothers using predesigned performas. Univariate and multivariate regression analysis was done using Epi Info and SPSS-20.

Results:
Qatar's NMR during 2011 was 4.9. Babies born to mothers with no or less than secondary level of education were twice at risk of death as compared to mothers with secondary or more level of education (RR 2.08, 95% CI 1.23-3.53, p= 0.009). The rate of maternal literacy was 90%. Nationality, gender, consanguinity, maternal occupation, family income and status, type and ownership of housing did not have any statistically significant correlation with the risk of neonatal mortality (Table1).

Conclusion:
High level of maternal literacy in Qatar appears to have contributed significantly to its improved neonatal survival rates. The outcome is independent of nationality, gender, social, economic and living status which supports the notion of an equitable health system in Qatar.
Posaconazole a prophylactic therapy in hematological cancer patients: Drug use evaluation study
Authors: Hamdy Dalia , El-Geed Hager , El-Salem Samah , Zaidan Manal
Published: October 2012

Background and Objectives:
Posaconazole (PSZ), is an antifungal prophylactic therapy that is used in hematologic cancer patients. It is approved for prophylaxis in hematologic cancer patients ≥13 years in USA, Canada, Australia, and ≥18 years in the European Union. In 2010, PSZ was added to the formulary of Al-Amal Hospital, the only adult cancer hospital in Qatar. The objective of this study is to conduct a drug use evaluation (DUE) study of posaconazole at Al-Amal Hospital.

Methods:
A retrospective, single centered, observational DUE study was conducted to include a convenient sample of hematologic cancer patients who used PSZ prophylactically during the year 2010. All patients, thirty-one, who received PSZ in 2010 were nominated of which 20 patients' profiles were reviewed, data were collected into a pre-prepared collection sheet and descriptive analysis was performed.

Results:
In Qatar, PSZ was used prophylactically in hematologic cancer patients >15 years with febrile and afebrile neutropenia. It is also planned to be used prophylactically for the upcoming bone marrow transplantation unit patients. All the 20 patients, 17 males and 3 females, received the PSZ for prophylaxis and were compliant. More than 50% of patients received proton pump inhibitors concurrently with posaconazole. Only 1 case had a recorded recommendation regarding the administration of PSZ with food. Five patients received vincristine-based chemotherapy protocol, one of which received it concurrently with PSZ for two cycles and developed seizure. Two patients developed mild breakthrough fungal infection, oral thrush, while on PSZ prophylactically.

Conclusion:
The PSZ regulations in Qatar are similar to the worldwide recommendations. The PSZ practice in Al-Amal hospital abides by the regulations. However, three points need to be addressed: PSZ has low bioavailability that can be enhanced by taking it with meals and by dividing the total daily dose. PSZ co-administration with proton pump inhibitors should be stopped as it may result in PSZ sub-therapeutic levels. Possible serious PSZ drug-drug interactions, seizures, in adult hematologic cancer patients should be highlighted and carefully monitored.
Novel oral formulations of metformin in semi-solid matrices: Design, characterization and in vitro dissolution testing
Authors: Ali-Adib Sandi , Abuhelwa Ahmad , Younes Husam M
Published: October 2012

Objectives:
To formulate and evaluate oral dosage forms of metformin hydrochloride (MH) having sustained-release properties that would also increase MH bioavailability and address the shortcomings in the currently marketed sustained-release tablets.

Methods:
MH micronized powder was dispersed in molten polymeric matrices composed of Gelucire® 50/13 and various proportions of high molecular weight hydrophilic polymers, hydrophobic oily semisolid excipients, and mucoadhesive polymeric materials. The MH loaded matrices were filled in hard gelatin capsules (HGC) each containing 500 mg MH and were subsequently characterized using differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis. The prepared HGC were subjected to content uniformity and in vitro dissolution testing according to the USP-35 compendium requirements. The dissolution data were compared to instant and sustained-release marketed tablets. The effect of incorporating various proportions of the semisolid excipients on MH dissolution release rate, were also investigated.

