Qatar Foundation Annual Research Forum Volume 2011 Issue 1

Background: Body core temperature fluctuates during the day following a sinusoidal variation with a maximum acrophase in the late afternoon. This circadian rhythm is mainly endogenous but it can be influenced by environmental factors such as work and social and physical activities.

Objectives: 1) To verify if aluminum shift-workers would present different core temperatures at different times of the day (i.e. diurnal variations); 2) To characterize these diurnal variations and their consequences.

Methods: Twenty-nine employees from the aluminum industry participated in this preliminary study. They worked indoors where the temperature was typically in excess of 40°C. In addition, each worker wore protective clothing consisting of suit, gloves and mask. Core temperature (ingestible pill) data covering a 24-hour circadian cycle were obtained in 10 workers during morning, afternoon and night shifts. Circadian variation in temperature was characterized using a cosinus function (cosinor model). The mesor (average) and acrophase of the function have been calculated for each participant.

Results: Core temperatures recorded on the work site were significantly higher in the afternoon or early evening (from 12:00h to 20:00h) than at night or during the early morning (from 21:00h to 08:00h). These differences were not triggered by the work duration but by the time of day. There were large differences between the individual accrophase times, probably due to different working activities as well as the influence of synchronization/shift from the previous days. However, core temperature was consistently higher in the afternoon than during the morning or night. The circadian variation in body core temperature showed a mesor of 37.45°C. This represents an average core temperature half a degree higher than generally observed in the general population at rest.

Conclusions: The current data showed that workers from the aluminum industry present a relatively elevated average core temperature, with the highest values being reached during the afternoon shift. This suggests that special attention should be given to the afternoon shift and that break/cooling procedures should be implemented if necessary. These preliminary observations have to be completed by clinical and behavioral observations.

Background: Schoolchildren must practice healthy diet as well as active lifestyle to support their physical growth and development. Previous studies have shown that intermittent fasting can affect dietary intake, sleep duration and circadian patterns among adults, but there is a lack of related literature in schoolchildren.

Purpose: The aim of this study was to objectively assess the effect of Ramadan fasting on physiological parameters in young children.

Methods: Eighteen boys aged 12.6±1.5 years were assessed at baseline (BR) and followed up twice during Ramadan (1st week [R1], 4th week [R4]) and once two weeks after the end of Ramadan (AR). Body composition was assessed using anthropometry and DXA scan. Blood investigations included complete blood count, lipid profile analysis and iron indices. Pattern of daily activity and core body temperature were recorded using a triaxial accelerometer and ingestible thermistor pill, respectively. Dietary intake was assessed by experienced nutritionist based on digital images of food and drinks consumed by each participant during a 24-hour period. Repeated sprints tests (RSA) of 6 × 15 m sprints interspaced by 15 s rest were performed to evaluate fatigue resistance.

Results: There was a shift in daily peak activity from daytime (5:30 PM) to late night (12:00 AM) that resulted in 1.8±0.6 hours of loss in total sleep time during R4 (P<0.01). After 30 days of fasting there were no important change in lipids, but a significant drop in serum iron from 17.7±1.6 μmol/L at BR to 13.1±1.4 μmol/L (P<0.01), suggesting a potential nutritional deficiency. Moreover, reduction in serum iron was associated with younger age (r=0.47, P=0.05) and lighter body weight (r=0.37, P=0.13). Dietary analysis showed that subjects consumed a high calorific diet deficient in fruits and vegetables during Ramadan that explains weight gain (+1.0±0.2 kg, P=0.001) and consequently longer sprint times on RSA test (+0.4±0.1 s, P=0.04) at R4 compared to baseline.

Conclusion: This study concludes that intermittent Ramadan fasting may have an undesirable impact on body composition, sleep patterns and nutritional habits in young schoolchildren. These results could be used to develop educational strategies to promote a healthy lifestyle in schoolchildren during Ramadan.

Background: Exercise-induced hyperthermia is associated with a decrease in force production capacity during brief (<5 seconds) and sustained (>10 seconds) maximal voluntary isometric contractions (MVIC). A reduction in central nervous system drive to exercising muscles is suggested to mediate this decrement to prevent thermal injury. Until recently, the influence of exercise modality on neuromuscular function in the heat remained unclear. Two studies have since elucidated the role of constant load and self-paced exercise on force production capacity and voluntary activation during hyperthermia.

Methods: Study one evaluated neuromuscular function after a 40 km cycling time trial in hot (35°C) and cool conditions (20°C). In study two, muscle function was evaluated after passive heating via water immersion to a core temperature of 39.5°C and following constant load exercise to exhaustion at 60% of maximal oxygen uptake (38°C conditions). Prior to (control) and following each intervention, a sustained MVIC (20 s and 45 s, respectively for study 1 and 2) was performed to measure force production. Voluntary activation of the knee extensors was measured via percutaneous electrical stimulation at three intervals during each MVIC.

