bluuebunny/crossref_metadata_2025 huggingface dataset:
Gamification of exercise and its application for fall prevention among patients with diabetes and peripheral neuropathy
Authors: Najafi Bijan
Published: November 2013

Background: Individuals with diabetic peripheral neuropathy (DPN) frequently suffer from concomitant impaired proprioception and postural instability. Conventional exercise training has been demonstrated effective in improving balance; however these exercises are often repetitive, causing patients to lose interest and not complete the long term rehabilitation process. In addition, these programs do not incorporate visual feedback targeting joint perception, which is an integral mechanism that helps compensate for impaired proprioception among DPN. Methods: This is a prospective randomized control trial study. Participants were randomized either in intervention or sham. The intervention group received twice per week an innovative exercise program based on virtual reality for 4 weeks. Their gait and balance were assessed at baseline prior initiating the intervention and after 4 weeks. Sham group were not included in balance training but their balance and gait were assessed at study visit and 4 weeks later. An innovative exercise program based on combination of wearable sensors technology and virtual reality was designed. The wearable sensors allow measuring lower extremity joint position in real-time which were used for the purpose of animation and real-time visual feedback to subject during exercise. Exercise program includes a series of ankle point-to-point reaching tasks in different direction as well as crossing a series of virtual obstacle with different heights, which were appeared on a computer screen in front of participants, Figure 1. Results: Forty-one eligible subjects have been recruited to date. However, the results of 15 participants (Age: 56.3±4.9, BMI: 30±15 m/Kg2) who completed the exercise program have been reported. Participants were diagnosed with diabetes by primary care and were confirmed to have peripheral neuropathy. The preliminary results suggest that active group reduced ankle sway by 76% (2.82±2.8deg to 0.66±0.47deg), hip sway by 81% (7.96±9deg to 1.48±1.2deg) and center of mass (CoM) sway by 76% (0.69±0.7deg to 0.16±0.11deg) during eyes open balance assessment. Similar reductions during eyes closed assessment were observed with reductions of 50%, 24% and 45% for ankle, hip and CoM sway. Conclusion: The current research implemented a novel balance rehabilitation strategy based on virtual-reality. Our methodology included wearable sensors and interactive user interface for real-time visual feedback based on ankle joint motion, similar to video gaming environment for compensating impaired joint proprioception. Findings support that visual feedback generated from ankle joint coupled with motor learning may be effective in improving postural control and gait among DPN patients.
Generic Results For The Effective+B168Ness Of Medical Male Circumcision As An Hiv Intervention In Sub-Saharan Africa
Authors: Abu-Raddad Laith
Published: November 2013

Background: The efficacy of medical male circumcision (MMC) in reducing female to male HIV transmission has been established by three clinical trials. Programs are being developed for massive roll-out of MMC as an HIV intervention across multiple countries in sub-Saharan Africa (SSA). We aimed in this study to explore generic results of the effectiveness of MMC as an HIV intervention. Method: A population-level deterministic model was constructed to describe a prototype heterosexual HIV epidemic in SSA. The model consists of a set of coupled nonlinear differential equations that stratifies the population into compartments according to sex, circumcision status, age group, sexual risk group, and HIV status and stage of infection. The model was parameterized by state of the art empirical data of HIV natural history and transmission. Sensitivity analyses with respect to different effects were conducted. Results: The effectiveness of MMC, defined as the number of MMCs needed to avert one HIV infection, was inversely proportional to HIV prevalence with as little as about 10 MMCs needed for each infection averted in settings at high HIV prevalence. The effectiveness also varied substantially with each of the 5-years age groups targeted, with the highest effectiveness found by targeting the 20-24 years age group. Risk targeting strongly affected the estimated effectiveness. MMC effectiveness was an order of magnitude higher by targeting the high-risk groups as opposed to the general population. The speed of scale-up influenced also the estimated effectiveness in the short-term, but was less influential for long-term time horizons. MMC was found to be generally cost-effective, with the cost per infection averted being less than $1000 for most settings. Conclusion: Our findings demonstrate that MMC is an effective HIV prevention intervention, and likely to be cost-effective in most settings in SSA. The highest MMC effectiveness is attained by targeting young sexually active males and high-risk groups. These generic results of MMC effectiveness suggest the need for custom-designed assessments for each country separately, taking into account the likely temporal evolution of the epidemic in the next few decades, the age and geographic distribution of HIV infection, population pyramid, and the country-specific cost for each MMC performed.
Advanced endometriosis: A diagnostic dilemma
Authors: Abreo Mohini Oswald
Published: November 2013

Endometriosis is a debilitating medical condition in females in which endometrial glands and stroma appear and flourish in areas outside the uterine cavity and walls, most commonly in the ovaries. Incidence in general population is 5-15% and around 30% in infertile women. Usual age group is 20-30years and patients present with dysmenorrhoea, dyspareunia, dyschezia, infertility and pelvic pain. We report two interesting cases of stage IV endometriosis who presented as bilateral complex ovarian masses which simulated ovarian cancer on ultrasound. MRI pelvis for both these cases diagnosed stage IV Endometriosis.
Italian study on gene-environment interactions in lymphoma etiology: Translational aspects
Authors: Gabbas Attilio
Published: November 2013

