Qatar Foundation Annual Research Forum Volume 2013 Issue 1

Background: Developing effective public health policies and strategies for interventions necessitate an assessment of the structure, dynamics, disease rates and causes of death in a population. Lately, Qatar has undertaken development resurgence in health and economy that resulted in improving the standard of health services leading to enhanced life expectancy as was evident in the entire Qatari population (i.e., Qatari nationals and non-Qatari residents). No study has attempted to examine the influence of improving the health services on the homogenous, stable population of Qatari nationals. Objective: The present study examines the population structure and dynamics and the related changes in the cause-specific mortality rates and disease prevalence in the Qatari nationals. Methods: This is a retrospective, analytic descriptive analysis covering a period of 5 years (2007-2011) and utilizes a range of data sources from the State of Qatar including the population structure, disease-related mortality rates, and the prevalence of a range of chronic and infectious diseases. Factors reflecting population dynamics such as crude death (CDR), crude birth (CBR), total fertility (TFR) and infant mortality (IMR) rates were also calculated. Results: The Qatari nationals is an expansive population with an annual growth rate of ~4% and a stable M:F ratio. The CDR declined by 15% within the study period whereas the CBR was almost stable. The total disease-specific death rate, however, was decreased in the Qatari nationals by 23% due to the decline in mortality rates attributed to diseases of the blood and immune system (43%), nervous system (44%) and cardiovascular system (41%). There was a high prevalence of a range of chronic diseases whereas very low frequencies of the infectious diseases within the study population. Conclusion: Public health strategies, approaches and programs, developed to reduce diseases burden and the related death, should be tailored to target the population of Qatari nationals since this population exhibits characteristics that vary from the entire Qatari population.

Background: The incidence of Colorectal Cancer (CRC) peaks in the sixth and seventh decade of life and its precursor lesions a decade earlier in average risk population. American College of physicians (ACP) recent guidelines suggests CRC screening at 50 years of age and older in average risk persons to detect and treat colorectal cancer precursor lesions and early cancers. Objective: To delineate the incidence of Colorectal Cancer (CRC) and Cancer Precursor Lesions (CPL) in the 30 - 49 years age group in symptomatic and asymptomatic average risk population of Doha, Qatar. Method: Lower gastrointestinal endoscopies are routinely done in Qatar for diagnosis and treatment for patients presenting with lower abdominal pain, bleeding or worsening constipation. A retrospective collection of data was done to know the incidence of CRC and CPL among all the patients reporting to our hospital with above mentioned symptoms. Based on the results of this data, a cut off age was calculated with highest sensitivity and specificity for detection of CPL. A CRC screening program was then initiated among asymptomatic subjects with positive immunological fecal occult blood (iFOBT) and age > 40 years were invited for screening colonoscopy. Incidence of CPL (colorectal adenomas) and CRC was calculated prospectively in the average risk asymptomatic population among various age groups. Data regarding the incidence of CRC and CPL among symptomatic and asymptomatic (screened) population was compared. Results: A total of 1489 lower gastrointestinal endoscopies were done in symptomatic patients over a one year period. The mean age was 47.5 years, 935 were males with 71.3 % being expatriates. Overall, among the symptomatic people, CPL were detected in 14.5 % (n= 216) and CRC in 5.6 % (n= 84).Of these, CPL and CRC was detected in 22.6 % (n= 49) and 34 % (n=29) respectively in the age group of 30-49 years. Among the asymptomatic 1242 people who participated in the CRC screening keeping a cut-off age of > 40 years, 57 people (4.6%) were found to be positive for occult blood in stool. Of them, seven and five patients were detected to have CPL and CRC respectively between the age group of 40-74 years. In the 30-49 years age group, CPL was detected in 14.3 % (n=1) but without any CRC. Table 1. Conclusion: One-third of cancers (34%) and one-fifth of cancer precursor lesions (22 %) are detected in the 30-49 years age group in symptomatic patients in Qatar. Among the young (fourth decade of life) asymptomatic subjects, the incidence of cancer precursor lesion remains similar to symptomatic patients but without any obvious cancer. Hence, it is recommended that young symptomatic patients should undergo lower endoscopy early to detect cancer and cancer precursors. Larger studies are required in the asymptomatic subjects of 40-49 years age group to estimate the incidence of pre-cancerous lesions that might benefit from CRC screening.