Results: Following self-paced exercise, mean force production decreased similarly in hot (15%) and cool (14%) conditions compared with control, despite a difference in core temperature of 0.8°C (P<0.001). A reduction in mean voluntary activation (P<0.05) accounted for ∼20% of the decrement in force. Interestingly, the extent of decline in voluntary activation was sustained for the duration of MVIC and did not progressively decrease. In the second study, mean force production was reduced following both interventions, but the magnitude of decline was more pronounced after exercise (P<0.05). As with study one, the decline in voluntary activation was similarly maintained (∼93%) following both interventions, with central fatigue accounting for <45% of the loss in force.

Conclusion: The loss of force production following exercise-induced hyperthermia appears to stem for both central and peripheral fatigue factors. Modality does not appear to influence neuromuscular function when exercise duration is similar and final core temperature is within ∼1°C. The combination of exercise and heat stress exacerbates the loss of force due to prior contractile activity.

Sleep spindles, along with K-complexes are hallmarks of stage 2 non rapid eye movement (NREM) sleep EEG. Sleep spindles are of significant interest because they are associated with phenomena such as ‘stability’ of sleep, updating of knowledge with new memories, processing of sensorimotor and mnemonic information. Therefore, accurately marking their presence in sleep recordings is essential.

Accurate identification of spindles in EEG recordings has proved to be a time consuming task, even with the help of experts. Further, manual detection by different experts introduces disparity and biases due to inter-rater differences. Hence there is a crucial need for an automated detection algorithm.

The objective of this paper was to develop a robust algorithm for real-time automated spindle detection based on the wavelet packet decomposition. The developed algorithm replicates the marking methodology used by sleep specialists to identify spindles. Spindles are transient 11–16 Hz oscillations present in NREM with higher amplitude than the background delta waves. To identify the spindles the EEG data was divided into epochs from which appropriate features were extracted to differentiate spindles from the background EEG. The feature vectors used included the level of EOG activity, the quantity of significant peak-to-peak transitions, the wavelet packet energy (WPE) within the frequency band of interest (11–16 Hz) and the presence of K-complexes. EOG activity was tracked to identify NREM sleep sections. Spindles were marked as being present in those epochs in which the WPE and peak-to-peak activity were higher than predetermined thresholds. The thresholds were reduced on detection of K-complexes, mimicking manual scoring.

The accuracy of the developed algorithm was verified by comparing to the manual scoring performed by a sleep specialist on the EEG data. The results from the algorithm look promising with a good degree of agreement with the manual scoring. When run on 3 hours of EEG data with 52 manually scored spindles the algorithm successfully detected 42 of them (80.7%) and of the total 21,600 epochs analyzed 290 were falsely detected as containing spindles. It was also observed that the true detection rate increases on varying the thresholds although this introduces further false detections.

Intorduction: Posaconazole (PZ), an antifungal prophylactic therapy in hematologic cancer patients, was added to Al-Amal Hospital formulary in 2010. The objectives of this study are: 1. To identify the practice guidelines and pharmacokinetics information regarding PZ use in Qatar and worldwide. 2. To conduct a drug use evaluation (DUE) report at Al-Amal Hospital.

Methods: Literature review was conducted to answer the first objective. A retrospective DUE report was conducted to include 10 randomly chosen hematologic cancer patients who used PZ during the year 2010. Patients profiles were reviewed and data were collected into a pre-prepared collection sheet.

Results: PZ was approved for prophylaxis in hematologic cancer patients →13 years in USA, Canada, and Australia, →18 years in the European Union and >15 years in Qatar. PZ has low bioavailability that can be enhanced by co-administration of high fat meals and by dividing the total daily dose. Data regarding PZ TDM is controversial. PZ undergoes several drug-drug interactions. For example, co-administration of proton pump inhibitors may result in PZ sub-therapeutic levels. Co-administration of vincristine may result in higher neurological toxicity, mainly gastrointestinal problems, due to the inhibitory potency of PZ on cytochrome P450 enzymes. A patient receiving vincristine based chemotherapy protocol concurrently with PZ developed seizure. Another patient developed mild breakthrough fungal infection while on PZ prophylactically.

Conclusion: The PZ regulations in Qatar are similar to the worldwide recommendations. The PZ practice in Al-Amal hospital abides by the regulations. Possible serious PZ drug-drug interactions, seizures, in hematologic cancer patients should be highlighted and carefully monitored.

Background: Despite the efficacy of IM in treating CML, high degree of resistance has already been noted.

AGP may reduce drug efficacy through its ability to interact with IM.

Objectives: Could the level of AGP be correlated with CML resistance/response to treatment and if it could be employed as a biological marker for CML resistance.

Methods: 25 CML patients were investigated for AGP level, serum samples were analysed to determine AGP level. Immunoturbidimetric assay is based on the formation of a precipitate of AGP with a specific antiserum. The mean, variance and significant difference between the means were determined using Student's t test and significance was determined when p value was ←0.05.

Results: Over 2 years a total of 89 serum samples were collected from 25 CML patients treated at Al Amal hospital in Qatar. Ten samples from 10 healthy volunteers were collected as a control group.

9 patients presented with CML at Chronic Phase (CP), 5 at Accelerated Phase (AP), 6 patients progressed while on treatment and five more patients were undergoing treatment and were at Complete Haematological Remission (CHR) at time of sample collection.

The mean AGP levels were 1.2 (±0.3), 1.61 (±0.4), 1.01 (±0.08), 1.07 (±0.09), and 0.72 (±0.04) for CP, AP, Poor Responders, CHR and controls respectively.