Results:
MH content of the prepared HGC ranged between 96 to 103%. All the prepared semisolid filled HGC resulted in extended-release profiles of MH that lasted between 5 to 11 hours and demonstrated a release pattern which typically follows the release from mixes of triglycerides with polyethylene glycol esters of fatty acids. The incorporation of mucoadhesive excipients like carbomer to the Gelucire® 50/13-MH semisolid matrices extended the release of MH from 5 hours initially to 9 hours as a result of the formation of a gel layer around the matrix. However, the incorporation of different hydrophilic excipients like PEG35000 and Gelucire® 44/14 along with the mucoadhesive excipients sustained the release of MH up to 11 hours. XRD analysis of the MH prepared matrices demonstrated minor changes in the crystalline nature of MH. Depending on the loading ratios and the nature of the semisolid matrices used, DSC analysis revealed the changes in MH crystallinity to be from 100 to 23%.

Conclusion:
HGC formulated using semisolid matrices showed promising results in extending the release of MH. However, bioavailability studies to test the ability of such Gelucire based HGC of MH to improve its bioavailability and in vivo residence times are future plans.
Identification of novel genes causing autosomal recessive disorders in Qatari population using whole exome sequencing
Authors: Fahiminiya Somayyeh , Almuriekhi Mariam , Nawaz Zafar , Staffa Alfredo , Majewski Jacek , Ben-Omran Tawfeg
Published: October 2012

Background
Consanguinity and endogamy are common in the Middle East, resulting in a higher frequency of autosomal recessive (AR) disorders. This consanguinity facilitates discovery of disease causative genes particularly after introduction of the new techniques such as Whole Exome Sequencing (WES). In order to reduce the overall socio-economic burden of such diseases, the development of diagnostic tools and prevention strategies must be a priority. To achieve these goals, the causal genes underlying human genetic diseases should be first discovered. The goal of this study is to identify novel genes causing AR diseases in Qatari population using WES.

Methods
Genomic DNAs were captured with the Illumina TruSeq library and sequenced with Illumina HiSeq2000. The reads were aligned to the reference genome using BWA. Variants calling and annotation were performed by SAMtools and ANNOVAR, respectively. Novel variants were defined as those having an allele frequency <0.05 in the 1000 Genomes database and predicted to be nonsynonymous substitutions.

Results
WES was applied on affected individuals of 3 consanguineous families with Mental Retardation (MR: 2 siblings), Peripheral Neuropathy (PN: 2 siblings) and Eye Anomaly (EA: 1 male). The mode of inheritance was assumed to be AR in MR and PN families. This led to identification of 3 and 4 homozygous candidate variants, shared by two siblings, respectively. The mode of inheritance in EA was considered to be AR and/or X-linked that led to the identification of 26 autosomal homozygous and 6 X-linked genes. The function of one of the genes on X-chromosome was related to the patient phenotype.

Conclusions
These preliminary interesting results highlight the power of WES, to identify potential candidate genes for AR disorders. The identified genes will be considered for functional follow-up investigation and further characterization. However, our results also highlight that the large number of population-specific variants - which may be common polymorphisms in Qatar but are so far absent from public databases - make diagnosis and discovery more difficult than in well-studied Caucasian populations. We urge genetics researchers in Qatar to actively participate in the creation of a local variant database, which will greatly facilitate such future studies.
Hydrogen peroxide induces stress granule formation independent of eukaryotic initiation factor 2α phosphorylation
Authors: Fujimura Ken , Scharengella Daniel , Ivanova Victoria , Ivanov Pavel , Anderson Paul , Emara Mohamed
Published: October 2012

Background and Objectives:
In cells exposed to environmental stress, inhibition of translation initiation conserves energy for the repair of cellular damage. Untranslated mRNAs that accumulate in these cells move to discrete cytoplasmic foci known as stress granules (SGs). The assembly of SGs helps cells to survive under adverse environmental conditions. SGs are formed as a consequence of eIF2α phosphorylation that inhibits translation initiation. However, this is not the sole mechanism by which SGs are assembled. Some compounds inhibit translation and induce SG formation via the interaction with eIF4A. During oxidative stress conditions, reactive oxygen species (ROS) levels increase dramatically causing a significant alteration in cell metabolism including protein synthesis. The most stable form of the ROS is hydrogen peroxide (H2O2), which was found to inhibit protein synthesis in different types of cells. The objective of our study is to analyze the mechanism by which H2O2-induced oxidative stress inhibits translation initiation and induces SG assembly in mammalian cells.