In recent years a specialist interest has developed worldwide in Advanced Wound Management for difficult to heal chronic wounds. This is timely given the increasing number of elderly in the population and the growing burden of diabetes, obesity and cardiovascular disease that all contribute to an increase in hard to heal wounds. Further progress in Advanced Wound Management will require an improvement in personalised medicine for the patient and in particular an improvement in the availability of diagnostic tests and parameters that fulfil clinical need in wound management decisions. At the current time in wound care there is little available in near patient testing for clinical diagnostics. This research project focuses on a number of metrics for wound condition and wound healing: wound moisture, wound fluid pH, and wound matrix metalloproteinases (MMP) enzyme activity. To observe these important markers a state of the art sensor for wound moisture monitor is being deployed in clinical studies and new sensors are currently in development for both pH and MMP-9 enzyme level. Moisture levels in wounds can determine how well a wound heals and in addition it is possible to make decisions on the need for dressing changes based upon moisture readings taken from inside the dressing. The pH of a wound can affect many different phases of the healing process such as oxygen levels, cell proliferation, protease enzyme activity and bacterial growth. If the pH level of a wound can be effectively monitored then it can act as a biological marker to aid in diagnostics and in establishing the optimum conditions for healing. The pH electrode has not been successfully adapted into smaller and alternate packaging because the membrane that forms the selective part of the electrode, being made of silicon glass, is fragile, thus limiting manufacture, sterilisation and practical application. A disposable sensor has been produced through a screen printing method with an ion-selective membrane. The sensor is able to detect the pH in an operational range in the pH 3.5-10 with as little 10µL of fluid. MMPs are involved in every phase of wound healing. If the balance of the MMPs is upset within a wound it can upset the cellular processes preventing healing and eventually causing further damage to the wound. In chronic wounds the amount of MMP-9 activity has been found to be 30 times more than in acute wounds. By measuring the MMP-9 level of a wound the clinician will be able to choose treatment appropriately to return the MMP level to optimum healing conditions. The project has developed an assay for measuring MMP-9 at physiologically relevant levels between 0.01-100ng/ml. These sensors will enable the wound healing markers of moisture, pH and MMP enzyme activity to be studied and profiled in Hamad Medical Corporation which will further the understanding of these markers and their relationship in the complex healing process involved in chronic wound healing.

Background and Objectives-Salmonella enterica is one of the most commonly reported causes of bacterial foodborne illness around the world. Many factors, including food of animal sources, play a role in the predominance of certain serovars. The occurrence of S. enterica serovars varies between different geographical regions and data on their occurrence in Qatar is lacking. Knowledge on the occurrence of zoonotic serovars and associated factors will help to design cost-effective risk mitigation strategies. This risk of salmonellosis has been exacerbated by the ease of travel around the world, increase in world trade of food and animal items, and continued migration of people. Qatar is one of the countries where the factors that exacerbate the risk of foodborne diseases intersect. We carried out a combination of epidemiologic and molecular studies to investigate the distribution of S. enterica serovars in this highly diverse population, and to identify the factors that play a role in the predominance of a particular serovar. Methods-We carried out a repeat cross-sectional study in which human and non-human samples were collected and Salmonella spp. were detected using a combination of bacterial enrichment and real-time PCR. Salmonella isolates were analysed using the Multi-locus sequence typing (MLST) scheme and assigned accordingly by their eBURST groups (eBGs). We used the minimal spanning tree (MST) analysis to investigate the relationship among the isolates from different sources. Data on putative risk factors were collected and analysed for significance of association with particular serovars. Results-We identified 27 different sequence types (STs) and the most common were ST11 (29.5%) and ST19 (11.5%). Among the 27 STs, seven were novel (ST1695, ST1696, ST1697, ST1698, ST1699, ST1702, and ST1703). The STs related to serovar Enteritidis were ST-11, ST1695, and ST-1702; to Typhimurium were ST-15, ST-19, and ST-568; and to Newport were ST-31, ST-808, and ST-1698. Three of them were revealed to be common serovars in this study. In the MST analysis, three major clusters were presented in the overall population: Enteritidis, Newport and Typhimurium. Furthermore, it also revealed the possibility of transmission of strains between human and animal sources according to the lineages of STs. It was more likely to detect serovar Enteritidis in Qataris and serovar Typhimurium in non-Qataris in this study population. Conclusions—A diverse set of serovars were identified among the samples which could be due to the large scale of emigration and importation of animal feed and products in Qatar. Overall, our data also reveals the possibility of transmission of Salmonella isolates between human and animals; however, a detailed analysis of larger sample over a longer period of time using whole genome sequencing (WGS) could help to shed more light on the dynamics of transmission between these populations.