The mean AGP level for the control group was significantly lower when compared with any of the diseased group.

The significant differences amongst CP, AP, Poor Responders patients, CHR patients and control group were (p) 0.001, 0.03, 0.003, 0.005 respectively.

On the other hand, among these different CML groups there was no significant difference in AGP levels even when correlated with white blood cells, platelets and/or basophiles.

However, there was significant difference between CP and AP patients (P value 0.002) when AGP was correlated with WBC's.

Nonetheless AGP level could not be correlated with course of disease.

Conclusions: The noticed resistance in our CML patient population could not be correlated with AGP levels, as patients were responding or resisting treatment without any recognisable pattern of AGP; even when patients achieved CHR they might still had elevated AGP levels.

Back ground and Objectives: Vitamin D deficiency is very common in pregnant women and the current guidelines for vitamin D intake during pregnancy of 200-400 IU has been challenged recently .We conducted this study to determine the prevalence of Vitamin D deficiency among pregnant women and to evaluate the safety weekly oral 50,000 IU vitamin D supplementation for the mother and the newborn.

Setting and design: prospective study, at Hamad Medical Corporation, outpatient unit and delivery room.

Patients and Methods: 97 pregnant women were recruited in their first trimester between December 2007 and March 2010. Weekly oral vitamin D 50,000 IU were prescribed after an initial testing for serum level of 25-hydroxyvitaminD, parathyroid hormone, calcium, phosphorus, total protein and albumin. Other multivitamins supplementations were allowed during pregnancy. The same tests were repeated at each trimester. Umbilical cords Vitamin D levels were determined at birth. .

Results: Out of 97, 8 patients dropped out from the study for several reasons, and 19 patients had miscarriages.

Data were available for 97 women in the first trimester, 78 women in the second trimester and 61 women in the third trimester .The mean level of vitamin D in the first trimester and prior to starting vitamin D supplementation was 17.15ng/ml, 29.08 ng/ml in the second trimester, 27.3 ng/ml in third trimester and 22.36 ng/ml in newborns. There were no toxic levels of vitamin D in any of the women at second or third trimester or in the newborns. The mean levels of vitamin D in the second and third trimester were not significantly different in the women who were taking multivitamin supplementation versus those who were not.

Conclusion: Weekly dose of 50,000 vitamin D during pregnancy is safe in our population, maintains acceptable vitamin D level during pregnancy and the newborns' vitamin D level correlates with the mother's levels.

Background: Vitamin B12 (vit B12) deficiency is one of the major causes of megaloblastic anaemia and should be avoided as early as possible since a supplementation of mother and child can prevent neurological symptoms of the baby. Furthermore, the neurological symptoms of affected children are (partially) reversible. Elevated methylmalonic acid in urine and homocysteine (Hcy) in plasma are sensitive indicators. In the State of Qatar, extended newborn screening of classical homocystinuria was realized for all 73,994 neonates in last 4.5 years. Newborns with slightly elevated Hcy levels in dried blood spots (DBS) were followed up with regard to possible vit B12 deficiency. In addition, the propionylcarnitine (C3) levels were analysed.

Methods: Determination of Hcy in DBS was performed using liquid chromatography electrospray tandem mass spectrometry. C3 levels were obtained from general newborn screening. The vit B12 levels in plasma were analysed spectrophotometrically.

Results: In all, 117 cases with mildly elevated Hcy levels were found. 65 were diagnosed with vit B12 deficiency. Only 9 of these 65 newborns had abnormal C3 levels. No correlation was found in this group between Hcy and C3 levels.

Conclusion: Extended neonatal screening of Hcy is a useful tool for early diagnosis and treatment of vit B12 deficiency.

Background: Although open Ramsted's pyloromyotomy is the gold standard for the surgical management of infantile hypertrophic pyloric stenosis, laparoscopic pyloromyotomy has been found highly successful. Various factors, however, can affect the outcomes of surgical interventions in these patients. We observed a relationship between the number of ports used and outcome in patients undergoing laparoscopic pyloromyotomies.

Method: We retrospectively assessed the medical records of selected group of patients who underwent laparoscopic pyloromyotomy in our institution. Factors analyzed included operation time, length of hospital stay, postoperative complications, and time to postoperative full feeding.

Results: We observed failure of myotomy in both two patients who underwent laparoscopic pyloromyotomy using only two working ports compared to successful myotomies in the remaining patients.

Conclusion: Laparoscopy provides good results in terms of intraoperative exposure and cosmesis. However, standardized surgical technique with two working ports is advisable and this can trigger further research to be ascertained.

Population aging is a worldwide phenomenon, but its impact on Qatar is unique. The proposed system aims at comprehensive and integrated vital signs (ECG, Saturation of Arterial Oxygen (SpO2), BP and Heart rate (HR)) monitoring using a wearable sensor platform without professional involvements or interfering the elderly's everyday activities. A novel wireless physiological sensor node with single highly-integrated board has been specifically designed and fabricated ( Fig.1(a) ). The new board comprises of a MCU, ECG analog front-end, LED driver and brightness adjustment circuit for photoplethysmograph (PPG) measurement, a CC2420 chip for wireless communication and a FTDI FT232RL chip for MCU programming and real-time debugging. A miniaturized wireless gateway was also designed ( Fig.1(b) ) to wirelessly receive the data from sensor node and further relay to the PC for ongoing research on ECG denoising and arrhythmia classification.