Introduction: The objective of the "Italian Study on gene-environment interactions in lymphoma etiology", hereafter named the Italian GxE Study, is to identify individual conditions and external factors associated with lymphoma aetiology, the response to therapy and survival, as possible targets for preventive action and possible drivers of new individualized therapeutic strategies. Methods: This objective is being pursued by recruiting up to 1000 incident lymphoma cases and 1000 controls in six Italian areas: central and southern Sardinia, Florence, Bari and Taranto, Verona, Novara and Perugia. After signing the informed consent form, cases and controls will donate a blood sample and respond to a detailed questionnaire on health history, lifestyle factors, and occupational and environmental exposures of interest. The interaction between genetic polymorphisms, epigenetic conditions, and the most prevalent lifestyle and occupational exposures will be explored using the case-control epidemiological study design. Survival analysis will be conducted in relation to the therapeutic protocol, lifestyle variables, and gene polymorphisms using a modified proportional hazard model. Study design: Here are the main features of the Italian GxE study: 1. Genome Wide Scan of patients and controls DNA, which aims to evaluate several million SNPs, some functionally known, and other in strict linkage disequilibrium with genes in loci encoding for known proteins, using last generation high throughput platforms (Illumina (R) Human660W). 2. Use of the Telepathology Network to reach maximum consensus among the pathologists' panel collaborating in this project so achieving the maximum diagnostic precision, by applying the most recent lymphoma classification schemes consistently across the study areas. 3. Detailed assessment of occupational and environmental exposure, thanks to the experts in retrospective exposure assessment participating in our project and the continuous refinement of the questionnaires which have been used in international studies for the last two decades. Precision in defining external exposures is of paramount importance to effectively explore gene-environment interactions in the aetiology of the different lymphoma subtypes. 4. Analysis of response to therapy and survival of lymphoma patients in relation to their genetic features, which will allow to design future individualized therapeutic schemes, by identifying responders to specific chemotherapeutic agents based upon their polymorphisms of genes implicated in xenobiotic metabolism, DNA repair, release of inflammatory cytokines, as well as other yet to be identified. Conclusion: The Italian GxE Study contributes to the International InterLymph Consortium (http://epi.grants.cancer.gov/InterLymph/), which creates the necessary synergy to inquire into lymphoma etiology in general, and its individual subtypes in particular.
Recovery of the genetic mutation of CFTR channel and the cystic fibrosis disease mechanism
Authors: Rabeh Wael
Published: November 2013

Cystic Fibrosis (CF) is a genetic disorder that is caused by mutations in the gene for the CF Transmembrane Conductance Regulator (CFTR). CFTR is an ABC transporter chloride channel containing five domains: two membrane-spanning domains (MSD1 & 2) connected by two nucleotide-binding domains (NBD1 & 2) and linked by a regulatory domain. The most common CF causing mutation is the deletion of phenylalanine 508 (?F508) in NBD1. It was shown that ?F508 thermodynamically destabilizes NBD1, as a result, misfold and degrade CFTR channel in the endoplasmic reticulum and prevents its processing and translocation to the plasma membrane. An effective drug that rescue the channel enhance its folding will increase its concentration on the plasma membrane. Here, we show stabilization of ?F508-NBD1 with second site mutations was not sufficient to increase the ?F508-CFTR folding efficiency and membrane concentration to that of the wild-type level. However, the introduction of additional mutations that stabilizes the interaction between NBD1 and MSD2 of CFTR in the presence of ?F508-NBD1 stabilization mutations increased the ?F508-CFTR folding efficiency and biogenesis from ~2% to 80% of the wild-type. As a result, a two-component drug that energetically stabilizes ?F508-NBD1 and maintain the NBD1-MSD2 interface interactions are required for wild-type like folding, processing, and transport function, suggesting a two step correction process.
QBB: Milestones in building a successful biobank
Authors: Afifi Nahla
Published: November 2013

Qatar Biobank (QBB), the first very large scale, long-term public biorepository in Qatar, is designed to build a powerful research infrastructure for future investigations of the lifestyle, metabolic and genetic risk factors by collecting comprehensive phenotypic baseline data among healthy volunteers, including ECG, blood pressure, anthropometry, spirometry, retinal imaging, carotid 3D ultrasound, arterial stiffness, total body iDXA, in addition to detailed personal lifestyle and clinical data. QBB collects and stores blood samples subdivided in 68 aliquotes for different future research purposes. Qatar Biobank understands that building a successful biobank depends on the willing participation of the public to come forward to contribute. The recruitment of participants requires insight into the public's existing knowledge of biobanking, level of willingness and an understanding of the motivators and barriers to participation. From December 2012 to June 2013, 503 participants completed anonymously a feedback form to evaluate their experience. The aim of this specific survey is to gain insight into recruitment methods, incentive to participate and satisfaction with various aspects of the visit. This will enable assessment of the processes of registration, scheduling, checking in, consent and reporting back results. Around 75% of those who completed the feedback form participated in QBB to improve the health of future generations and to have a comprehensive health checkup. 95% were willing to participate again if needed and 85% would recommend participation to friends and family. 87% and 95% thought the length of the questionnaire was appropriate and the questions not too intrusive, respectively. Finally, 91% found the staff welcoming, 89% rated the check-in process as "good" and 76% found scheduling an appointment straightforward. Further comments from participants suggested appreciation of the protection of confidentiality and privacy that was displayed throughout the process and that the process was smooth and enjoyable.
Global Status Of Drink-Driving-Related Fatality Reporting: Availability And Its Relationship With Use And Other Alcohol Mortality Patterns
Authors: Bhatti Junaid
Published: November 2013