Methods:
Cells were treated with different concentrations of H2O2 and then fixed, stained with SG markers, and visualized using fluorescence microscopy to quantify SGs. To test the effect of oxidative stress treatment on eIF4F complex formation we pulled down the eIF4F complex from lysates of SA or H2O2- treated U2OS cells using m7GTP-Sepharose.

Results:
H2O2 inhibits translation and induces the assembly of SGs. The assembly of H2O2-induced SGs is independent of the phosphorylation of eIF2α, a major trigger of SG assembly, but requires remodeling of the cap-binding eIF4F complex. Moreover, H2O2-induced SGs are compositionally distinct from canonical SGs, and targeted knockdown of eIF4E, a protein required for canonical translation initiation, inhibits H2O2-induced SG assembly.

Conclusions:
In conclusion, our data suggest that mammalian cells can assemble different types of SGs utilizing different mechanisms. These different routes of assembly are stress-specific and dictate recruitment of selective SG constituents. In analogy to amino acid starvation-induced SGs that selectively sequester mRNAs bearing 5'-terminal oligopyrimidine tracts, we propose that different classes of SGs selectively recruit specific mRNAs from translating ribosomes. In turn, this selective mRNA re-localization causes stress-specific changes in protein translation allowing adaptation to stress conditions.
HIV prevention randomized clinical trials: quantitative and analytical insights on the failure to measure efficacy
Authors: Cuadros Diego , Abu-Raddad Laith , Garcia-Ramos Gisela
Published: October 2012

Background & Objectives:
Despite the solid foundation on epidemiological evidence and basic science research, nearly 90% of the randomized controlled trials (RCT) designed to measure the efficacy of interventions on HIV incidence failed to measure a statistically significant efficacy against HIV incidence. Here, we propose the use of computer simulations to control trials as a useful tool to overcome the difficulty of effect size estimation and outcome interpretation derived from HIV intervention RCTs.

Methods:
We simulated the Partners in Prevention HSV/HIV transmission study recently conducted to test the efficacy of herpes simplex virus type 2 (HSV-2) suppressive therapy by acyclovir in reducing HIV transmission. We also simulated different variations of this trial, and the Rakai male circumcision trial. We developed individual-based Monte-Carlo models parameterized by the data of these RCTs and simulated the RCTs 1000 times. To measure the efficacy of the intervention, we conducted a log-rank survival analysis for each RCT realization and estimated the statistical power as the fraction of realizations that rejected the null hypothesis.

Results:
Our analyses indicated that the partners in prevention RCT had only 14% likelihood to observe a statistically significant efficacy for the intervention. In contrast, a different and more potent regimen for HSV-2 suppression had 87% chance of observing a statistically significant efficacy. For the Rakai male circumcision trial simulation, 94% of the RCT realizations showed statistically significant efficacy for the intervention.

Conclusions:
The simulations indicate that several unexpected odds have colluded to undermine the statistical power of the partners in prevention study, and therefore it would be premature to discredit the concept of acyclovir therapy for HIV prevention based on the outcome of the partners in prevention trial. Our study highlights how in silico simulations of RCTs can provide powerful tools for optimizing the design of RCTs and predicting their outcome. Observational and biological evidence summarized in computer simulations could help us on the estimation of effect size ranges and a better understanding of the system, which might provide a powerful tool to enhance the success of any HIV intervention RCT.
Evaluation of glycemic abnormalities in patients with Beta Thalassemia major using continous glucose monitoring system (CGMS) and oral glucose tolerance test (OGTT): A pilot study
Authors: Yassin Mohamed Abdeldaem , Soliman Ashraf Tawfiq , Alawwa Ahmed Said
Published: October 2012

Introduction:
Both insulin deficiency and insulin resistance are reported in patients with β thalassemia major (BTM). The use of CGMS among the different methods for early detection of glycaemic abnormalities has not been studied thorough.

