bluuebunny/crossref_metadata_2025 huggingface dataset:
Think small: The zebrafish as a novel disease model in QCRC
Authors: Yacoub Magdi , Brand Thomas , Schlueter Jan
Published: October 2012

Animal models are essential to understand the molecular and cellular basis of human pathologies. The zebrafish has gained significant attention as a novel model system and has several advantages over rodent models, including: (1) genetic and physiological similarity to humans, (2) a high fertility rate, (3) external fertilization, (4) ease of genetic manipulation, (5) enlarging library of heart-specific reporter genes, (6) ability to survive with a dysfunctional heart, (7) transparency enabling powerful imaging modalities. The zebrafish heart has only two chambers but beats with a heart rate comparable to humans. Several genetic models have been engineered, which successfully model cardiac conditions. Random integration of reporter genes by transposon-mediated transgenesis generated a large number of zebrafish lines, specifically labeling different cardiac cell types and tissues. These include marker genes that label the myocardium, epicardium, endocardium, the conduction system, and atrioventricular and aortic valves (see Figure). Such reporter lines are useful to monitor specific cardiac cell populations and to study their role in disease processes. Similar efforts have recently been employed to identify the cell population responsible for cardiac regeneration. Gene mutations identified in humans causing cardiomyopathies have been introduced in zebrafish and successfully modeled the disease process in this species. Moreover, chemical genetic approaches have been successfully employed to identify small molecules, which are able to reverse pathological conditions such as hypertrophic cardiomyopathy. These examples demonstrate the power and versatility of this model organism, which will pave the way for novel therapeutic opportunities to treat cardiovascular disease. In the Qatar Cardiovascular Research Center we plan to utilize the zebrafish model to study the genetic basis of aortic valve disease, hypertrophic cardiomyopathy, and heart failure. A zebrafish lab will be established in Doha as part of the network in order to develop local expertise and to contribute to the overall research efforts.
Late stimulation of myocardial recovery, following insertion of a continuous flow LVAD
Authors: Yacoub Magdi , Helmy Sherif , Al Hashemi Mohamed , Terracciano Cesare , Ibrahim Michael , Bonow Robert , Badr Amr
Published: October 2012

The use of mechanical assist devices for the treatment of advanced heart failure has increased dramatically in recent years.

Significant recovery of myocardial function following insertion of left ventricular assisted device (LVAD) occurs in a small percentage of patients due to unloading alone. Several strategies for enhancing the degree of recovery using combination therapy have been introduced. Most of these strategies depend on early use of pharmacologic agents to stimulate reverse remodelling followed by inducing physiologic hypertrophy.

We here report the use of the funny current inhibitor ivabradine late after insertion of Heart Mate II in Doha. This was performed following experimental studies in a small animal model which showed the drug induces reverse re-modelling when used in combination with unloading by abdominal heart transplantation. Sequential studies were performed using non-invasive myocardial function and exercise testing after reducing the pump speed to 6,000 RPM, which in effect stops forward flow through the pump. This was performed under full heparinisation. These tests have shown progressive recovery of function following the institution of the combination therapy.

Further studies using LVAD's as a platform for recovery are being investigated at QCRC. These studies include formal exercise program and gene and cell therapy. In addition, an extensive basic science program to investigate the mechanisms of recovery is in progress.
Investigation of genes that are related to colorectal cancer and liver metastasis
Authors: Adawn Hassan , Georges Rania , Berger Martin R.
Published: October 2012

Progression of colorectal cancer (CRC) culminates in liver metastasis. To identify genes that are involved in the metastatic phenotype, cDNA microarrays were used to analyze mRNA expression profiles of CC531 rat colon adenocarcinoma cells for changes related to their homing into the liver. Briefly, CC531 cells were intraportally implanted into the liver of Wag-Rij rats and re-isolated after 3, 6, 9, 14 and 21 days.