Introduction: According to the World Health Organization one in five road traffic fatalities are related to impaired driving involving drunk-driving (DD), drugs, illicit substances as well as prescription medications. The proportion of DD-related road fatality (or DDRF %) is the recommended indicator in setting road safety goals for DD prevention. The literature however is relatively silent about the availability of DDRF % in high-income (HIC), medium-income (MIC) and low-income (LIC) countries. Objective: The study assessed the availability of DDRF % in different countries and particularly with respect to their income and alcohol use patterns. This research is in line with Qatar National Research Strategy pillar H.E.1.8 (prevention of motor vehicle crashes and injuries) and the Grand Challenges Qatar. Methods: Availability of DDRF % was extracted from the two recent global status reports on road safety (2009) and on alcohol and health (2011) and assessed with respect to country income and alcohol use patterns. Results: Report on road safety included more DDRF% than report on alcohol and health (n=90 vs. 27). DDRF% was significantly (P<0.01) more available in high-income countries (77%, n=30/39) versus middle income countries (52%, n=47/90) and low-income countries (28%, n=13/46). DDRF% distribution ranged from 5% to over 40%, however, we noted no differences between country's income status and the distribution of DDRF%. We did observe that DDRF%s were not available in the high-income countries of the Eastern Mediterranean Region. DDRF%s were available in 88% countries with high consumption (<20% abstainers) One in two countries with moderate consumption did not report DDRF%. Conclusions: Data on the contribution of DD to fatality rates are generally inadequate, especially in HICs of Eastern Mediterranean region, MICs and LICs. These findings indicate the need to strengthen road safety data collection on DD, drugs and medication use while driving in above mentioned countries.
Endothelial Adiponectin: Putative Role In Graft Patency In Patients Undergoing Coronary Artery Bypass Surgery?
Authors: Mohamed-Ali Vidya
Published: November 2013

Background: Blood vessels are comprised of three distinct layers, the intima, media and outermost layer, the adventitia that, in medium to large vessels, is surrounded by a cushion of perivascular adipose tissue (PVAT). PVAT is comprised of discrete adipocytes containing a network of capillaries and nerve fibres as well as a variety of other cell types. A number of adipokines have been identified in the PVAT of human blood vessels, including leptin and adiponectin. Since PVAT is in close proximity with the adventitia there is the potential for this layer to influence vessel tone and therefore blood flow. Of particular interest is the beneficial role PVAT may play in blood vessels used as bypass grafts in patients requiring coronary artery bypass grafting (CABG). This study investigated the expression of leptin and adiponectin in the main vessels used as bypass conduits, which include the internal thoracic artery (ITA) and saphenous vein (SV). Methods and Results: SV and ITA samples were obtained at heart surgery - all with PVAT intact. 'Local' subcutaneous fat (SV=calf/thigh; ITA = sternum) was also collected and used for: 1) ELISA, 2) histology and IHC vessels and, 3) mRNA expression. Human arterial and venous endothelial cell lines were established to ascertain endothelial leptin and adiponectin synthesis and regulation. Dense immunostaining for leptin was observed in the PVAT of both the vein and artery with no evidence of staining associated with endothelial cells lining the vessel lumen, the vasa vasorum or capillaries (as identified using CD31). Like leptin there was dense immunostaining for adiponectin in both the vein and the artery. However, discrete staining was also associated with endothelial cells lining the lumen of both the artery and the vein as well as to those of the vasa vasorum and capillaries embedded in PVAT. No leptin mRNA expression was detectable in either arterial or venous endothelial cell lines, however, adiponectin was present in both and appeared inducible by insulin. Conclusions: We show, for the first time, that the endothelium expresses adiponectin and that endothelial cell adiponectin appears to increase upon insulin stimulation. Whether these adiponectin concentrations are of functional importance in the endothelium and contribute to the vasodilatory capacity of grafted vessels are yet to be ascertained.
Noradrenaline-Induced Arteriolar Contractile Insensitivity And Collagen Deposition In Adipose Tissue Of Diabetic Patients
Authors: Mohamed-Ali Vidya
Published: November 2013

Background. Norepinephrine (NE) is a powerful regulator of various adipose metabolic and vascular functions, including vasoconstriction and tissue fibrosis. Recent data suggests that this may be through autocrine/paracrine effects on local resistance vessel function and morphology. Therefore, the aims of this study were to investigate in human sub-cutaneous and omental adipose tissue (SAT and OAT): 1) NE synthesis, 2) NE-mediated arteriolar vasoconstriction from non-diabetic versus diabetic obese subjects, 3) the induction of collagen genes and its deposition in the tissue. Methods and Results. AT from the abdominal subcutaneous and intra-abdominal greater omental depots was obtained during surgery (~5g each) and quickly transported in serum-free medium to the laboratory. The tissue was used for (i) histology and immunohistochemical analysis, (ii) dual wire myography for assessment of vascular reactivity, (iii) organ culture for assessment of NE release, (iv) protein extraction and NE ELISA, and (v) collagen gene type IÎ±1 mRNA expression. In the non-diabetic group: TH immunoreactivity, NE concentration, and maximal vasoconstriction were significantly higher in OAT compared to SAT (p<0.05). But arterioles from OAT showed lower NE sensitivity compared to SAT (Log EC50: SAT versus OAT, -7.3±0.6 versus -6.2±0.6, p<0.01). In the diabetic group: no significant depot differences were seen in NE synthesis or vasoconstriction. SAT arterioles showed significantly lower sensitivity to NE (10-8 M to 10-7.5 M, p<0.05) compared to non-diabetic group. Collagen deposition and gene expression were greater in OAT than SAT of non-diabetics, while levels were elevated but comparable within both depots of diabetic subjects. Conclusions. Elevated, chronic, local NE synthesis in OAT of non-diabetic subjects may desensitize NE-induced vasoconstriction, as greater NE synthesis in both depots of diabetic patients may explain the abolishment of the depot-specific differences and sensitivity to NE in obese patients. High NE levels may also explain greater collagen gene expression and its deposition in the OAT and in diabetes.
Orai1 trafficking in mammalian cells
Authors: Hodeify Rawad
Published: November 2013