The aims of this study are: 1. to detect glycemic abnormalities in young adults with BTM using fasting blood glucose (FBG), (OGTT), 72-h continuous glucose concentration by CGMS, and serum insulin and C-peptide concentrations; 2. To compare the results of these two methods in detecting glycemic abnormalities in these patients; and 3. To calculate (HOMA), and (QUICKI) in these patients. In order to evaluate whether glycemic abnormalities are due to insulin deficiency and/or resistance.

Materials and methods:
Randomly selected young adults (n = 14) with BTM . All patients were investigated using (OGTT) 75 gram of glucose and 72-h by CGMS. Fasting serum insulin and C-peptide concentrations were measured and HOMA-B, HOMA-IR were calculated accordingly.

Results:
Using OGTT, 5 patients had impaired fasting glucose (IFG) (Fasting BG from 5.6 to 6.9 mmol/L). Two of them had impaired glucose tolerance IGT (BG from 7.8 and < 11.1 mmol/L) and one had BG = 16.2 mmol/L after 2-hrs (diabetic). Using CGMS in addition to the glucose data measured by glucometer (3-5 times/ day), 6 patients had IFG. The maximum (postprandial) BG recorded exceeded 11.1 mmol/L in 4 patients (28.5%) (Diabetics) and was > 7.8 but < 11.1 mmol/L in 8 patients (57%) (IGT).

The mean values of HOMA and QUICKI in patients with BTM were < 2.6 (1.6± 0.8) and > 0.33 (0.36±0.03) respectively ruling out significant insulin resistance in these adolescents. There was a significant negative correlation between the β-cell function (B%) on the one hand and the fasting and the 2-h BG (r= -0.6, and - 0.48, P< 0.01 respectively) on the other hand. Ferritin concentrations were negatively correlated with the β-cell function (r= -0.41, P< 0.01).

Conclusion:
CGMS has proved to be superior to OGTT for the diagnosis of glycemic abnormalities in adult patients with BTM. In our patients, defective β-cell function rather than insulin resistance appeared to be the cause for these abnormalities.
Endothelial cells provide a niche for placental hematopoietic stem cell expansion
Authors: Raynaud Christophe , Rafii Arash
Published: October 2012

Umbilical cord blood (UCB) is an attractive source of hematopoietic stem cells (HSCs). However, the number of HSCs in UBC remains limited and the attempts to amplify them in-vitro remain of poor efficiency. Several publications document amplification of HSC/progenitors with endothelial or mesenchymal cells, but the lack of homogeneity in culture conditions or HSC qualification impairs direct comparison of these results. Therefore, we compared the possible HSCs amplification using placental mesenchymal progenitors and Akt-activated umbilical vein endothelial cells. After HSCs isolation from UCB (defined as Lin-CD45-CD34+CD38-CD90+) on confluent feeder layer, the number of total cells and HSCs were monitored over 21 days. We demonstrate important cellular expansion on both niches. Most of the expanded cells were differentiated when characterized by flow cytometry. Only endothelial cells could trigger HSCs amplification with a pick at 14 days. Those amplified HSCs were able to differentiate in all cell lineages as attested by colony forming assays. Mesenchymal progenitors mainly triggered the amplification of CD38+ cells previously defined as precursors. A competitive assay demonstrated that HSCs had an in-vitro preference to interact with endothelial cells. Cytokines and transcriptomic analysis of our feeders indicate the mechanisms involved in HSC amplification and differentiation in both cases.
Determination of titanium and copper by ICP-MS in rat tissues after oral administration of nanoparticles
Authors: Amr Mohamed A. , Aljufairi Najat
Published: October 2012

