Qatar Foundation Annual Research Forum Volume 2012 Issue 1

Collagen fibers are essential components of tissues and an important protein in the extracellular matrix, which maintains the structural and mechanical integrity of tissues while providing key signals to regulate cell functions. Although animal-based collagens can be used as biomaterial for tissue engineering heart valves, they cause infections and lack flexibility. These limitations have stimulated the exploration of collagen mimetic peptides (CMPs) through a bottom-up approach using computational modeling followed by experiments. Here, a 3D-structure of 3-helices of CMP was used to model the new CMPs to identify its structural stability and hotspots. These data assist in introducing charged residues by mutations to cross-link 3-helices and to add binding motif (GFOGER) for integrin in the CMP structures. The helical stability and self-association of the mutated CMPs have been validated using molecular dynamics (MD) simulations, surface electrostatic calculation followed by biochemical experiments using HPLC and mass spectrometry. The modelling analyses indicated that the CMPs show the desired structural properties for self-assembly and high affinity towards integrin binding. The introduction of the charged residues increased the possibilities for helical cross-link (gelation). The results suggest that altering the positions and length of hydrophobic repeats (GPO) of CMPs could improve thermal stability (Figure). The structural properties of the modelled CMPs were reproduced in experimental conditions. Our study provides potential peptide candidates that promise to show some inherent structural properties of native collagen in silico and in vitro. These properties are required to produce functional scaffolds for tissue engineering heart valves.

Our strategy for heart valve tissue engineering uses autologous cells to populate appropriate template matrices.The goal is to create a suitable scaffold supporting proper cell growth while reproducing the specific mechanical properties of native heart valves extracellular matrix (ECM). Accordingly, aligned and non-aligned nanofibrillar structures of different porosities were prepared and evaluated with regards to their mechanical properties and their ability to support human adipose derived stem cell (hADSC) colonization and growth. Nanofibrillar structures were obtained by jet-spraying poly (ε-caprolactone) dissolved in chloroform at different concentrations (0.0733, 0.0833 and 0.1033 mg/ml). Morphological evaluations of the structures were performed using scanning electron microscopy and porosity calculated. hADSCs (600,000) were top and rotary seeded on nanofibrillar discs (diameter 1 cm and thickness 0.8 mm) and cultured in 10 ml of complete medium under rotation (10 rpm) for 20 days. Histology (DAPI staining) and DNA quantification characterized the resulting cellularized structures. Jet-spraying polymers resulted in biphasic structures composed of both a dense and a nanofibrillar layer (Fig. 1-A). The nanofibers could either be of random orientation (isotropic) or well aligned (anisotropic). Isotropic matrices showed an increase in porosity when increasing polymer solution (96 to 97 %). Mechanical properties were inversely related to matrice porosities. Anisotropic matrices were stiffer than isotropic ones (elastic modulus up to 22 and 2 MPa respectively). hADSC proliferated significantly over 20 days within the scaffolds (up to 5-fold DNA increase), regardless of structure and porosity. The constructs dense polymer layer was favored by the cells up to 10 culture days, but after 20 days, the cells tended to bridge the entire scaffolds thicknesses (Fig. 1-B). This study highlights the potential of biphasic nanofibrillar matrices as substrate for valve engineering, particularly with regards to their elevated mechanical properties and capacity to support cellular population and proliferation.

Background & Objectives: School children among the most vulnerable groups that pass critical periods of physical, mental, and developmental growth are in need of special nutrition and health care. Little is known about the nutritional status of school children in Qatar. The aim of the present investigation is to determine the anthropometrics measurements (height, weight and body mass index) of Qatari school children, comparing the study results with the international reference population and to determine the relationship between obesity and lifestyle. Methods: Study was conducted on a sample from Qatari school children. A representative sample (1500 children) were selected between the ages of 6-12 from 23 schools using multistage cluster random sample, while 200 cases from each age group were targeted as primary sampling unit. Data about number of physical education classes, hours of physical activity per week, and information about the sedentary life style were obtained by utilizing a standardized self-administered questionnaire. Results: The current results showed that the percentage of body weight for Qatari children were significantly higher than the reference values while their body height percentage were significantly lower than the reference. Using the WHO (2007) classification of BMI for children, 8%, 16% and 23% of studied children had thinness, overweight and obesity, respectively. The majority of children (55.1%) spent more than 2 hours daily watching TV, surfing the internet or playing electronic games, 25.8% didn't report any kind of physical activity and 48.8% had physical activity less than one hour/day. The current study showed that there is a significant relationship between children's physical activity and prevalence of overweight and obesity. Conclusions: The current work looks at school children in Qatar to create a more complete picture of the current state of health and help to determine how lifestyle and environmental changes can be mitigated as a causal factor of obesity and therefore lifelong poor health.