A novel MEMS-based electrode has been designed and fabricated for ECG measurement as shown in Fig.2 . Compared with conventional ECG electrodes, micromachined electrode is more comfortable; no direct contact of gel with the human skin and imposes no side effects to human for continuous and long term measurement. A unique characteristic feature of the proposed electrode is that the microneedle array is made of heavily doped silicon, which is electrically conductive and eliminates the requirement to dope Ag/AgCl or metal layer on the microneedles for electric contact. The microneedles can directly pierce through the outer skin surface, lowering the electrode-skin-electrode impedance (ESEI) and eliminating the need for skin preparation which, is prerequisite for wet electrode. For long-term monitoring, mechanical failure of micro-needles may accidentally happen due to the axial loading during insertion process or transverse loading during the measurement. As a result, the broken silicon needles will become debris in the skin, which attracts healthy concern for the user. Therefore, critical buckling loads for fabricated micro-needle were investigated using both theoretical estimation and ANSYS simulation. The results show that the critical buckling load is much larger than theoretical insertion force thereby the buckling problem will not occur during the insertion process.

This work is supported by Qatar National Research Funding (QNRF) under the grant NPRP 09-292-2-113.

Background: X-linked diseases are single gene disorders that are due to the presence of mutations in genes that reside on the X chromosome. X-linked recessive disorders are predicted from the family structure, where only boys are affected and there is no father to son transmission of the mutant allele. Heterozygous females are usually non-symptomatic carriers but can manifest a milder form of the disease. The identification of the genetic defect in X-linked disorders facilitates the diagnosis of affected individuals, aid in providing informative counseling and may help in prenatal diagnosis. Objectives: The study aims at mapping and identification of one gene responsible for congenital cataract and micropthalmia in a three-generation family.

Methods: We recruited 12 members of a family with a clear X-linked pattern of inheritance with three affected males, all showing congenital cataracts and microphthalmia. Gene mapping was attempted using a set of microsatellite markers selected to cover the whole X chromosome. Haplotypes were generated for all genotypes and the haplotypes were examined for alleles shared by the affected males and not shared by the unaffected males. Once the region of linkage was identified, we examined a few candidate genes by mutation analysis by resequencing in forward and reverse of one affected individual, one obligate carrier and one unrelated normal control. Candidate genes were chosen from the human genome public databases and were selected based on the possibility that they play a role in eye development or are expressed in fetal eyes.

Results: The region of linkage is a 50 Mb in the pericentromeric region of the X chromosome (Xp21.1-q21.2). The candidate genes ARR3, DACH2 and BCOR were resequenced in forward and reverse, but no variations were detected.

Conclusions: We were capable of mapping the gene responsible for congenital cataracts and microphthalmia to the pericentromeric region of the X chromosome. We examined 3 candidate genes but no variations were detected. Currently, we are examining other candidate genes. If no mutant alleles are identified by this candidate gene approach, we will proceed by performing whole exome sequencing of the X chromosome (after enrichment) utilizing the next generation sequencing technology.

Background: Autosomal recessive diseases are considered as a major group of single-gene disorders among Arab population. We have recruited a family with three siblings with a mental retardation (MR) syndrome who were born to consanguineous Qatari parents. The clinical problems comprised significant mental retardation, microsomia, signs of skeletal dysplasia, and thoracolumbar kyphosis. The oldest patient suffers also from epileptic seizures. Also, the parents and the other three of their six children are healthy. Causative genes and mapping strategy focused on large genomic regions demonstrating homozygosity in all of the affected individuals.

Objectives: Our goal is to identify the genetic causes of undelineated autosomal recessive disorders among Arab families.

Methods: Whole genome genotyping has been performed by (Illumina 300Kb SNPs). Followed by homozygosity mapping and linkage analysis. In addition, targeted resequencing of the candidate genes within the linked homozygous loci was performed.

Results and conclusions: Homozygosity mapping revealed a single large shared region of homozygous SNPs on the long arm of chromosome 4 flanked by rs28419770 (4q13.1) and rs4105671 (4q21.23). This block contains more than 120 genes, none of which has been implicated in MR or any of the above mentioned phenotype so far. Sequencing of candidate genes within the region revealed two novel missense variations in FRAS1 gene; an Arg3099Gln and Thr3149Met. Both variations were found in the three affected siblings in homozygous status, while the parents were heterozygous. Furthermore, these two variations have not been found in 140 individual controls in homozygous pattern, however, a heterozygous pattern of variations were found in three individuals only. Our future plan will be doing the whole exome sequencing for the shared region using next generation sequencing platform.

Prevalence rate of autism-spectrum disorders (ASD) in Qatar is uncertain, and speculation that their incidence is increasing continues to cause concern. Although the apparent increased prevalence of autism may reflect improved detection and recognition of autism and its variants. No comprehensive survey has been done to estimate the prevalence of autism in Qatar.