In this study, the high sensitive ICP-MS was employed to detect the contents of titanium and copper in liver, lung, spleen, kidney, heart, testis, brain and blood after administering an acute dose of different nano particle sizes of titanium and copper to rats by a syringe via gastrointestinal tract. In coupling with pathological examinations, the target organs of nano- and micro-copper were successfully determined. Biodistribution experiment showed that TiO2 mainly retained in the liver, spleen, kidneys, and lung tissues, which indicated that TiO2 particles could be transported to other tissues and organs after uptake by gastrointestinal tract. Moreover, the target organs of copper nano particles of different sizes after administrating a dose of 100 mg/kg were kidney, liver and blood. Liver is the main damaged organ.
Adipokines as mediators of components of metabolic syndrome in a Qatari population
Authors: Elrayess Mohamed Aghar , Al-Jaber Mashael , Bakhamis Aysha , Muhammad Ali Ameena , Orie Nelson N , Rida Samer , Al-Emadi Mohamed , Mohamed-Ali Vidya , Alsayrafi Muhammad
Published: October 2012

Background and Objectives:
There is a high prevalence of obesity and its co-morbidities within the Arab population, especially in Qatar. Furthermore, the younger age of onset of obesity and its preponderance amongst females have seen an increase in type 2 diabetes and cardiovascular disease in this cohort. Adipose tissue dysfunction preceding frank obesity may underlie the increased risk of metabolic syndrome (MeS). Therefore aims of this study were to characterize the relationship between components of MeS and adipokines in a Qatari population.

Methods:
Non-diabetic subjects were recruited from the general Qatari population and patients awaiting weight reduction surgery (Al-Emadi Hospital). Lipid profiling and liver function were determined by conventional techniques (HMC). Insulin resistance was measured by HOMA. Adipokines were measured by ELISA.

Results:
In the whole study population (n=56, 13 males/43 females, 30.5+/-7.5 years old, BMI of 37.5+/-11kg/m-2) significant positive correlations between plasma leptin and BMI were confirmed. However, after controlling for BMI, partial correlations showed that leptin was associated negatively with all measures of blood pressure (all p≤0.01), triglycerides, total- and LDL-cholesterol (all p≤0.01), with liver enzymes (SGPT, AST and Billirubin, p=0.009, p≤0.01 and p=0.02 respectively), and positively with HDL cholesterol (p=0.05). Furthermore, leptin, was also negatively correlated with fasting blood glucose and HOMA (p=0.03 and p=0.01 respectively). In order to investigate this further, the population was dichotomized into age-matched normal weight (n=14) and obese (n=42) sub-groups. The obese group had significantly higher SBP (p=0.006), triglycerides (p=0.03), leptin (p≤0.001) and lower HDL (p≤0.001). Obesity was also associated with deteriorating liver functions manifested as elevation in SGPT (p =0.02), ALP (p= 0.01) and AST (p =0.02).

Conclusions:
Leptin was elevated in obesity. After correcting for BMI, an inverse relationship between leptin and risk factors for MeS was apparent, suggesting a protective role for leptin in this population, perhaps through its vasodilatory capability. However, when dichotomized into lean and obese groups, chronic elevation in leptin appeared to be associated with increased risk of MeS and deterioration of liver function, as previously described. These novel data are currently being confirmed in a larger ethnicity matched cohort.
Inhibition of NFκB signaling in calreticulin deficient cells
Authors: Massaeli Hamid , Viswanathan Divya , Liberska Aleksandra , AlDabhani Kawathar , Mesaeli Nasrin
Published: October 2012

Calreticulin (CRT) is an endoplasmic reticulum (ER) Ca²+ binding chaperone, which regulates many of cellular processes. Previous work from our lab showed loss of CRT leads to increased resistance to apoptosis. We also showed loss of CRT leads to increased AKT phosphorylation and activation of the proteosome activity. Thus we hypothesized that in the absence of CRT function, NFκB signaling is activated leading to enhanced resistance to apoptosis of these cells.

Wild type and CRT knockout mouse embryonic fibroblast were used to examine changes in the NFκB signaling pathway. Reporter gene assays showed a significant reduction in the basal NFκB transcriptional activity. Activation of NFκB with lipopolysaccharide increased the transcriptional activity of NFκB in both the cells, however, the transcriptional activity of NFκB was still significantly lower in the CRT deficient cells as compared to the wild type cells. Our immunocytochemical staining showed a delay in the translocation of NFκB p65 to the nucleus of CRT deficient cells after lipopolysaccharide treatment. We also observed an increase in the level of IκB and phospho-IκB accumulation in CRT deficient cells after lipopolysaccharide treatment.