Objectives: Although predictors of mortality have been identified in major atrial fibrillation (AF) clinical trials, most of the data were limited to studies in the developed world and included mainly Caucasian patients. The aim of this study is to identify predictors of mortality in Middle Eastern Arab and South Asian patients hospitalized with AF in a real-world population in a Middle Eastern country. Methods: Retrospective analysis of prospective registry of all patients hospitalized with AF in Qatar from 1991 through 2010 was made. Ethnicity, clinical characteristics and co-morbidities were analyzed in relation to mortality. Results: During the 20 year period; 2857 Arabs and 548 Asians were hospitalized for AF. There were 138 deaths among Arabs and 14 among Asians (4.8% versus 2.6%, p= 0.02). Multivariate analysis of predictors of in-hospital mortality identified chronic renal impairment and acute coronary syndromes as independent predictors of poor outcome among patients hospitalized with AF whereas ethnicity was not [Table]. Conclusions: In this region, the risk of in-hospital mortality for patients hospitalized with AF remains increased in patients who have chronic renal impairment or acute coronary syndromes irrespective of ethnicity. Patients at high risk may benefit from aggressive monitoring and intervention in order to reduce mortality.

Introduction: Obesity is a global problem affecting adolescents and teens with profound psychological and medical sequelae. The role of bariatric surgery in adolescents remains controversial. The aim of the study is to report our results with sleeve gastrectomy in this population. Goal of study: To study the efficacy of sleeve gastrectomy as a treatment for obese adolescents in terms of weight loss, comorbidity resolution and safety of procedure. Methods: Retrospective review of our records of all patients under the age of 19 who underwent laparoscopic sleeve gastrectomy in Hamad General Hospital in the years 2010-2012. Variables studied included; age, BMI, preoperative and postoperative weight, sex, comorbidities, length of stay, operative time, and early or late onset complications. Results: Out of 700 patients from our institute, 37 patients (5%) were adolescents. 45% males N=17 and 55% females N=20. Mean age was 17 ±1.5. Mean length of stay was 3.6 ±0.8. Mean operative time was 64 ±17 minute. Mean preoperative weight 141 ±27 kgs (200-94.) Mean BMI 51±8.8 kg/m2 (72-35). With regard to comorbidities, one person had obstructive sleep apnea and reported resolution. Mean follow up was 8 months (17-1), mean post op BMI 38 ±11.8 kg/m2 (23-70), mean excess weight loss -28% (4-45%). Mortality 0%. Morbidity 0%. Conclusion: Laparoscopic sleeve gastrectomy is a safe option for treatment of obese adolescents. It is particularly effective in this particular group with satisfactory safety profile and adequate weight loss. However, longer follow up is needed to evaluate the long term effects of the surgery.

Objectives: Little is known about the ethnic variability in trends of the etiologies of atrial fibrillation (AF) and related mortality. This was examined in this study in patients hospitalized with AF in a real-world population in a Middle Eastern country. Methods: Retrospective analysis of prospective registry of all patients hospitalized with AF in Qatar from 1991 through 2010 was made. Rates and trends of clinical characteristics, cardiac comorbidities and in-hospital mortality were analyzed according to ethnicity. Results: During the 20-year period; 2857 Arabs and 548 Asians were hospitalized for AF. Arabs were 9 years older and more likely to have hypertension, diabetes mellitus, chronic renal impairment and dyslipidemia compared to Asians. Valvular heart disease and acute coronary syndromes were more common among Asians while congestive heart failure was more common in Arabs. Overall in-hospital mortality was lower for Asians compared to Arabs while stroke rates were comparable [Table1]. There was an increase in the prevalence of diabetes mellitus and hypertension in both groups in the latter years of the study period but, more so in Arabs when compared to patients hospitalized in the earlier years. Associated valvular heart disease was trending lower in both groups while ischemic heart disease prevalence was trending higher with no significant differences between the two groups. Rheumatic heart disease was statistically trending lower in prevalence; however it remained more prevalent among Asian patients over the study period. There were no significant differences in mortality trends over the study period between the two groups [Table 2]. Conclusions: The current study is the first ever report of comparative ethnic trends in etiologies and outcome of AF among Middle Eastern Arab and South Asian patients over a 20-year period. The current study underscores the need to study differences in atrial fibrillation among various ethnicities.