The target population for this study is children aged 3 through 18 years whose parents resided in Qatar.

Children with ASD in Qatar going to be identified using a two-phase process.

In Phase 1, children from a representative sample of all primary schools in Qatar going to be preliminarily screened using Social Communications Questionnaires, and those who are suspected to have ASD will be approached through phase 2. Review of records of children with possible ASD from the following institutions:

1). Shafallah Center for children with special needs records, which includes all children with preliminary diagnosis of ASD, who attends special classes for autism.

2). Other centers and school which has similar facilities.

3). Records from the Supreme Council of Health, Hamad Medical Corporation, and any other health centers.

In Phase 2, clinical evaluation is conducted by a developmental psychologist, and/or paediatrician. It includes a medical, developmental, and behavioural history; a standard physical and neurologic examination, In addition, the Autism Diagnostic Interview (ADI-R), and Autism Diagnostic Observation Schedule-G (ADOS-G) will be administered.

Preliminary analysis of 179 subjects showed the highest prevalence among age group 7–14 years (61%).

Male/female ratio was 82% /18%, which is around 5/1. Further works needed to calculate the total prevalence rate. Obtaining a reliable estimate is important in planning for providing the best health care and educational services needed to improve the overall outcome of autism.

Background: The number of genes identified to be responsible for autosomal dominant genetic conditions far exceeds those identified for autosomal recessive conditions. This is expected because autosomal recessive disorders are rare and a single large family or a large number of smaller families are needed for gene mapping and identification. However, this hurdle can be overcome by homozygosity mapping utilizing inbred families.

Objectives: The aim of this study is to map loci and identify genes that play a role in autosomal recessive disorders among Arab families and to examine their role with the final aim of outlining novel genes and pathways. The investigation capitalizes on utilizing large inbred families, as well as smaller inbred families, by employing homozygosity approaches for mapping the etiologic genes.

Methods: It includes the recruitment of families and obtaining detailed clinical, genealogical and genotypic data. Families with pedigrees that provide suggestive evidence of autosomal recessive mode of inheritance and with consanguinity are selected. Homozygosity mapping is done by genome wide SNP genotyping using dense chips, followed by linkage analysis.

Results: We performed homozygosity mapping on one recruited family to seek a region of homozygosity shared by affected individuals. This family includes eight individuals from 4 related sibships in an extended Palestinian family who suffer from congenital cataract. Homozygosity mapping revealed a region flanked by rs4276160 (3p22.1) and rs749512 (3p21.31) on the short arm of chromosme 3. This interval contains 92 genes, none of which has been implicated in eye disease. Further investigation for this family is currently underway using whole exome sequencing to identify the causative gene mutation. Other examples will be presented.

Conclusion: Homozygosity mapping utilizing inbred families is a very powerful tool for gene mapping in autosomal recessive families. However, the region of linkage is usually big and contains a large number of genes, which is prohibitive with the classic technology. Genomic approaches such as whole exome sequencing is yet another powerful tool to overcome this hurdle.

In Qatar, cardiovascular diseases are the leading cause of mortality and morbidity.

Cardiovascular diseases can be prevented and controlled by modifying lifestyle risk behaviours such as physical inactivity, unhealthy diet and smoking. Obesity as the result of physical inactivity and unhealthy diet raises the risk of heart diseases. Studies show that 62.6% of Qatari women were overweight and the prevalence of overweight is high among adult females with 80% of women 30 years and over. Qatar World Health Survey in 2006 shows that only 40% of Qatari women participated regularly in sports or other physical activities. Furthermore, waterpipe smoking is increasing across the Eastern Mediterranean.

Funded by the Qatar National Research Fund, the ultimate goal of this study was to find ways to effectively promote cardiovascular/coronary artery disease prevention and management activities among Qatari women (citizen and resident Arabic women) by exploring factors affecting the ways in which Qatari women participate in physical activities, healthy diet and smoking.

An exploratory qualitative research approach was used in this study, with a semi-structured questionnaire using open ended questions to gather data. Individual in-depth interviews were conducted with 50 Arabic women who are 30 years and over, have confirmed diagnosis of CVD/coronary artery diseases to investigate factors influence lifestyle risk behaviours associated with cardiovascular diseases amongst Qatari women (citizen and resident Arabic women).

The study's results show that social support networks; cultural beliefs, values, practices, and religion; rapid economic growth; changing environmental and social conditions influence women's participation on physical activities, dietary practices and smoking. Conclusion: Prevention of cardiovascular diseases and promotion of healthy lifestyle should consider women's specific health condition and socio-economic status; empower women to take charge of their health; facilitate women's informal and formal social support networks; provide culturally appropriate public education; create healthy environment with more recreational facilities for women and children.

Background: Genetic and environmental factors are highly related with gestational diabetes mellitus (GDM) and type 2 diabetes (T2D). Our objective was to explore whether some genetic variants such as rs12255372, rs7903146 of TCF7L2 gene are significantly associated with the risk of gestational diabetes mellitus among Arabian population.