We conclude that in the absence of CRT NFκB signaling is inhibited due to decreased IκB degradation and decreased NFκB p65 nuclear translocation.
SID-MRM-MS enabled verification of biomarkers of type 2 diabetes in a Qatari population
Authors: Kaur Prabhjit , Rizk Nasser M , Younes Noura , Zirie Mahmoud , Cheema Amrita K
Published: October 2012

Background and Objectives:
Recent technological advancements in liquid chromatography coupled with high resolution mass spectrometry have facilitated clinical biomarker discovery, verification and validation. Targeted metabolic profiling refers to the precise quantitative measurements of metabolites for validation of markers identified via untargeted metabolomics. Specifically, multiple reaction monitoring mass spectrometry has enabled the reliable quantification of biomarkers in hundreds of samples, in a multiplexed manner.

Methods:
In this clinical study we have employed SID-MRM-MS (stable isotope dilution - multiple reaction monitoring - mass spectrometry) to quantify different classes of endogenous metabolites including intermediates of TCA cycle and lipids, on a triple quadrupole mass spectrometer. NPRP funded project enabled us to recruit a total of 169 controls and T2DM (type 2 diabetes mellitus) patients at the Hamad Medical Corporation in Doha, Qatar. Based on the discovery mode metabolomics profiling experiments, ten target molecules were chosen for biomarker validation using a cohort of 72 (control and diabetic) urine and plasma samples spiked with a known concentration of stable isotope labeled standard for each metabolite. The normalized peak area ratios were used to calculate the levels of deregulated metabolites in the T2DM cohort. We also performed extensive quality control experiments to check for retention time variation, matrix effects and metabolite degradation during sample processing. Statistical analysis was performed using GraphPad Prism (v5.0). ROC curves and interactive plots with a stringency cut-off of P ≤0.05 were plotted to test biomarker specificity and sensitivity. The cut-off values were selected to maximize the Youden index.

Results:
Statistically significant downregulation of succinate, xanthurenic acid, α-ketoglutaric acid and kynurenic acid were observed in the T2DM group while the concentrations of serotonin, PG (18:0/18:1), PC, sphingosine-1-phosphate and pyruvate were determined to be significantly higher in the diabetic group. The OPLS-DA model for the target metabolites had two orthogonal components and the R2 and Q2 were 0.88 and 0.87 respectively.

Conclusions
Our results underscore the clinical and translational utility of the MRM-MS approach. Further validation and characterization with larger cohorts, is likely to provide valuable insights into clinical potential of these markers and their correlation with T2DM associated complications.
Relationships between anthropometric factors and repeated-sprint ability in the Qatar national soccer team
Authors: Brocherie Franck , Millet Gregoire P. , Forchino Fabricio , Dos Santos Gilvan A. , Eirale Cristiano , Di Salvo Valter , Girard Olivier
Published: October 2012

Background & Objectives:
Muscle mass is a major determinant of power development during maximal sprinting. The ability to recover and subsequently reproduce high-intensity efforts (termed repeated-sprint ability, RSA) is closely related to match-performance in soccer. The aim of this study is to assess any relationship between anthropometric parameters and RSA performance in a national soccer team in the Middle East.

Method:
Sixteen members of the senior male Qatar national soccer team performed six 35-m maximal running sprints on grass departing every 10-second. Sprint times, acceleration (Accbest and Accmean), velocity and peak (PP) and mean (MP) power were calculated. Power results were also adjusted to body mass. To assess RSA, total time and sprint decrement (Sdec) score were calculated. Anthropometric measures (e.g. breadths, girths, skinfolds) and derived factors (e.g. body composition, proportionality) were assessed according to the standard of the International Society for the Advancement of Kinanthropometry. Pearson's product-moment correlations were conducted.

Results:
Significant (p<0.05) relationships occurred between muscle-to-bone ratio and all RSA variables (r < -0.53 for sprint times and all r > 0.51 for Accmean, velocity and power scores) with the exception of Accbest and Sdec. Muscle index, cross-sectional area for mid-thigh and calf muscle groups were only correlated (p<0.05) with PP (r = 0.70, 0.73 and 0.60, respectively) and MP (r = 0.63, 0.73 and 0.62 respectively). The sum of 6 skinfolds and adipose index were positively correlated with Sdec (r = 0.68 and 0.55, respectively; p < 0.05).