Background and objectives-Foodborne illness has been determined to be one of the major limitations to the advancement of world health and with the ease of travel around the world and the increase in trade of food and animal products, the risk has been exacerbated in recent years. It has been proclaimed as one of the high priority issues in the Qatar National Food Security Master Plan. Different estimates of burden of disease consistently indicate a high cost per episode, irrespective of the country where the study is conducted. The mechanism by which foodborne pathogens cause disease is complex and the cytolethal distending toxin (CDT) has been identified as one of the virulence factors that contributes to gastroenteritis. The CDT is a trimeric subunit toxin produced by gram-negative bacteria that causes cell-cycle arrest and causes affected cells to die by apoptosis. In an effort to understand the mechanisms by which foodborne pathogens put humans at risk of chronic gastroenteritis sequelae, this study investigated the occurrence of the CDT among Salmonella spp., Escherichia coli serogroups and Campylobacter spp. isolates recovered from animals and humans in Qatar. Methods—Samples collected from animals and humans were screened for the presence of these three foodborne pathogens using a combination of bacterial enrichment and molecular detection. Positive samples were further examined for the presence of the CDT gene and its three subunits (cdtA, cdtB, cdtC) using a polymerase chain reaction (PCR) approach. Results—To date the cdtB gene was detected in C. jejuni and C. coli isolates from animals at a rate of 70 and 89%, respectively. The cdtC gene was detected in 72% of the C. jejuni animal samples examined to date. Only cdtB was detected in Salmonella spp. and E. coli spp. isolates from animals and at a much lower rate. Both cdtB and cdtC were detected at a higher rate among C. jejuni and C. coli recovered from human cases enrolled in this study (Figure 1). Conclusions—The high prevalence of the CDT genes among Campylobacter isolates in both animal samples and human clinical cases suggests a possible critical role for the toxin in the pathogenesis of the diseases caused by these pathogens. By virtue of its toxicity, CDT has been incriminated in the risk of chronic gastroenteritis sequelae, including Inflammatory Bowel Disease and is likely to play role in the risk of this disease among human population in Qatar.

There are obvious and well known links between air quality and acute respiratory illnesses that are common in Qatar and other Middle Eastern countries. For example, recent studies have documented a number of respiratory problems associated with inhalation of dust during dry, windy periods. In Qatar, exposure to dust and sand are anecdotally associated with a variety of respiratory issues including asthma and chronic obstructive pulmonary disease (COPD). These illnesses may be brought about by physical damage caused by the particles themselves, or by microorganisms that can be associated with these particles. In this study we will examine the relationship between different climatic variables, daily airborne particulate matter, and hospital admissions for respiratory problems over an eight month period to establish possible relationships. The results of the study will shed light on the importance of weather phenomena, particularly windy conditions, in impacting respiratory health in Qatar. These data are particularly important as respiratory problems are expected to increase as climate change results in hotter, drier conditions over the next few decades.