Methods: A case control study was designed for such genetic association study. A total of 159 unrelated pregnant women (114 Arab; 40 gestational diabetes mellitus cases and 74 controls and 45 non-Arab; 11 gestational diabetes mellitus and 34 controls) were recruited from antenatal care unit of HMC. Blood sample were drawn for DNA extraction, then genotyped for TCF7L2 gene variants (rs12255372, and rs7903146) using TaqMan real time PCR assay. Plasma was used for biochemical analysis including glucose, insulin and adiponectin.

Results: The CC, CT and TT genotype frequencies of the TCF7L2 rs7903146 variants was not significantly different between the control and gestational diabetes mellitus cases (39.4%, 50,0%, 10.6% vs. 40.6%, 43.8%, and 15.6%, p=0.444) among Arab populations, respectively. Only, the T allele of rs12255372 variant was significantly associated with risk of gestational diabetes mellitus with odds ratio of 2.370, (95% of CI 1.010–5.563) with the p value of 0.047 among Arab subjects using the genetic dominant model after adjustment of BMI and age. The other polymorphism rs7903146 was not significantly associated with GDM among Arab and non-Arab subjects. No significant difference was observed for glucose, insulin and adiponectin hormone after 50g glucose load by genotyping of both variants.

Conclusion: The TCF7L2 rs12255372 variant is associated with an increased risk of gestational diabetes mellitus in Arab women. Further studies are needed with larger sample sizes.

Background: Caring for a child diagnosed with autism is strongly linked to maternal caregiving burden. It forces family members to modify their daily lives to suit their different reality and it imposes social, psychological, and economical hardships. No previous research has assessed the burden associated with caring for a child with autism on the lives of caregivers in Qatar or the Gulf country region.

Objective: To assess the burden of autism on the lives of caregivers of children with autism in Qatar.

Methods: Two groups of caregivers of children between 3 to 17 years old were recruited. The caregivers of children with autism (Autistic Group, or AG) were recruited from two developmental pediatric and children rehabilitation clinics in Qatar. The caregivers of typically-growing children (Non-Autistic Group, or NAG) were recruited during their visit for a family clinic of a primary health care facility for routine medical check-up. Data collected from both groups included demographic information of caregivers and children and several questions aimed at assessing the burden of caring for a child with autism. Items in questions were developed after a thorough literature review.

Results: Children in the AG spent more time indoors, watching television, or sleeping than children in the NAG (p=0.05). Around 50% of the caregivers in AG did not wish to answer questions about whether they would encourage their children to get married or become parents when they grow up. Half of the sample in the AG utilizes special education classes and other facilities, and the remaining half has access problems. Religious faith helps the majority of caregivers in coping with the burden associated with caring for a child with autism.

Conclusions: This study provided evidence for the impact of caring for a child with autism on the life of the caregivers. It also gave an insight into areas relating to support provided to children with autism and their caregivers and the status of the children with autism in different aspects. The findings should help health policy-makers provide better and more focused supports to the children with autism and their families.

Background: Pineal hormone melatonin (MEL) is a versatile molecule with diverse physiological roles ranging from circadian entrainment to anti-cancer effects. Clinical trials indicated that a co-application of cisplatin and melatonin improved the 1-year survival rate. Also, Futugami (2001) claimed melatonin enhances the sensitivity of an ovarian cancer cell line to cisplatin.

Objective: Here we study the anti-cancer effects of a co-application of cisplatin (CDDP, 1pM -10 mM - log10 scale) and melatonin (1pM – 100μM) on MCF-7 cells.

Methods: Cell viability was assessed through MTT assays and trypan blue exclusion tests.

Results: 1) a) CDDP causes concentration-dependent growth inhibition of MCF-7 cells at high concentrations (1–100 μM) over 24 and 48 hrs with an IC50 of 99.6 ± 5μM (24 hrs) b) Over a period of 6 days, 1uM CDDP causes significant (52.35 ± 0.64% of control) growth inhibition 2) MEL does not significantly inhibit MCF-7 cell growth over 24 hr and 6 day time points. 3) Simultaneous co-application of MEL with CDDP significantly (p ← 0.05) reverses 80?M CDDP induced growth inhibition over 24 hrs at physiological concentrations (0.1 – 10nM) (increase in growth by 21.4 ±} 1.8 %). 4) However, simultaneous co-application of MEL and CDDP does not significantly reverse the growth inhibition induced by 1μM CDDP over 6 days.

Conclusion: As reported by several labs, CDDP shows significant growth inhibition within 24 hrs only at high concentrations while long term growth inhibition is observed at low concentrations (1–10μM). The results indicate that the sub clone of MCF-7 cells used by us is melatonin “insensitive” as MEL does not have an anti-proliferative effect over the points tested. However, these cells are not completely irresponsive to MEL as MEL reverses CDDP induced growth inhibition at physiological concentrations. The question arises as to why such a “protection” is observed only at physiological concentrations. Moreover, this effect is only observed when acute cell death is induced at high concentrations and not at chronic low concentrations. To conclude, the results open up the interesting questions of the molecular basis of the protective effects of melatonin on CDDP induced cell death and melatonin “insensitivity”.