Conclusion:
In the Qatar national soccer team players' RSA is associated with a high muscular profile and a low adiposity. Such observation would be of benefit with the purpose of providing training and nutritional recommendations to improve match-related performance in soccer.
Using lean principles and process analysis techniques to reduce congestion in out patient departments
Authors: Mutlu Fatih , Pokharel Shaligram , Gamal Noura , Almadhoun Fatima , Diab Dima , Fadel Zina , Al-Sarraj Lama
Published: October 2012

Background and Objectives: Congestion in outpatient departments (OPD) in Qatar's public hospital system is a major problem due to the demographics of the country. Despite the congestion in the general registration and assessment areas, the utilization of doctors' time is considerably low. This paradigm is propagated by (i) the inefficiencies in the appointment system, (ii) the allocation of the resources in the service design, and (iii) behavior patterns of the patients.
Methods: We investigated the problem through a case study in a public hospital. First, through a careful walk-through of the patients' flow process, we identified the disruptions in the patient flows using lean principles. Simultaneously, through extensive data collection, we measured the patient flow times and resource utilization, and classified the value added- and non-value added times for the patients. Based on the observations and data collected, we propose changes for the appointment systems, patients' flow process, and allocation of resources. We benchmark the impact of our suggestions through simulation.
Results: The improved solutions reduce the patient flow times by 30%.
Conclusions: The patients' flow experience in public hospitals' OPDs can be significantly improved through better design of the appointment system and by eliminating wasted time in the patient flow process without investing in more resources.
A flexible and concurrent MapReduce programming model for shared-data applications
Authors: Zhang Fan , Malluhi Qutaibah M
Published: October 2012

The rapid growth of large data processing has meant the implementation of the MapReduce programming model as a widely accepted solution. The simple map and reduce stages have introduced convenience to programmers in order that they may quickly compose and design complex solutions for large-scale problems.

Due to the ever-increasing complexity of execution logic in real-life applications, more and more MapReduce applications involve multiple correlated jobs encapsulated and executed according to a defined order. For example, a PageRank job involves two iterative MapReduce sub-jobs; the first job joins the rank and linkage table and the second one calculates the aggregated rank of each URL. Two non-iterative MapReduce sub-jobs for counting out-going URLs and assigning initial ranks are also included in the PageRank job.

Besides this, MapReduce programming model lacks built-in support and optimization when the input data are shared. The performance will benefit when the shared and frequently accessed files are read from local instead of from distributed file system.

This paper presents Concurrent MapReduce; a new programming model built on top of MapReduce while maintaining optimization and scheduling for big data applications that are composed of large number of shared data items. Concurrent MapReduce has three major characteristics:

(1) Unlike traditional homogeneous map and reduce functions, it provides a flexible framework, which supports and manages multiple yet heterogeneous map and reduce functions. In other words, programmers are able to write many different map and reduce functions in a MapReduce job.

(2) It launches multiple jobs in a task-level concurrency and a job-level concurrency manner. For job-level concurrency, the framework manages the shared data by replicating them from HDFS to the local file system to ensure data locality. For task-level concurrency, it is the programmers' responsibility to define the data to be shared.

(3) We have evaluated the framework using two benchmarks: Single Source Shortest Path and String Matching. Results have demonstrated up to 4X performance speedup compared to traditional non-concurrent MapReduce.
Distributed load balancing through a biomimetic self organisation framework
Authors: Imran Ali , Yaacoub Elias , Abu-Dayya Adnan
Published: October 2012