Abstract (342 words) Background: The scale and nature of hepatitis C virus (HCV) disease burden in Qatar is poorly known. In addition to establishing the level of infection among the Qatari population, characterizing HCV disease burden is of particular relevance as Qatar has a large expatriate population some of whom are from countries with substantial HCV prevalence. Objective: To investigate the epidemiology of HCV in Qatar among Qataris and expatriate resident populations. Methods: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Sources of data included PubMed and Embase databases. Our analysis included all primary studies reporting HCV prevalence or incidence measures in Qatar. Extracted measures were then classified and analyzed on the basis of the study population's risk of acquiring HCV. Meta-analyses were conducted incorporating inverse variance weighting and using a random-effects model to pool summary estimates of HCV prevalence, among general population groups, for Qataris and the population as a whole. Results: We identified seven studies providing a total of 23 measures on HCV prevalence and none on incidence in Qatar. HCV prevalence in the general population was 0.51% (95% confidence interval (CI): 0.43-0.59) among Qataris, and 1.01% (95% CI: 0.43-1.82) overall. Among blood donors the prevalence ranged from 0.3-11.2% depending on country of origin. The highest prevalence was reported among Egyptian migrants followed, though by a large margin, by Pakistani migrants. Among high risk populations, HCV prevalence was as high as 44.6% in hemodialysis patients, 25.8% among cirrhosis patients, and 9.0% among lichen planus patients. Conclusions: National-level HCV prevalence in Qatar is comparable to that in developed countries, but higher prevalence is found in specific expatriate populations reflecting the higher prevalence in the countries of origin. The high prevalence found among high risk groups possibly dates back to exposures that occurred prior to the enforcement of stringent infection control and blood screening protocols, implemented in the 1990s after the virus discovery. Since HCV prevalence is rather low, HCV prevention policy in Qatar should focus mainly on prevention and infection control in clinical settings.

Dilated Cardiomyopathy (DCM) is a leading cause for heart failure characterized by an enlarged ventricular cavity causing systolic dysfunction. Although a multifactorial disease, DCM has been attributed to gene mutations in approximately 30-50% of cases. However, the full spectrum of the genetic basis of DCM remains elusive. QCRC-IGC is a Doha-centered intercontinental consortium comprising teams from Egypt, Greece, UK, Italy and the USA. It aims at discovering novel gene variants implicated in DCM pathogenesis and/or progression, through the establishment of a multinational DCM patient cohort and the genetic investigation of over 170 genes (including all DCM genes) using the cutting-edge technology of Next Generation Sequencing (NGS). Herein we present the genetic screening of sixteen DCM patients (5 sporadic and 11 familial), as confirmed by echocardiography and/or MRI, who did not have a history of alcoholism or coronary angiography findings. Over 1,600 variants were detected in each patient, the vast majority of which represent well documented benign polymorphisms. Forty variants had never been reported before, involving the genes: TTN, SYNE1, MYH6, ALMS1, SDHA, MYPN, LAMA2, TPM1, PLEC, FOXD4, ILK, SGCB and DSP. TTN mutations are being detected in 27% of DCM cases. Of particular interest is the polymorphism observed in the gene DSP, as it was detected in two affected sisters of the same family, it represents the only common potentially pathogenic variant shared between them, and it is bioinformatically predicted to lead to a dysfunctional protein product. Importantly, other mutations in DSP have been previously associated with DCM as well as ARVC. Significant findings of immediate research and ultimately diagnostic/prognostic value are beginning to emerge. Additionally, the discovery of novel pathogenic mutations would unveil promising new therapeutic targets. QCRC is currently intensifying the patient recruitment process at the clinical level, while focusing on the molecular characterization of the emerging novel variants using in silico modeling, induced pluripotent stem cells, and systems biology approaches.