Altogether 2919 genes from ca. 25000 genes were deregulated as a response to metastasis formation into the liver. Candidates from promising gene families were chosen for further analysis using different in vitro models and human CRC samples. These gene families included the claudins and the insulin-like growth factor binding proteins (IGFBPs).
For claudins, it was shown that the initial phase of rat CRC cell homing into the liver involves a transient down-regulation of several claudins. Also it was shown that siRNA silencing of Cldn1 and Cldn4 increased migration and reduced colony formation, with these phenotypes being consistent with metastatic homing.

Correspondingly, human CRC samples showed increased Cldn1 and Cldn4 expression in UICC stages l-lll, and significantly reduced expression in stage IV and in liver metastasis. Additionally, the IHC analysis revealed that the expression of Cldn1, Cldn4 and Cldn3 in liver metastasis specimens was lower than in the corresponding primary carcinomas. Taken together, metastasizing cells require a transient reduction in claudin expression for liberation from the primary tumor and then initialization metastatic growth in the liver.
For IGFBPs it was shown that deregulation of IGFBP3 and IGFBP7 is related to the metastatic behavior of CRC cells. In CRC patients, a significant correlation between the expression levels of these genes was noticed but no relation to overall survival was registered. Further, the patients' age was inversely correlated with the expression of IGFBP3. Silencing of IGFBP3 and/or IGFBP7 in human and rat colorectal cancer cell lines reduced proliferation, colony formation, and for IGFBP3, also migration. These results indicate that IGFBP3 and 7 cannot be simply assigned to the group of tumor suppressors, but have additional properties, which become evident only in the context of cancer progression and metastasis formation.
Spatio-temporal characterization of the blood flow in the aortic root
Authors: Yacoub Magdi , Torii Ryo
Published: October 2012

Background:
The flow profile in the aortic root constitutes a major determinant of coronary and systemic blood flow, depending on the size, shape and dynamism of the aortic root. The aims of this study are to evaluate patterns of flow in the aortic root in health, disease and following different root replacement procedures.

Methods:
A total of 54 subjects underwent phase-contrast cardiovascular magnetic resonance (PC-CMR). Of those, 29 patients with well functioning aortic valve substitutes had undergone aortic root replacement > 10 years earlier. They were divided into 3 groups: autografts (n = 13, 47±9 years), stentless porcine xenografts (n = 10, 77±8 years) and homografts (n = 6, 71±11 years). The remaining patients had bicuspid aortic valve (BAV, n = 4, 32±17 years) and obstructive hypertrophic cardiomyopathy (HCM, n = 6, 43±9 years). A cohort of 15 healthy volunteers (31±5 years) served as controls to determine normal spatio-temopral flow patterns.

Results:
The aortic root flow profiles showed differential patterns: (1) BAV patients had a high velocity jet through the narrow valve orifice; (2) HCM patients had eccentric flow patterns due to the obstruction in the left ventricular outflow tract; (3) flow through the autograft valve was triangular in shape reflecting ideal orifice shape of a triliaflet valve, similar to normal controls and (4) flow patterns through the xenografts and homografts are more disrupted than autografts. The maximum velocities for BAV, HCM, autograft, xenograft, homograft and control groups, respectively, were: 2.6±1.8 m/s, 1.6±0.2 m/s, 1.2±0.2 m/s, 2.1±0.9 m/s, 1.7±0.4 m/s, 1.0±0.3 m/s.

Conclusions:
Flow profiles in the aortic root vary markedly according to the type of disease and root substitute. Among the tissue root substitute options, the Ross procedure best reproduces normal flow dynamics.
Examining secular trends in the utilization of warfarin among Middle Eastern Arab and South Asian patients hospitalized with atrial fibrillation: 20-year experience from Qatar (1991-2010)
Authors: Salam Amar M , AlBinali Hajar A , Al-Mulla Abdul Wahid , Singh Rajvir , Al Suwaidi Jassim
Published: October 2012

Objectives:
There is paucity of data relevant to anticoagulation rates and trends of treatment in patients with atrial fibrillation (AF) in developing countries and whether there are ethnic differences in the utilization of warfarin as some reports have suggested. The aim of this study is to evaluate trends of utilization of warfarin in 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. Rate and trends of warfarin use was examined in relation to ethnicity over the years of the study.