Modulation of calcium homeostasis plays a key role in regulating fundamental cellular processes, including gene transcription, cell proliferation, differentiation, and apoptosis. Store-operated calcium entry (SOCE) is the major pathway in non-excitable cells for extracellular Ca2+ influx across the plasma membrane and is regulated by the content of the intracellular Ca2+ stores. Following store depletion, the Ca2+ sensor in ER, stromal interaction molecule 1 (STIM1) clusters in ER regions close to the plasma membrane and recruits Orai1, which is a Ca2+ selective channel resulting in SOCE. Despite the significant knowledge in understanding STIM1 subcellular distribution dynamics, little is known about the trafficking of Orai1. Our laboratory previously showed that in Xenopus leavis oocytes Orai1 shuttles between plasma membrane and endosomal compartments, and that it internalizes during meiosis. However, the subcellular distribution and trafficking of Orai1 in mammalian cells is not fully understood. In this study we show that at steady state around 46% of Orai1 is on the surface of the plasma membrane of CHO cells, while the remaining 54% localizes intracellularly, suggesting that Orai1 constitutively recycles between the two compartments. Our time lapse imaging shows continuous shuttling of Orai1 to and from the PM with an exocytosis rate T1/2 of around 5 minutes. We also measured the endocytic rate of Orai1 at 5% min-1. To identify the domain within Orai1 required for its trafficking, we generated deletions of either the N- or C-terminus of Orai1. Deletion of N-terminus does not affect Orai1 trafficking to the cell membrane in CHO cells. In contrast deletion of the whole C-terminus (257-301) significantly altered Orai1 trafficking to the cell membrane. Deletion of amino acids 285-301 of Orai1 C-terminus does not have any impact on Orai1 trafficking to PM, suggesting that the information necessary for Orai1 trafficking to PM is located in the segment 257-285 of Orai1 C-terminus. In this study we determined, for the first time, the percentage of Orai1 on PM of mammalian cells and showed through time lapse-imaging that it constitutively recycles between PM and intracellular compartments. Our results also suggest, for the first time, that the amino acid region (257-285) of Orai1 C-terminus is essential for its plasma membrane trafficking.
Chronic elevation of systemic glucagon-like peptide-1 following surgical weight loss: Association with nausea and vomiting and effects on adipokines
Authors: Mohamed-Ali Vidya
Published: November 2013

Gastric bypass surgery is the most effective treatment for obesity, achieving both sustained weight loss and improved insulin sensitivity. However, following Roux-en-Y gastric bypass surgery (RYGB) some patients develop debilitating nausea and vomiting (N/V) persisting for years. The aim of this study was to determine if the N/V following RYGB is due to elevated systemic GLP-1 levels and whether GLP-1 directly mediates secretion of adipokines, such as leptin. 42 female non-diabetic subjects were studied in the fasting and post-prandial state and divided into 5 groups according to BMI and presence of N/V post-operatively. The effect of GLP-1 on adipose tissue leptin secretion in vitro was measured. Subjects with N/V post-RYGB surgery had significantly elevated fasting GLP-1 levels compared to post-operative subjects without N/V symptoms, and to morbidly obese (MO), obese and lean subjects not undergoing surgery. However, weight loss, as well as systemic levels of glucose, insulin and post-prandial GLP-1 was similar in all post-operative subjects. Despite similar BMI (P = 0.86) and fasting adiponectin levels, leptin was significantly lower in subjects with N/V compared to those without N/V (P = 0.04). Leptin secretion from subcutaneous adipose tissue in vitro was significantly inhibited by GLP-1 (0.1-1.0 nM; n = 6). Persistent N/V following RYGB surgery is associated with elevated fasting GLP-1 and lower leptin levels, perhaps as a consequence of GLP-1 mediated inhibition of leptin secretion from adipose tissue. GLP-1 antagonists may alleviate these symptoms, but, adverse effects on weight maintenance and insulin sensitivity need to be considered.
Estrogen receptor α gene and vitamin K epoxide reductase (VKORC1) gene haplotypes and low BMD in Palestinian postmenopausal women
Authors: Darwish Hisham
Published: November 2013