This study was carried out to examine the difference between the respiratory volumes in athlete and non-athlete adolescent females, how does exercise affect the respiratory volumes and how could the effects of exercise on the respiratory system affect the heart rate? Introduction: The respiratory and circulatory systems are the most important systems in the body as they involve vital organs (lungs and heart). They are affected by several factors, which may improve or weaken their function. Exercise positively affects their function. Methods: In this study 2 groups were compared: athletic and non-athletic females using a spirometer to measure the respiratory volumes before and after running. The heart rate and blood pressure were also measured in both groups. The statistical analysis and graphs were done using excel 2007. Results: The pre-test mean vital capacity in non-athletes was 2600.0± 496.7 and in athletes: 2642.9 ± 340.9. Whereas post-test mean vital capacity of lungs in non-athletes was 2385.7 ±429.8 and in athletes: 2428.6 ±407.1. Pre-test mean blood pressure in non-Athletes was 94.6 ± 9.3mmHg and in athletes was 86 ± 8.1 mmHg but post-test mean blood pressure in non-athletes was 113.8 ± 31.6 mmHg and in athletes: 99.1 ± 8.8 mmHg. The pretest mean heart rate in non-athletes was 89±5.2 beat per min while in the athletes it was 86 ± 6.5 beat per min. Conclusion: On the short term exercise increases the heart rate, decreases the blood pressure, decreases the lung capacity and increases tidal volume. Whereas long term effects involve increased lung capacity and tidal volume; and decreased blood pressure and heart rate.

The coagulation/fibrinolytic system controls the intravascular fibrin homeostasis; in addition to participating in a wide variety of physio-pathological processes. The components of the system have an influence on tumor metastasis, growth and invasion. This is a result of their involvement in tumor matrix construction, angiogenesis and cell migration.

Thrombosis of unexplained etiology among healthy and cancer patients; is a major cause of death. Several homeostatic markers are currently used to predict the advent of thrombosis. However, none of these markers directly indicate the course and progression of the disease; thus thrombosis remains unexplained.

Endothelial Protein C Receptor EPCR gene carries 13 single nucleotide polymorphisms, which define 3 haplotypes: A1, A2 and A3. One of these, A3, encodes a protein, which is more sensitive than the other two in shedding enzymes. High levels of protein C are determined by PROCR haplotype 3. A3 haplotype reflects a high soluble Endothelial Protein C Receptor (sEPCR) level. Therfore, it is a candidate risk factor for venous thrombosis. We observed that the plasma concentration of sEPCR in cancer patients was much higher than that observed in controls. We suggest that sEPCR released from malignant cells could serve as a “trap” for protein C, preventing it's binding to EPCR on the surface of endothelial cells and induced thrombotic state.

We developed a method, based on activated Partial Thromboplastin Time, in order to analyze the ability of (EPCR) on the cancer cell membrane to trap circulating Activated Protein C (APC). This test is in conjunction with other specific tests used for assessing thrombotic state, such as the one to quantitate soluble fibrin and d-dimer.

Previous study of lung cancer patients, done by Department of Pathology, Free University Medical Center 2002, revealed a marked association between high EPCR levels; and poor survival or relapse in patients with stage I lung adenocarcinoma. The aim of our study is to investigate the role of sEPCR as a cause of thrombotic disorder, among cancer patients. Furthermore, to detect whether EPCR of cancer cells is haplotype 3, that affect on the level of sEPCR.

Perfusion-decellularized native lungs seeded with human BJ

RNA-induced pluripotent stem (BJ-RiPS) and umbilical vein endothelial cells failed to regenerate functional lung tissue as quantified by immunohistochemistry (no detection of TTF1,CC10,and Pro-SPB), gene expression (non-significant differences in lung-specific gene expression as compared to cells cultured under standard conditions), and in vitro lung gas exchange properties. Histological analysis of orthotopically transplanted BJ-RiPS lungs revealed a teratoma (detection of ectoderm: TuJ1, mesoderm: SMA, and endoderm: TTF1).

The prevalence of type 2 diabetes mellitus (T2D) is increasing rapidly worldwide with figures being projected to reach 700 million and 366 million by 2030 respectively, according to the recent reports by the World Health Organization 2010 and the International Diabetes Federation 2010. T2D development has been shown to be driven by both environmental and genetic factors.

Consanguinity among Middle-Eastern population, especially the Gulf region, has proved to play a major role in predisposing to multiple hereditary conditions such as cancer, hypertension, and T2D, the latter showing a moderately high prevalence (16.7%) among Qataris.

In this study we aim to identify novel genetic variants and clarify new molecular pathways of T2D in the Qatari population. We will take the advantage of the advanced technologies in genome wide scan and next generation sequencing to investigate a large three generation Qatari family with a history of early onset T2D for the initial stage of the study. More consanguineous families will be recruited for this project and will undergo the same investigational steps in order to identify shared novel mutations between the different family members.

To date, several approaches, such as candidate gene studies, linkage analysis, and genome-wide association studies (GWAS) have been used to identify genetic variants involved in the pathophysiology of T2D and glucose homeostasis. Among these, GWAS has been the most successful approach at the moment to uncovering common genetic variants involved in the disease susceptibility. Next generation whole exome sequencing is a new promising approach to gather novel insights into genes and pathways involved in T2D susceptibility, also allowing the discovery of potential rare mutations.