Results:
During the 20 year period; 2857 Arabs and 548 Asians were hospitalized for AF. The mean age of Arabs was 58 years and of Asians 49 years. Overall, 31.8% of Arabs and 39.4% of Asians received warfarin at hospital discharge (p= 0.001). The overall use of warfarin was significantly trending higher from 17 % in the earlier years of the study to 44.1% in the latter years but no differences were found between Arabs and Asians throughout the study period except at the latter years of the study when it was significantly higher in Asians (53% Asians vs. 41.7% Arabs; p= 0.009).

Conclusions:
Although the trend is significantly increasing over time, warfarin remains underutilized in patients hospitalized with AF irrespective of ethnicity. There is an urgent need for prospective studies to investigate warfarin contraindications, relative warfarin efficacy and bleeding risks in our region to help guide healthcare providers prescribing warfarin and consequently reduce the risk of AF-related disabling strokes.
An echocardiographic screening of school children for rheumatic heart disease in Aswan, Egypt
Authors: Yacoub Magdi , Kotit Susie
Published: October 2012

Introduction:
The global burden of rheumatic heart disease continues to be extremely high, with the main brunt being borne by developing countries. However, the prevalence and disease characteristics vary widely in different populations. Egypt hosts 80 million individuals and is known to be endemic for rheumatic heart disease.

Methods:
Cross sectional screening of a cohort of randomly selected 3062 school children between the ages of 5 and 15 years in Aswan, a "neglected "part of Egypt. The schools were stratified by area and age group and randomly selected using computer generated random-number. After ethical approval, the children underwent detailed physical and transthoracic echocardiographic examination. A set of rigid criteria including structural and functional changes in left sided valves, were used to determine the presence, distribution and severity of rheumatic affection. The disease was categorized into definite and possible.

Findings:
The mean age of the children examined was 10 (2*6) years with slight male preponderance (58.7%) which was representative of the whole school population. None of the children were on penicillin prophylaxis or were known to have cardiac disease. Definite and probable rheumatic valve affection was present in 23 and 13*4 per thousand respectively. Mitral valve affection (mainly regurgitation )was present in 96%, aortic regurgitation in 2.9% and combination of both in 1.4%. Left ventricular function was normal in all patients. Auscultation revealed a murmur in 7.1% of children with echocardiographic evidence of rheumatic heart disease showing a 14 fold increased detection rate by echocardiography.

Interpretation:
Asymptomatic rheumatic heart disease is common in school children in Aswan. The disease affects predominantly the mitral valve producing regurgitation in the majority, These findings are important for instituting early secondary prevention and stimulating future development of specific biomarkers and vaccine development.
Characterization of wall biomechanics of the pulmonary autograft after the Ross procedure
Authors: Yacoub Magdi , Torii Ryo , Ibrahim Michael
Published: October 2012

Background:
There is continuing concern about the risk of long-term autograft dilatation and rupture following the Ross procedure. The aim of this study is to characterize the neo-aortic valve in terms of morphology and wall distensibility.

Methods:
Among 108 Ross patients undergoing yearly echocardiographic assessment in our unit, 17 (16%) had aortic root diameters of >45mm (DG) 14 ± 1 years after operation. In an attempt to characterize the autograft morphology and dynamics, 11 patients (age 47 ± 10) with dilated autografts underwent cardiac multi-slice computed tomography (CT). Dimensions and distensibility of the aortic root were derived from the cine-CT images. Morphological observation was also made with rapid prototyping models based on the multi-slice CT. The patients were compared with 11 age-matched normal controls (C, age 47 ± 9).

Results:
Sinus diameters (Ds) were increased in DG compared to C (50 ± 3 mm vs 31 ± 4 mm, p < 0.01). The non-coronary sinus of the autograft tended to enlarge to a greater extent than other two sinuses. Aortic diameters (Da) were also increased in DG (35 ± 6 mm vs 28 ± 3 mm, p < 0.01). DG patients had similar cyclic strain (7.2 ± 3.8% vs 8.3 ± 3.6%, p = 0.13) and distensibility (25 ± 14 vs 34 ± 14 MPa-1, p = 0.20).