Background Osteoporosis is a common skeletal disorder characterized by low bone mass and microarchetectual deterioration of bone tissue with increased susceptibility to fractures. Osteoporosis is considered a multifactorial polygenic disease. The prevalence of postmenopausal osteoporosis in Palestine, based on of BMD at femoral neck, total hip and spine was 24%, 14% and 29.7% respectively. Previous studies on the effect of genetic polymorphisms on bone mineral density (BMD) showed significant correlation between various haplotypes and mutations in the VDR and MTHFR and low bone mineral density [BMD] among Palestinian postmenopausal subjects. Estrogens are known to play an important role in regulating bone homeostasis. Estrogen act through binding to Estrogen Receptor α (ERα) which is a member of the nuclear receptor superfamily of ligand activated transcription factors. Vitamin K hydrochinon is an important cofactor for gamma carboxylation of osteocalcin, a major bone matrix protein . The reduction of vitamin K to vitamin K hydrochinon depends on the vitamin K epoxide reductase complex subunit 1 (VKORC1). Aim In the present study, correlation between specific XbaI and PvuII polymorphisms in the ERα gene and selected polymorphisms in the VKORC1 gene with low BMD and fractures risk were investigated in 345 postmenopausal Palestinian women including 165 osteoporotic, 93 osteopenic and 86 normal subjects using allele-specific polymerase chain reaction (PCR) and RFLP-PCR technology. Results The data showed significance association between the XX haplotype of the XbaI in ERα gene and lower BMD at the hip (P=0.012). Similarly the PP haplotype of PvuII ER α gene was significantly associated with lower hip BMD ( P=0.03). In addition, the 9041G allele [GG and GA] was significantly more frequent in patients with low BMD (P = 0.012). In our cohort, a genetic variation in the 3'-region of the VKORC1 gene (9041 AG and GG) was significantly associated with low BMD. The data also revealed the +2255 TT haplotype which is linked to lower activity of the enzyme was associated with low BMD while the presence of the C allele [CC or CT], linked to higher activity at this locus, was associated with normal BMD levels [P=0.02]. Conclusions These findings indicate that specific polymorphisms in the ERα gene and VKORC1 gene are correlated with variation in BMD levels among our subjects. These results along with previous data with the VDR and MTHFR genes provide evidence for the strong correlation between genetics and osteoporosis in our population may be significant for treatment decisions and screening of osteoporotic patients. The involvement of other genes variation like the osteoprotegrin and TNF superfamily member genes are underway. The overall data will eventialy be employed for direct correlation and evaluation between the genetic background of patients and the efficacy of selected specific drugs used to treat osteoporosis.
Role of cell adhesion molecules in invasion, anoikis resistance and drug resistance: An in vitro analysis using multiple phenotyping approach
Authors: Abdul Azis Thasni
Published: November 2013

Epithelial ovarian carcinoma (EOC) is an aggressive neoplasm that mainly metastasizes to organs of the peritoneal cavity. This event is mediated by molecular mechanisms that remain elusive. Cell adhesion molecules play a key role in tumor invasion, metastasis and drug resistance. The conventional in vitro two-dimensional cell culture models are not sufficient to explain the exact mechanism behind tumor invasion, migration and anoikis resistance events. The objective of the present study is to analyze the role of cell adhesion molecules in tumor invasion metastasis and drug resistance using multiple phenotyping approach. Five ovarian cancer cell lines PA1, SW626, CAOV3, SKOV3 and OVCAR3 were selected for the study. Cell line phenotyping was conducted using cultured cells in an anchorage independent method that utilized an ultra low attachment plate for mimicking anoikis resistance in vitro. Second type phenotyping was done for sorting highly invasive phenotype by selecting cells that can pass through Boyden chamber (8 micron pore size upper chamber membrane). Development of drug-resistant cell lines were achieved by growing cells in culture media containing standard chemotherapeutic agents such as Taxol and Carboplatin. Cells were selected according to their ability to attach different ECM and cell adhesion molecule coated chambers. A real time PCR array of 29 genes involved in cell adhesion, drug resistance and EMT (epithelial-mesenchymal transition) were also analyzed and gene expression analysis conducted. The invasive potential of PA1 (teratocarcinoma) seems to be higher than other cell lines followed by SKOV3 cells. PA1 cells form embryoid bodies while culturing in in anchorage independent condition and exhibit an elevated level of expression of myc and TGF beta. Cell viability assay also shows that PA1 is the most sensitive cell line against carboplatin and taxol. Gene expression levels of cell adhesion molecules were altered among the phenotypes. Anoikis resistant cells show altered levels of expression in EPCAM, Collagen 6, CD24, vimentin and N-cadherin. These results suggest the cell lines are heterogeneous in nature and three dimensional culture model mimics the in vivo tumor model for anoikis resistance and EMT. To conclude, this study shows selection of various phenotypes of heterogeneous cancer cell lines can help decipher the role of cell adhesion molecules in ovarian cancer invasion and drug resistance. These experiments will give an overall view of the role of cell adhesion molecules in different ovarian cancer types in vitro.
Reliability Of Bess Test For Concussion In Different Field Conditions
Authors: Azad Aftab
Published: November 2013