Abstract- Developing visual prosthesis in human cortex or on retina has gained some importance over years. However, visual prosthesis in thalamic region targeting lateral geniculate nucleus (LGN) has few advantages though. This paper proposes a simulation model for deep brain visual prosthesis that will harness the capacity of the residual central visual neurons. This prosthesis creates percepts, substituting an engineered prosthetic for the image capture and early visual processing properties of the LGN neurons that we plan to drive artificially. Introduction- Glaucoma is an incurable neurodegenerative disorder leading to permanent blindness. Glaucoma accounts for blindness in 4-5 million of the world's people and is unusually prevalent in Eastern Arabia. In Qatar, glaucoma is said to account for 40% of its cases of blindness and 16% of people above age 40 are affected by this disease. Restoration of visual function in glaucoma by stem cell therapy or genetic engineering could provide a quite good solution, but the likelihood of these approaches providing a cure for glaucoma in the near term is tenuous. A neuroprosthetic approach offers the most likely short-term treatment for glaucoma-induced blindness. This paper describes early progress made towards designing a visual prosthesis to treat blindness through glaucoma. In glaucoma, there is evidence that the LGN undergoes degenerative changes in human patients [1]. Obviously, LGN degeneration during glaucoma needs to be factored into the design of the electrode array. Design and Concept- The proposed design of the visual prosthetic requires many components (Fig 1). The electrodes are positioned in the dorsal layers of the LGN and all other components located outside the body. Images are captured and adjusted for position of gaze and processed by spatiotemporal filters to provide signals that can be used to drive LGN neurons similar to their natural drive. These signals drive the electrode array with a pattern of stimulation pulses. Electrical stimulation circuitry provides charge-balanced current pulses to the electrodes to activate LGN neurons. Results- An array of electrodes distributed across a semi-elliptical shaped flat surface that interfaces with the top three LGN layers (layers 6-4) is designed. The flat semi-elliptical shaped head, resembling the tip of a knife, facilitates easy penetration through the soft brain tissue. To match LGN dimensions, the head would be 2.5 mm wide, 2 mm deep and 50 µm thick. Fig 2 shows the proposed design with 184 hemispherical shape electrodes placed on either side of the lead with diameters of 50 µm and center to center spacing of 200 µm. The hemispherical shape of electrodes avoids concentration of current density at one place since it does not have any corners or edges. Thus these electrodes deliver uniform current density around the electrode minimizing the electrode and tissue damage. The electrodes are placed in a triangular array to maximize packing density and maintain equal distance between neighboring electrodes. Reference- [1] Gupta, N. et al., 2009. Atrophy of the lateral geniculate nucleus in human glaucoma detected by magnetic resonance imaging. The British journal of ophthalmology, 93(1), pp.56-60.

Design of a new Wavelet-based preprocessing stage for improved time-frequency detection of fetal movements Dr. Taoufik Ben Jabeur and Pr. Boualem Boashash Department of Electrical Engineering, Qatar University Background: Improving Newborn Health Outcomes can be achieved by monitoring Fetal Movement (FetMov) activity which relates directly to the fetus well-being. Several methods exist to record these Fetal movement (FetMov) signals including active (Ultrasounds) and passive ways (accelerometer). Ultrasound is an accurate measurement but expensive and intrusive; for these reasons, capturing FetMov through accelerometer sensors is a preferred option as it is low cost and nonintrusive. In this approach, different sensors are placed on the abdomen of the pregnant woman. Each sensor produces a FetMov signal. The recorded FetMov signals have been shown to be noisy and non-stationary signals containing several artifacts. Thus, a pre-processing stage is required to reduce the noise and eliminate the artifacts. Objectives: This work aims at designing a new pre-processing stage for improving FetMov detection by applying Wavelet de-noising algorithm followed by a threshold given by Kurtosis parameter. Methods: The new method is based on a Wavelet de-noising algorithm followed by a high pass filter to reduce some artifacts. A threshold given by Kurtosis parameter is used in the elimination of the artifacts. Results and conclusion: Simulation results show that the proposed pre-processing stage allows to reduce the noise and to eliminate more than 70% of the artifacts. Few artifacts are still present in the FetMov signals. As the FetMov signal is non-stationary, we use a Time Frequency Matched filter detector (TFMF) based on QTFDs to detect FetMov from these artifacts. The proposed preprocessing stage combined with TFMF detector improves significantly the performance of the detection of the FetMov signal leading to possible improvements in health outcomes for the fetus. Keywords: Fetal movement; Wavelet; Time frequency Matched Filter; Quadratic Time Frequency Distribution.