Conclusions:
These data support the notion that the autograft root has similar physical properties to the normal aortic root despite significant dilation. This may have implications for both the selection of aortic root substitutes and the clinical management of Ross patients presenting with dilated roots.
Designer scaffolds for tissue engineering heart valves
Authors: Yacoub Magdi , Krishnamoorthy Navaneeth , Sohier Jerome
Published: October 2012

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.
What are the changes in oxidative stress and DNA in response to cycling in a thermal challenging environment?
Authors: Knez Wade
Published: October 2012

Background
A hot environment is associated with an increase in core temperature and dehydration. However, there are minimal data investigating the time course of changes in oxidative stress and DNA in response to cycling in a hot environment. Additionally, it is not known whether there is a critical point in core temperature for the production of oxidative stress or DNA modification. Subsequently, this research investigated the time course of changes in markers of oxidative stress and DNA modification during and after exercise in a hot environment.

Methods
Eight cyclists (age=30.9±2.2yrs; height=177.9±4.1cm; mass=74.5±4.5kg) completed a cycling VO2max in hot conditions (35°C, 70%RH) to determine 60% of peak power output (PPO). One week later they returned and cycled at this intensity until they reached a core temperature of 38.5°C. Blood was sampled before, during, and after (0, 10, 25, 35, post 10 and post 20 mins) exercise to determine changes in oxidative stress and DNA. Statistical analysis was completed using linear mixed models with a level of significance set at p≤0.05.

Results
Cycling at 60% of PPO until core temperature reached 38.5°C resulted in a significant increase in oxidative stress over the exercise bout. Data showed that oxidative stress increased during exercise period (0-10, 25, 35 min [0 min post]) and decreased from 0-post to post 20 min recovery. After correcting for multiple comparisons, there was a tendency towards significance from 0 mins to the completion of the exercise bout. However, no changes were observed in the modification of DNA during exercise or recovery. No relationship was observed among the changes in blood markers and core temperature.

Conclusion
Research shows that regular exercise protects against exercise-induced changes in oxidative stress and DNA. This research shows that this relationship extends to exercising in a hot environment. Changes in oxidative stress appeared to be more sensitive to exercise duration than core temperature. Furthermore, these data showed that there was no critical core temperature for the development of oxidative stress. However, the current project was limited to a maximum core temperature of 38.5°C. Future research should continue exercise beyond this point to develop a clearer understanding.
Selecting the maximum relevant translated EEG time-frequency features with a minimum redundancy using the mutual information measure for newborn seizure detection and classification
Authors: Boubchir Larbi , Boashash Boualem
Published: October 2012

Background
Analyzing the Electroencephalogram (EEG) is a standard approach for detecting newborn seizure. The manual detection of newborn seizure by visual scanning of EEG recordings is time consuming especially with long recordings. It also requires skilled interpreters, i.e. a neurophysiologist, resulting in possible subjective judgment and error. Hence, the EEG signal parameters extracted and analyzed using computer based digital signal processing techniques are highly useful in diagnostics and more suitable for detecting newborn EEG seizures and other abnormalities.

Objective
This work aims to select the maximum relevant translated EEG time-frequency features with a minimum redundancy to improve the classification accuracy performance of newborn seizure detection and classification systems.

Method
The automatic newborn EEG seizure detection and classification system includes pre-processing of EEG signals, finding their optimal time-frequency distributions (TFDs), extracting features from the TFDs, and finally allocating the T-F features to the relevant class. Based on this classification system, a new approach is proposed to improve their performance, and includes the following stages: Defining T-F features by translating some relevant time features and/or frequency features in the T-F domain; selecting the maximum relevant translated T-F features with a minimum redundancy using the mutual information measure and using the selected relevant features to characterize and classify different newborn EEG seizures.