Background and Objectives: Most previous explanations of fatigue during repeated sprint exercise have focused on muscular factors associated with cellular mechanisms. At present, the nature of the neural adjustments and the extent to which corticospinal responsiveness is altered after the completion of repeated sprint exercise are yet to be elucidated. This study was undertaken to test the hypothesis that, in addition to the large peripheral fatigue, supraspinal factors would contribute substantially to neuromuscular adjustments of the quadriceps muscle in response to a repeated sprint cycling exercise. Methods: Twelve active individuals performed 10 x 6-s 'all out' sprints on a cycle ergometer (recovery= 30 s), followed 6 min latter by 5 x 6-s sprints (recovery= 30 s). Surface electromyographic activity was continuously recorded during the exercise. In addition, transcranial magnetic and electrical femoral nerve stimulations during brief (5-s) and sustained (30-s) isometric contractions of the knee extensors were performed before and 3 min post-exercise. Results: Peak power output and vastus lateralis root mean square activity decreased across sprint repetitions (P <0.001). These decrements were significantly (r= 0.89; P <0.001) correlated. Maximal strength of the knee extensors decreased during brief and sustained contractions (∼11% and 9%, respectively; P <0.001). Cortical voluntary activation values (∼90%), motor evoked potential amplitude and silent period duration responses measured during briefs contractions were unaltered. While cortical voluntary activation declined (P <0.01) during the sustained maximal contraction in both test sessions, larger reductions occurred (P <0.05) after exercise. Lastly, resting twitch amplitude in response to both femoral nerve and cortical stimulation was largely reduced (>40%, P <0.001) following exercise. Conclusion: The novel findings provided by motor cortex stimulation are that exercise induced reductions in cortical voluntary activation were seen in sustained, but not brief, maximal isometric contractions of the knee extensors. This, along with the lack of corticospinal responsiveness impairment from pre- to post-exercise, indicates that supraspinal processes do not necessarily limit repeated sprint ability. Rather, fatigue exhibited by the quadriceps when cycling sprints are repeated resides within the muscle itself, due to limitations in energy supply and/or the intramuscular accumulation of metabolic by-products.

Background and Objectives: The provision of emergency care is globally recognized as among the most difficult and challenging elements of any healthcare system. Hamad Medical Corporation (HMC) was facing increasing pressure to introduce initiatives to significantly ease problems with congestion at Hamad General Hospital's (HGH) Emergency Department (ED). This ED is one of the busiest in the world, with an average daily census of 1,500 patients. Due to the large number of patients, fragmented design and inappropriate placement and distribution of resources, all previous attempts at decongesting the ED and improving patient flow were unsuccessful. HGH leaders knew from internal data that the large volume of the male low-acuity patients represented approximately 70% of total ED patients, and were the main reason for congestion and crowding. Therefore, targeting this group would bring about the most significant impact. Methods: Data were studied in order to predict the number of patients who would fit the low-acuity criteria. This study confirmed that up to 70% of all ED patients fell within the low-acuity criteria. Lean process mapping was conducted to determine the current state of patient flow, processes, and practices in the male low-acuity areas of the ED. The impact of the existing fragmented facility design was also studied. Detailed analysis of a patient's journey from arrival to disposition was undertaken. Results: The process mapping confirmed many unacceptable variations when managing low-acuity cases in the ED and it was evident new design and processes were required. A 'See and Treat' service was opened on 7 March 2010 resulting in: reduction in door-to-door transit time, reduction in adverse events and complaints, improvements in maintaining patients' privacy and confidentiality, more appropriate resource utilization, routine referring orthopedic team, better pathway for x-ray, pharmacy and cashier, and new documentation to support efficiency. Conclusions: We believe that the remarkable success of the 'See and Treat' service in such a challenging and unique department as ours is a clear evidence that it should be acknowledged as a benchmark for best practice for the provision of efficient and safe patient care in an emergency department, particularly when managing high-volume, low-acuity presentations.