This study will use next generation sequencing technology to discover potential causative mutations segregating in diabetic inbred Qatari families, and possibly relevant to the Qatari population.

Chronic stress is a leading risk factor for heart diseases, diabetes, asthma and depression. However, physicians find it difficult to continuously track a person's stress levels throughout the day, as current techniques of electrocardiogram and blood pressure monitoring are not practical. There is thus a critical need for a non-invasive, ambulatory device to track physiological stress over extended periods of time. Such information would allow physicians to assess precisely the affect of stress and determine the most appropriate interventions.

The primary objective of this study was to investigate the relationship between non-invasive, physiological signal parameters and the stress level as perceived by the subject. The mapping of physiological parameters onto stress levels to accurately monitor the stress levels in a subject under various conditions will assist the diagnosis of subjects at risk of various stress related disorders.

An ambulatory, wireless device was developed with respiratory rate, galvanic skin response and heart rate sensors, which the subjects can wear comfortably while performing their everyday tasks. An experiment involving 13 activities with different stress levels was conducted on 22 subjects during which physiological data was collected using the developed device. While participating in the experiment, subjects had to record the stress level of each activity on a scale of 1 and 7. The data collected was processed in MATLAB, appropriate signal parameters extracted and then correlated with the subject's perceived stress levels.

Analysis of the data showed that the stress levels varied as the subjects progressed into different activities due to their varying current mental states. The perceived nature of stress varied considerably amongst the individuals with certain activities able to induce a stronger variation in stress compared to others. The derived features were shown to be effective in tracking the variation in stress induced in the subjects.

Results of the experiment showed that the developed device was effective in recording non-invasive physiological for use in tracking the stress levels and mental state of the subjects. Further work is being done to develop an effective model that accurately predicts stress levels based on the physiological data collected.

Three-dimensional (3D) videos are getting quite popular, and equipment for recording and processing them are becoming affordable. Creating 3D videos is expensive. Thus, protecting 3D videos against illegal copying is an important problem. We present a novel system for finding 3D video copies. Our system also identifies the location of the copied part in the reference video. The system can be used, for example, by video content owners, video hosting sites, and third-party companies to find illegally copied 3D videos. To the best of our knowledge, this is the first complete 3D video copy detection system in the literature.

Detecting 3D video copies is a challenging problem. First, comparing numerous numbers of frames from potential copies against reference videos is computationally intensive. Second, many modifications occur on copied videos; some of them are intentional to avoid detection and others are side effects of the copying process. For example, a copied video can be scaled, rotated, cropped, transcoded to a lower bit rate, or embedded into another video. The contrast, brightness, and colors of a video can also be manipulated. Furthermore, 3D videos come in various encoding formats, including stereo, multiview, video plus depth, and multiview plus depth. Changing the format is possible during copying, which complicates the detection process. Finally, new views can be synthesized from existing ones. These views display the scene from different angles, and thus reveal different information than in original views. For example, an object occluded in one view could appear in another.

We implemented the proposed system and evaluated its performance using many 3D videos. We created a large set of query videos with 284 videos to represent all practical scenarios. Our results show that the proposed system achieves high precision and recall values in all scenarios. Specifically, our system results in 100% precision and recall when copied videos are unmodified parts of original videos, and it produces more than 90% precision and recall when copied videos are subjected to various transformations. Even in extreme cases where each video is subjected to five different transformations, our system yields more than 75% precision and recall.

Mobile devices such as smart-phones and tablets are becoming ubiquitous, with ever increasing communication capabilities. In situations where the necessary infrastructure is unavailable, costly, or overloaded, opportunistically connecting theses devices becomes a challenging area of research. Data is disseminated using nodes that store-carry-and-forward messages across the network. In such networks, node cooperation is fundamental for the message delivery process. Therefore, the lack of node cooperation (e.g., a node may refuse to act as a relay and settle for sending and receiving its own data) causes considerable degradation in the network. In order to ensure node cooperation in such networks, we investigate three main challenges: (i) ensuring fair resource utilization among participating mobile devices, (ii) enabling trustful communication between users, and (iii) guaranteeing scalable solutions for large number of devices.

(i) Fairness is particularly important for mobile opportunistic networks since it acts as a major incentive for node cooperation. We propose and evaluate FOG - a real-time distributed framework that ensures efficiency-fairness trade-off for users participating in the opportunistic network.

(ii) Since users may not accept to forward messages in opportunistic networks without incentives, we introduce a set of trust-based filters to provide the user with an option of choosing trustworthy nodes in coordination with personal preferences, location priorities, contextual information, or encounter-based keys.

(iii) Mobile opportunistic solutions should scale to large networks. Our hypothesis is that in large-scale networks, mobile-to-mobile communication has its limitations. We therefore introduce CAF, a Community Aware Forwarding framework, which can easily be integrated with most state-of-the-art algorithms, in order to improve their performance in large-scale networks. CAF uses social information to break down the network into sub-communities, and forward message within and across sub-communities.

In the three contributions we propose above, we adopt a real-trace driven approach to study, analyze, and validate our algorithms and frameworks. Our analysis is based on different mobility traces including the San Francisco taxicab trace, traces collected from conferences such as Infocom’06 and CoNext’07, and Dartmouth campus wireless data set.