Results
The experimental results show that the selection of a minimum set of relevant translated EEG T-F features according to a combined minimal-redundancy and maximal-relevance criterion significantly improve the performance of the newborn seizure classification system based on the use of T-F features extracted using both signal and image processing techniques, by up to 4% for 100 real newborn EEG segments. The better results are obtained using the modified-B distribution and the spectrogram distribution with the multi-class SVM classifier. Also, the use of the selected features reduces the computation cost of the classification system.

Conclusion
The improvement obtained is dependent on the choice of relevant translated EEG T-F features. The latter can also be extended and applied to detect other newborn EEG abnormalities.
Reducing cost in sequential testing: A limit of indifference approach
Authors: Ahmed Anwar E
Published: October 2012

In non-inferiority studies, a limit of indifference is used to express a tolerance in results such that the clinician would regard such results as being acceptable, or 'not worse'. We applied this concept to a measure of accuracy, the receiver operating characteristic (ROC) curve, for a sequence of tests. We expressed a limit of indifference for the range of acceptable sensitivity values and examined the associated cost of testing within this range. In doing so, we generated the minimum cost maximum receiver operating characteristic (MCMROC) curve which reflects the reduced sensitivity and cost of testing. We compared the MCMROC and its associated cost curve between a limit of indifference set to 0.99 (a 0.1% reduction in true positive rate, TPR), 0.95 (a 5% reduction in TPR), and 1 (no reduction in TPR). The limit of indifference tended to have less of an effect on the MCMROC curves than on the associated cost curves which were greatly affected. Cost was reduced at high false positive rates (FPRs) at higher limit of indifference (0.99), and at small FPRs as the limit of indifference decreased (0.95). These patterns were also observed as applied to sequential strategies used to diagnose diabetes in the Pima Indians.
Attitudes and practices of community pharmacists about complimentary and alternative medicines (CAM) in the State of Qatar: A qualitative study
Authors: Kheir Nadir , Gad Atwa Hoda , Abu Yousef Safae
Published: October 2012

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.
Qatar achieves its target of neonatal survival required by United Nations Millennium Development Goal 4: A PEARL study analysis
Authors: Rahman Sajjad ur , Al Rifai Hilal , El Ansari Walid , Nimeri Nuha , El Tinay Sarrah , Salameh Khalil , Tohid Hiba , Tahir Mohammad , Bener Abdulbari
Published: October 2012

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.
Using CO2 laser for transmyocardial laser revascularization (TMLR)
Authors: Ali Mohamed , Zaher Amr , Ali Carmen M.
Published: October 2012

Background:
Coronary artery disease remains one of the leading causes of morbidity and mortality in developed countries and is projected to be the leading cause of death in the developing world by 2010. Affecting nearly 12 million people in the USA, it accounts for 50% of all cardiovascular deaths and is the leading cause of congestive heart failure as well as premature permanent disability in workers. About 1.1 million myocardial infarctions and >400,000 new cases of congestive heart failure each year, cardiovascular disease severely impacts men and women as well as various ethnic groups.

Objectives:
The aim of this study is to evaluate the results of transmyocardial laser revascularization (TMLR) in patients with coronary artery disease, in whom percutaneous transluminal coronary angiography (PTCA) or coronary artery bypass grafting (CABG) cannot be done.

Method:
Fifty patients were included in the study:
1) Canadian cardiovascular angina class (CCS) III or IV patients (only 5 patients with CCS class II were included and those patients were the early trial in year 1997 where the recommendations for TMLR was not yet established);
2) Ejection fraction of 30%;
3) Those with evidence of reversible ischemia (based on stress thallium perfusion scanning);
4) Candidates of neither CABG or PTCA (according to the results of coronary angiography).
The laser system used was a heart laser system (PLC medical systems).

Results:
There was a significant improvement in the severity of angina as assessed by Canadian Cardiovascular Society grading after the procedure. Improvement was noticed after 1 month and the improvement was most significant after 3 months and then slightly declined after 6 months but still significant in comparison to the pre-procedural values (P <0.05). Also, there was a significant improvement in the grade of dyspnoea as assessed by the New York Heart Association functional dyspnoea class and the most significant improvement was after 3 months and the degree of improvement decreased but still significantly better than the pre-procedural values (P <0.05).