In wireless cellular systems, uneven traffic load among the cells increases call blocking rates in some cells and causes low resource utilisation in others and thus degrades user satisfaction and overall performance of the cellular system. Various centralised or semi-centralised Load Balancing (LB) schemes have been proposed to cope with this time persistent problem, however, a fully distributed Self Organising (SO) LB solution is still needed for the future cellular networks. To this end, we present a novel distributed LB solution based on an analytical framework developed on the principles of nature-inspired SO systems. A novel concept of super-cell is proposed to decompose the problem of "system-wide blocking minimization" into the local sub-problems in order to enable a SO distributed solution. Performance of the proposed solution is evaluated through system level simulations for both macro cell and femto cell based systems. Numerical results show that the proposed solution can reduce the blocking in the system close to an Ideal Central Control (ICC) based LB solution. The added advantage of the proposed solution is that it does not require heavy signalling overheads.
Identifying, implementing and recognizing Arabic accents in facial expressions for a cross-cultural robot
Authors: Alzeyara Amna , Sakr Majd , Ziadee Micheline
Published: October 2012

In this work we attempt to understand the visual accents in Arabic facial expressions and create culture-specific facial expressions for a female multi-lingual, cross-cultural robot. This study will enable the investigation of the effect of creating such expressions on the quality of the human-robot interaction.

Our work is twofold: we first identify the existence of accent variation in facial expressions across cultures, then we validate human recognition of these accents. Facial expressions embody culture and are crucial for effective communication; hence they play an important role in multi-lingual, cross-cultural human-robot interaction. Elfenbein and Ambady found that there are different accents in facial expressions, which are culture-specific, and that the differences in expressions between cultures can create misunderstandings [Elfenbein and Ambady, 2003]. Several studies compared American expressions with expressions from other cultures but none of them included Arabic facial expressions.

There is no existing database for Arabic facial expressions. Consequently, we recorded videos of young Arab women narrating stories that express six emotions: happiness, sadness, surprise, fear, disgust, and disappointment. These videos were analyzed to extract Arabic accents in facial expressions. The expressions were then implemented on a 3D face model using the Facial Action Coding System (FACS). To evaluate the expressions we conducted a web-based, human-subject experiment directed at students and staff at Carnegie Mellon University in Qatar. Thirty-four participants were asked to choose the appropriate emotion for each expression and rate, on a ten-level Likert scale, the accuracy with which the expression represents the emotion. The cultural affiliation of the participants was recorded.

Preliminary results show that Arabs are more likely to recognize the Arabic facial expressions over non-Arabs. To further support this conclusion the survey will be redistributed to a larger number of subjects from different cultural backgrounds and from different geographical areas.
RFID distributed antenna systems for intelligent airport applications
Authors: Bekkali Abdelmoula , Kadri Abdullah
Published: October 2012

Recent developments in radio frequency identification (RFID) technology have enabled the aviation industry to benefit from its huge potential to solve issues related to baggage mishandling and to improve passenger journeys. The International Air Transport Association (IATA) estimates that more than $733 million savings by airlines alone can be realized through RFID adoption when fully implemented in the top 200 airports. Despite the obvious benefits of RFID technology in airport industry service applications, potential implementation obstacles and technical deployment challenges have to be overcome for effective, low cost and reliable passive RFID-based baggage handling and passenger asset monitoring systems. In the existing RFID system, where the RFID readers are usually placed on the conveyors, the reliable read range is often limited to a few meters. Location is then inferred from the last portal a tag is read at. In addition, the RFID tags reading accuracy varies from 97-99% in most implemented systems. This work aims at improving airport efficiency and security through real-time locating and tracking of both passengers and baggage within airport facilities. We propose to apply the concept of optical distributed antenna systems (DAS) to RFID, to develop an intelligent, adaptive, and self-organizing passive RFID real-time locating system (RTLS), suitable for deployment in airports. This system can provide reliable coverage over a wide area using only few RFID antennas. Our system will have the following characteristics and advantages. Firstly, the RFID DAS system will allow users to rapidly identify all tags and collect information with a reading tag accuracy of 100% compared to ~90-99% for the existing implemented RFID system. And thus, it can eliminate the error of manual operation. Secondly, the interrogation area or the reader coverage is greatly expanded up to 20 meters compared to 3 meters range of the existing system. Thirdly, in addition to baggage handling, the system can also track passengers and airport staff and devices. Finally, this system will provide a glimpse of the great potential returns that will support the smart airport vision.