Background and Objectives: There is an escalating interest among patients and consumers in the use of complementary and alternative medicines (CAM), specifically natural health products, for a variety of illnesses. The public interest in CAM makes it important to explore the attitudes and beliefs of pharmacists involved in selling and dispensing these products. Our objectives were to explore the attitudes of community pharmacists towards CAM and to gauge their opinions about the challenges faced when dispensing CAM during their daily practice. Methods: A qualitative exploratory study was conducted in Doha, Qatar. The Study utilized focus group meetings and a purposive sample of community pharmacists whose pharmacies sell CAM. Recruiting for focus group meetings continued until a point of saturation was reached. The discussions and responses to questions were audio-taped and transcribed verbatim. All recordings were analyzed for recurring themes and subsequently coded and categorized. Results: Most pharmacists felt they were not equipped with sufficient information to competently recommend CAM to their clients and all have no access to information resources to update their knowledge. Pharmacists who graduated from the Indian subcontinent shared strong belief in traditional Indian remedies which shaped their practice in respect to CAM. Pharmacists have doubts about the safety of CAM and felt their undergraduate pharmacy courses did not prepare them to adequately assist their patients. Conclusion: Pharmacists were not confident in dispensing or recommending CAM to their patients. In view of the escalating interest in CAM, and in order for pharmacists to support patient autonomy in selecting health care interventions, colleges of pharmacy should make radical changes in those undergraduate courses that teach subjects related to CAM.

Background and Objectives: Neonatal mortality, a component of United Nations Millennium Development Goal 4 (MDG-4) (two thirds reduction in childhood mortality by 2015), has been a focus of all global health improvement strategies and plans of action since 1990. Our study aims to prospectively ascertain Qatar's neonatal mortality rate (NMR) during 2011, analyze trends between 1975 and 2011, and compare with recent data from high income countries. Methods: A PEARL study (perinatal neonatal outcomes research study in the Arabian Gulf), a joint collaborative research project between Hamad Medical Corporation (HMC), Qatar and University of Gloucestershire, United Kingdom, is Qatar's prospective national perinatal epidemiologic study funded by Qatar National Research Fund. The study quantifies maternal, neonatal and perinatal mortality, morbidities and their correlates by establishing a national neonatal perinatal registry for Qatar called Q-Peri-Reg. Data on live births and neonatal mortality was collected from all public and private maternity facilities in Qatar during 2011 and compared with historical neonatal mortality data (1975-2011) ascertained from the database of maternity and neonatal units of the Women's Hospital and annual reports of HMC. Inter-country comparisons were made using World Health statistics 2011 and the European perinatal health report 2008. Results: Total live births during the study period were 20,583 and neonatal deaths 102. NMR was 4.9, early neonatal mortality rate (ENMR) 2.7, late neonatal mortality rate (LNMR) 2.2 and corrected neonatal mortality rate (cNMR) 3.26. Between 1975 and 2011, relative risk of NMR decreased by 87% (RR 0.13, 95% CI 0.10-0.18, p <0.001), ENMR by 91% (RR 0.09, 95% CI 0.06-0.12, p <0.001) and LNMR by 58% (RR 0.42, 95% CI 0.23-0.74, p= 0.002) though the population increased by 10 fold and number of deliveries by 7.2 folds. The comparable NMR from selected high income countries are between 3 and 5. Conclusion: Qatar has achieved its target MDG-4 by 2011. The improvement has been more marked in ENMR than LNMR. The current NMR, ENMR, LNMR and cNMR are comparable with selected high income counties. Further in-depth analysis of correlates and determinants of neonatal survival in Qatar may form the basis of a strategic global neonatal mortality improvement plan.