Conclusion:
TMLR offers consistent amelioration of severe angina in patients having no conventional therapeutic alternative. Surgeons should recognize that the procedure is intended only for the purpose of reducing angina symptoms.
The potential of intra-articular injection of chondrogenic-induced bone marrow stem cells to retard the progression of osteoarthritis in a sheep model
Authors: Alfaqeh Hamoud Hussein , Idrus Ruszymah Bint haji , Yahya Nor Hamdan Mohamad Yahya , Chen Cheng Hui , Aminuddin Saim
Published: October 2012

Background:
Osteoarthritis (OA) is the most common joint disease in middle aged and older people. Despite the multiple modalities of treatment, the outcome is still poor and focuses on temporary measures to alleviate the symptoms.

Objectives:
We want to determine whether or not an intra-articular injection of a single dose of chondrogenic induced bone marrow mesenchymal stem cells (BMSC) can promote cartilage regeneration in surgically induced osteoarthritis in sheep.

Methods:
Sheep BMSCs were isolated and divided into two groups. One group was cultured in chondrogenic media containing 5 ng/ml TGFβ3 + 50 ng/ml IGF-1, and the other group was cultured in basal non-chondrogenic media for the duration of 3 weeks. The procedure for surgically inducing osteoarthritis was performed on the donor sheep six weeks prior to intra-articular injection to the knee joint. The injection is a single dose of BMSCs from either group, suspended in 5 ml Dulbecco's Modified Eagle Medium (DMEM) at density of 2 million cells/ml. The control groups were injected with basic cell free media.

Results:
Six weeks after injection, evidence of articular cartilage regeneration and meniscus repair in osteoarthritic knee joints treated with autologous BMSCs cultured in chondrogenic medium were observed. No evidence of regeneration and meniscus repair was observed for the control group and the group treated with BMSCs cultured in basal medium.

Conclusions:
Intra-articular injection of a single dose of BMSCs in chondrogenic culture could stimulate regeneration of articular cartilage and meniscal tissue.
Use of augmentative and alternative communication as a new system in communication disability
Authors: Ahmad Amal Idres , Omar Azhar Othman
Published: October 2012

Success in life can be directly related to the ability to communicate. Full interpersonal communication substantially enhances an individual's potential for education, employment, and independence. Therefore, it is imperative that the goal of augmentative and alternative communication (ACC) use be the most effective interactive communication possible. For more than three decades now, the field known as augmentative and alternative communication (AAC) has addressed the communication needs of individuals who cannot consistently rely on speech for functional communication.

Changes that result from aphasia are sudden, unexpected, and unwanted. Adjustment is difficult for the person with aphasia. It also presents a great challenge to the family. There may be tension among family members and feelings of frustration and helplessness. The condition may seem hopeless. They may feel neglected and may find it difficult to have a family dependent on it.

The American Speech and Hearing Association defines AAC as an area of clinical practice that attempts to compensate (either temporarily or permanently) for the impairment and disability patterns of individuals with severe expressive communication disorders (i.e., the severely speech-language and writing impaired). AAC incorporates the individual's full communication abilities and may include any existing speech or vocalizations, gestures, manual signs, and aided communication. AAC is truly multimodal, permitting individuals to use every mode possible to communicate. An AAC system is an integrated group of four components used by an individual to enhance communication. These four components are symbols, aids, techniques and/or strategies.

Most people who rely on AAC can benefit from the ongoing services of speech-language pathologists and other professionals. Evidence-based practice using observational methods, baseline data collection, language activity monitoring, and automated performance measurement tools yields the most effective results. Today's growth in rehabilitation services and distance learning are opening up new venues for intervention.