Introduction: Mild Brain Injury or concussion is frequently observed during contact sports such as football and soccer. If it remains undetected, a repeat concussion can lead to long term consequences because of the vulnerable brain tissue damage. Balance Error Scoring System (BESS) test is a widely used test to detect concussion. It requires the athlete with suspected concussion to maintain his/her position in three different stances, that are, both legs, single leg and tandem, and has a total score ranging from 0 to 30. The recommended way of performing this test is to do it barefoot in clinical or semi-clinical settings. Such conditions are however difficult to achieve during an ongoing match, and athletes would like to be near the field with their cleats on - situations often found on soccer fields in eastern countries. Objective: Therefore, we aimed to assess the reliability of BESS test in different field conditions. This research is in line with Qatar National Research Strategy 2012 pillars, H.E.1.9 (prevention of brain Injury) and H.E 1.10 (control of sports injuries). Methods: This study was conducted under the auspices of McGill Sports Emergency Medicine Clinic. Athletes from soccer and football teams were approached on the field during practice games. After informed consents, they performed BESS test in three conditions, that were, barefoot, on turf with cleats and on hard surface with cleats. Each athlete was rated by three observers independently of each other. We computed mean difference in total BESS scores with 95% confidence intervals (95%CI). Comparison of total BESS scores under different conditions as well as inter-observer reliability was assessed using intraclass correlation coefficient (ICC).. Results: We recruited 49 athletes from football (n=39) and soccer (n=10) teams in this study. Thirty nine of them were male, 10 were females. Average age was 21.1 years (standard deviation [SD]=1.9). We found that total BESS scores were significantly different (P<0.001) between barefoot and the two conditions with cleats-on: 2.2 (95%CI=1.6, 2.8) for turf and 2.0 (95%CI=1.4, 2.6) for hard surface. Concordances of barefoot with turf (ICC=0.47, P=0.02) and hard surface (ICC=0.51, P=0.01) conditions were moderate. A moderate to high inter-observer reliability (0.60â‰¥ICCâ‰¤0.75) was observed for BESS test under three conditions. Conclusion: These findings show that BESS test has a fair reliability under different conditions, and may be useful in screening concussion on the field. However, cut-off of BESS should be reduced by 1 to 2 points if it is applied on the field with cleats.
Insulin resistance alters noradrenergic sensitivity of omental vessels from morbidly obese Qataris
Authors: Bakhamis Aysha
Published: November 2013

Background: Expanding adipose tissue in obesity requires effective angiogenesis and vasoreactivity to combat hypoxia and its consequences, such as insulin resistance and type-2 diabetes. While recent evidence suggests that the adipose tissue is highly angiogenic and inflammed, the tissue arteriolar vasoreactivity has been less investigated. As a consequence of the inflammation the omental adipose tissue (OAT) also synthesizes greater levels of vasoconstrictive molecules, such as cytokines and catecholamines, compared to the sub-cutaneous (SAT) depot, and these are likely to impact on the maintenance of vascular tone leading to greater susceptibility to hypoxia. This study compared the contractile responses of OAT and SAT arterioles from insulin-resistant (IR) and insulin-sensitive (IS) morbidly obese non-diabetic Qatari patients. Methods: Segments of arterioles (ID ~240-250 µm) isolated from SAT and OAT obtained from obese non-diabetic Qatari patients (age ~29 years, BMI ~40kg.m-2), undergoing bariatric weight reduction surgery, were mounted on a dual wire myograph (510A) and investigated for noradrenergic responsiveness. Cumulative concentration-response curves were constructed for noradrenaline (10-9 -10-5 M). Curves were also constructed for potassium chloride (KCl, 1-70 mM). Results: OM arterioles from IR patients were significantly less sensitive to NA compared with SAT arterioles from same patients (log EC50 -5.9±0.2 vs. -6.5±0.1, p<0.05). Maximum NA contractile response was also attenuated in OAT compared with SAT vessels (p<0.05) from these patients. On the other hand, KCl curves were comparable for OAT and SAT vessels from the same patients. In addition, no differences in noradrenergic sensitivity were observed between OAT and SAT vessels from IS patients. Conclusions: The data suggest that insulin resistance selectively alters noradrenergic responsiveness of OAT arterioles compared with SAT vessels from morbidly obese non-diabetic Qataris. Differences in adrenoceptor density/function may underlie these depot-specific responses. Studies on the disease specific differences need further investigation.
A Novel De Novo Pstpip1 Mutation In A Boy With Pyogenic Arthritis, Pyoderma Gangrenosum, Acne (Papa) Syndrome
Authors: El-Shanti Hatem
Published: November 2013

Autoinflammatory disorders are a group of Mendelian disorders characterized by seemingly unprovoked inflammatory bouts without high-titer autoantibodies or antigen-specific T-cells and are probably due to defects in the innate immunity. We here report on a 4-year old Arabic child with the clinical presentation of an autoinflammatory disorder, namely Pyogenic Arthritis, Pyoderma Gangrenosum and Acne (PAPA) syndrome. The presentation includes abscess formation after immunization and recurrent mono-articular acute arthritis in various joints that responded favorably to systemic glucocorticosteroids, albeit without acne or pyoderma gangrenosum. The mutation analysis of the child identified a novel de novo mutation in PSTPIP1, the gene responsible for PAPA syndrome. We recommend that the diagnosis of PAPA syndrome should be entertained in the differential diagnosis of patients with recurrent sterile pyogenic arthritis prior to the development of pyoderma gangrenosum or acne in order to initiate a timely management of the disorder.
Thymoquinone regulates expression of IL-8 and TRAIL receptors, induces apoptosis and suppresses growth of human hepatocellular carcinoma via oxidative stress
Authors: Ashour Abdelkader
Published: November 2013