When people who rely on AAC have the benefit of a methodical and scientific process in the selection and application of an AAC system, they also have the highest potential for personal achievement. Those who encounter difficulty communicating via speech cross the life span from the young child to the older adult.
The injury epidemiology of infants and toddlers in Qatar
Authors: Consunji Rafael , Peralta Ruben Rosario , Al Thani Hassan , Latifi Rifat
Published: October 2012

Background and Objectives:
The epidemiology of child injuries among infants and toddlers (IAT) in Qatar has not been fully described. This study will analyze the injury epidemiology of fatal and non-fatal injuries in IAT and provide recommendations for targeted injury prevention programs for IAT in Qatar.

Method:
Data from the Qatar statistics authority (QSA), Hamad Medical Corporation (HMC) Trauma Registry and the mortuary for the years 2009 and 2010 were collected and analyzed. All injuries and injury mortalities to children ages 0-4 were included.

Results:
For IAT, one in thirteen (7.7%) deaths is caused by injuries with slightly more males (55%) affected. The leading fatal mechanisms were motor vehicle crashes (MVC's) (45%), followed equally by drowning, falls, burns and poisoning. Every year, there are 170 IAT admissions to the Trauma Center of HMC for severe injuries. Males comprise 70% of admissions, with a median age of 2.67 years, 17% were <1 year old. Mean injury severity score (ISS) was 6.2, median ISS was 4. Mean LOS was 4.57 days, median was 2 days. The leading reasons for admission were falls (43%), burns (25%), pedestrian (12%) and passenger (10%) MVC's. The majority (66%) of the injuries occurred at home. The mortality rate of admissions was 2.1%, 71% were males. MVC's were the leading cause of death (57%), equally divided between pedestrians and passengers, and falls happening at home caused 43% of deaths.

Conclusions:
Two-thirds of severe injuries to IATs happen at home where they are supposed to be safest and under the constant supervision of a responsible adult. While the majority of them are non-fatal, the leading mechanisms, falls and burns, can often lead to lifelong disability. These injuries can contribute to significant developmental delays and psychiatric trauma in IATs and considerable costs to the state.

Home safety education is a necessity for families with IATs. Educating families and caregivers on the appropriate environmental modifications in the home to prevent falls and burns must be a priority. The improved surveillance of child injuries and surveys of home conditions in Qatar is needed to form the basis for subsequent actions in this field.
Stable isotope labeling with amino acids in cell culture (SILAC) of human embryonic stem cells under chemically defined culturing conditions
Authors: Liberski Albert Ryszard , Rahman Zahra H. , Al-Noubi Muna N. , Dib Shaima Salah , Billing Anja , Raynaud Christophe , Tabrizi Jeremie Arash Rafii , De Melo Braga Marcella Nunes , Schulz Melanie , Engholm-Keller Kasper , Larsen Martin Røssel , Graumann Johaness
Published: October 2012

Background and Objectives:
Metabolic labeling with stable isotopes remains a prominent technique for comparative quantitative proteomics and stable isotope labeling with amino acids in cell culture (SILAC) is the most prominent approach used. However, despite its power the approach traditionally is limited if applied to complex tissue culture regiments as those required for human embryonic stem cells (hESC). Classic hESC culture is based on use of mouse embryonic fibroblasts (MEFs) for conditioning the cell culture medium or as a feeder layer. As a result the possibility of xenogeneic contaminants, contribution of unlabeled amino acids, inter-laboratory variability of MEFs and the trick complexity of the culture system are all concerns when using SILAC and beyond.

Methods:
We applied high accuracy LC-MS/MS analyses to evaluate the SILAC labeling efficiency of the hESCs cultured in the new SILAC- hESCs culture system.

Results:
The analysis yielded over 15,00 distinct hESC proteins with more than 99% accuracy of identification as estimated by reverse database searching. The efficiency of labeling was estimated to be higher than 99% for lysine and arginine; moreover, SILAC-labeled hESCs maintained undifferentiated self-renewal status.