Hepatocellular carcinoma (HCC) is the fourth most common solid tumor worldwide. The chemokine interleukin-8 (IL-8) is overexpressed in HCC and is a potential target for therapy. Although the transcription factor nuclear factor kappa B (NF-?B) regulates IL-8 expression, and while thymoquinone (TQ), the main active constituent of black seed essential oil, inhibits NF-kB activity, the precise mechanisms by which TQ regulates IL-8 expression and cancer cell growth remain to be clarified. Here, we report that TQ inhibited growth of HCC cells in a dose- and time-dependent manner, caused G2M cell cycle arrest, and stimulated apoptosis. Apoptosis was substantiated by activation of caspase-3 and -9, as well as cleavage of poly(ADP-ribose)polymerase (PARP). TQ treatments inhibited expression of NF-?B and suppressed expression of IL-8 and its receptors. TQ treatments caused increased levels of reactive oxygen species (ROS), and mRNAs of oxidative stress-related genes, NAD(P)H:quinoneoxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1). Pretreatment of HepG2 cells with N-acetylcysteine, a scavenger of ROS, prevented TQ-induced cell death. TQ treatment stimulated mRNA expression of pro-apoptotic Bcl-xS and TNF-related apoptosis-inducing ligand (TRAIL) death receptors, and inhibited expression of the anti-apoptotic gene Bcl-2. TQ enhanced TRAIL-induced death of HepG2 cells, in part by up-regulating TRAIL death receptors, inhibiting NF-kB and IL-8, and stimulating apoptosis. Altogether, these findings provide insights into the pleiotropic molecular mechanisms of TQ-dependent suppression of HCC cell growth, and underscore potential of this compound as anti-HCC drug.
Unraveling molecular switches determining cell fate
Authors: kolatkar prasanna
Published: November 2013

The Yamanaka factors (Oct4, sox2, Klf4, cMyc) used to produce induced pluripotent stem cells (iPSC) have become a staple of stem cell biology and ChIP-seq studies have led to an understanding of the genomic landscape of how these as well as other recently discovered factors transduce their effects to form iPSC. A conundrum that previously existed was that the Sox family has high homology and yet various members drive completely different cell fates. My lab in collaboration with Larry Stanton's lab at the Genome Institute of Singapore unraveled part of the mystery by identifying and validating a single residue within the hmg domain of the Sox family responsible for a specific interaction with Oct4 (pou5F1 domain) which then decides specific cell fates. In addition a novel genomic motif was discovered which has a single base difference between the Oct4 and Sox binding sites. Using this knowledge we were able to transform the function of pluripotent Sox2 into an endodermal TF and endodermal Sox17 into a pluripotent TF. In fact the mutated Sox17 TF was even more efficient in forming iPSC (compared to Sox2) which was not expected. Recently we investigated the C-terminal activation domains of these Sox family members and discovered that they play a major role in the level of activation of iPSC. Conversion of Sox17 into a Pluripotency Reprogramming Factor by re-engineering its Association with Oct4 on DNA. Ralf Jauch, Irene Aksoy, Andrew Paul Hutchins, Calista Keow Leng Ng, Xian Feng Tian, Jiaxuan Chen, Paaventhan Palasingam, Paul Robson, Lawrence W. Stanton and Prasanna R Kolatkar. Stem Cells. 2011. Jun;29(6):940-51. Oct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm. Aksoy I, Jauch R, Chen J, Dyla M, Divakar U, Bogu GK, Teo R, Leng Ng CK, Herath W, Lili S, Hutchins AP, Robson P, Kolatkar PR, Stanton LW. EMBO J. 2013. 32(7): 938-53. Sox transcription factors require selective interactions with Oct4 and specific transactivation functions to mediate reprogramming. Aksoy, I., Jauch, R., Eras, V., Bin, A.C-W., Chen, J., Divakar, U., Ng, C. K-L., Kolatkar, P.R., Stanton, L.W. Stem Cells. 2013.
Evaluation of natural polymers with permselective properties aiming at the development of biosensors for the detection of mycotoxins in food
Authors: Migheli Quirico
Published: November 2013

A biosensor combines the specificity of a biological component with the sensitivity of an electrochemical transductor. The variable inhibition showed by aflatoxin and other mycotoxins towards acetyl choline esterase (AChE) can be exploited in a multi-enzyme biosensor design: the more AChE is inhibited by mycotoxins, the less choline is oxidized by choline oxidase (ChO) to betaine aldehyde and H2O2. Hence, the H2O2 oxidation signal is influenced by the presence of mycotoxin. In the present study, AChE and ChO were co-immobilized onto a Pt/Ir electrode surface coated with different electrosynthesized polymers. In order to prevent signal of interferents, ortho-phenylendiamine (oPD) is currently utilized. Quite regrettably, this compound is highly carginogenic and alternative, non toxic, polymerizing compounds would be highly desirable. We have tested different permselective films generated by non-toxic natural monomers belonging to phenylpropanoids and C2-symmetric dimers. The compounds were electropolymerized by constant potential amperometry (CPA) and by cyclic voltammetry (CV) and characterized by scanning electron microscopy (SEM) and permselectivity analysis. Differences in permselectivity towards H2O2 over ascorbic acid and dopamine were detected in poly-monomers and poly-C2-dimers. The presence of a 2-propenyl chain in the phenol ring seems to enhance permeselectivity and electrocoating quality. A bi-enzyme sensor with AChE/ChO coated with these natural compounds may therefore represent a promising analytical device for mycotoxin detection in agricultural and food matrices. *The first two authors have equally contributed to the present work.
Impact Of Metabolic Health On Microvascular Endothelial Function In Morbidly Obese Qataris
Authors: Orie Nelson
Published: November 2013

Background & objectives: Vascular complications account for much of the morbidity of obesity. The proportion of Qatari population that is overweight or obese is one of the highest in the world. With this comes the increased risk of blood vessel dysfunction and predisposition to type 2 diabetes and hypertension. The vascular endothelium is often the first target of the negative impact of obesity. It is however unclear how the heterogeneity in the metabolic status of obese individuals (ie metabolically healthy [MHO] vs. Pathologically obese [PO]) will impact on endothelial function, particularly in a relatively young obese population, as in Qatar. This study investigated endothelium-dependent relaxation of small arteries embedded in the visceral (omental) and subcutaneous adipose tissues in morbid obesity with varying metabolic status. Methods: Arteries were isolated from abdominal omental (OM) and subcutaneous (SC) fat collected from consented Qatari patients undergoing bariatric surgery for weight reduction. The arteries (normalized luminal diameter ~250 µm for SC and ~ 240 µm for OM) were cut into segments (~2 mm) and mounted on a dual wire Myograph (510A) for measurement of isometric tension. Cumulative concentration-response curves were constructed for acetylcholine (1- 30000 nM, the classical endothelium-dependent relaxant) in the absence or presence of NÏ‰-Nitro-L-arginine methyl ester (L-NAME,100 µM, nitric oxide [NO] synthase inhibitor) on initial tone generated with noradrenaline (5 µM). Relaxation to sodium nitroprusside (SNP, an NO donor) was also recorded. Results: There were no differences in age (~32 years), blood glucose (~5.6 mmol/L) and body mass index (BMI , ~ 43.4 Kg.m-2) between the MHO and PO patients . Insulin levels were 3 vs 19 µU/ml for MHO vs PO patients and their indices of insulin resistance (HOMA) were 1 vs 5 respectively. In general, relaxation to Ach was significantly attenuated in OM vessels (Emax 44±8 %) compared with SC vessels (Emax 78±4 %, p<0.01) from same patients. In contrast, relaxation to SNP was greater in the OM compared with the SC vessels. When Ach relaxation of the OM vessels were separated according to the patients' metabolic status, the MHO patients had significantly improved result compared with PO patients. On the other hand, relaxation of SC vessels from both groups of patients were comparable. In both vessel types, L-NAME caused a right-ward shift in the Ach curves. Conclusions: These results suggest that the metabolic status of obese Qatari patients has bearing on the physiology of their microvascular endothelium. The data also demonstrate that early changes in endothelial vasomotor function are depot-specific, being more marked in OM compared with SC vessels of pathologically obese patients.
Use of supplements and alternative medicine practitioners: Perceptions of college students in Qatar
Authors: Mamtani Ravinder
Published: November 2013

Abstract The use of herbal and nutrition supplements is widespread. It has been reported that about 80% of the world's population use herbal medicines [1, 2, 3, 4]. Very few supplement use studies have been conducted in the Gulf Cooperation Council (GCC) and neighboring nations (5,6). Supplement use data among young adults is scarce. In one study aimed at determining the use of supplements among athletes in Qatar (5), over 60% of the study participants reported using vitamin supplements. Data regarding attitudes on the use of supplements among young adults is almost non-existent. The data on their perceptions about alternative medicine practitioners is also inadequate. We thus conducted a survey in which we examined the a) prevalence of supplement use among college students in Qatar, and b) their perceptions about the use of supplements and alternative medicine practitioners. We have previously presented our study findings regarding the use of supplements (7). At this meeting we will present our study findings concerning the perceptions of college students about the a) effectiveness and safety of supplements and b) alternative medicine practitioners. References 1. Eisenberg, DM, Davis, RB, Ettner, SL et al. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA 280: 1569-1575, 1998. 2. Farnsworth, NR, Akerele, O, Bingel, AS., Socjata, DD, Eno, Z. Medicinal plants in therapy. Bull World Health Organization 1985: 63: 965-981. 3. Gesler, WM. Therapeutic landscape medical issues in light of the new cultural geography. Soc.Sci. Med. 1992; 34: 735-746. 4. Rafferty, AP, McGee, HB, Miller, CE, Reyes, M. Prevalence of complementary and alternative medicine use: state-specific estimates from the 2001 Behavioural Risk Factor Surveillance System. Am. J. Public Health 92: 1598-1600, 2002. 5. Knez WL and Peake JM, The prevalence of vitamin supplementation in ultraendurance triathletes. Int J Sport Nutr Exerc Metab. 2010 Dec;20(6):507-14. 6. Abu-Irmaileh, BE, Affi, F.U. Herbal medicine in Jordan with special emphasis on commonly used herbs. J. Ethnopharmacology 89: 193-197, 2003. 7. Mamtani R, MacRae B, Mahfoud Z, Cheema S , El Hajj M, Lopez T and Lowenfels A. Use of herbal and nutrition supplements among college students in Qatar. American Society of Clinical Nutrition, 2013, Dubai. Acknowledgement: This work is supported by the Biomedical Research Program at Weill Cornell Medical College in Qatar, a program funded by Qatar Foundation.