Conclusions:
Here we use an enhanced feeder-free SILAC culture system based on a customized chemically defined SILAC-medium and a modified culture protocol to overcome these limitations and achieve reproducible labeling in a process easily scaled to proteomic protein requirements. The protocol is expected to greatly enhance the usability of quantitative proteomics as a tool for the study of mechanisms underlying hESC differentiation and self-renewal.
Relationship between plasma vitamin D level and cardiometabolic disease risk factors
Authors: Badawi Alaa , Garcia-Bailo Bibiana , Sadoun Eman , Da Costa Laura , Arora Paul , Al Thani Al Anoud M. , El-Sohemy Ahmed , Al Thani Mohamed H.
Published: October 2012

Background and Objectives:
Vitamin D is thought to modulate cardiometabolic disease risk through effects on an array of disease-associated pathways, such as glucose and lipid metabolism and inflammation. Although vitamin D insufficiency is thought to play a role in the susceptibility to cardiometabolic disease, the association between the two conditions is yet to be investigated in both men and women from the general population.

Methods:
Subjects (n= 1,928, age range 16-79 yrs) from Canada were examined. Plasma 25-hydroxyvitamin D [25(OH)D] by month of clinic visit were plotted for men and women to examine the monthly fluctuation patterns. Linear regression models adjusted for sex, waist circumference, physical activity, hormone use, and season of clinic visit examined the linear associations between 25(OH)D and cardiometabolic biomarkers [glucose, insulin, HOMA-IR, triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total:HDL-C ratio, apolipoprotein(apo)A1, apoB] and biomarkers of inflammation [C reactive protein (CRP), fibrinogen, and homocysteine]. Analyses were repeated separately for men and women.

Results:
Monthly variation in 25(OH)D was noted for both men and women, with mean levels fluctuating more widely throughout the year in men (50 to 80 nmol/L) than in women (60 to 75 nmol/L). Significant inverse associations with 25(OH)D were noted for insulin (β= -0.16, p=0 .003), HOMA-IR (β= -0.18, p= 0.002), triglycerides (β= -0.21, p= 0.004), total cholesterol (β= -0.31, p= 0.046), LDL-C (β= 0.09, p= 0.02), and total:HDL-C ratio (β= -0.09, p= 0.004). When the population was stratified by sex, significant inverse associations with 25(OH)D were observed for insulin (β= -0.21, p= 0.002), HOMA-IR (β= -0.24, p= 0.002), and triglycerides (β= -0.26, p= 0.01) among men, and insulin (β= 0.13, p= 0.05), HOMA-IR (β= -0.14, p= 0.03), total cholesterol (β= -0.34, p= 0.05), LDL-C (β= -0.10, p= 0.02), and total:HDL-C ratio (β= -0.10, p= 0.001) among women.

Conclusions:
Plasma 25(OH)D levels vary month-to-month, and fluctuate more widely in men than in women. Vitamin D may modulate multiple processes related to the cardiometabolic biomarkers and disease risk and may, thereby, play a role in disease prevention.
Sexuality education and determinants of perceived sex refusal skills among Lebanese adolescents
Authors: Kouyoumjian Silva Parsegh , DeJong Jocelyn , Afifi Rima , Zurayk Huda
Published: October 2012

Background and Objectives:
Globally around half of new HIV infections occur in the age group 15-24. New reported cases of HIV/AIDS in Lebanon show that a younger age group (20-30) is being affected more than ever before. Lebanon is moving forward in implementing a national sexuality education curriculum in all public schools, as a mechanism for raising awareness and for preventing sexually transmitted infections (STI) including HIV among adolescents. However, little is known about adolescents' actual sexual behavior, the extent to which students are confident of their refusal skills, and the factors that determine these. Young adolescents, who have limited sexual knowledge and experience, may have difficulty in adopting the appropriate protective behavioral responses to prevent negative health outcomes including STI and HIV infection.

Methods:
This research identified the prevalence and risk factors for perceived sex refusal skills among Lebanese adolescents in grades 7-9 in public and private schools using the nationally representative Lebanon Global School Health Survey.

Results:
Results indicated that more than 40% (50.4% of boys and 34.8% of girls) of students did not feel confident that they could tell someone they did not want to have sexual intercourse with them. Multivariate logistic regression analysis indicated that being female, older and having close parental supervision predicted having perceived sex refusal skills among Lebanese adolescents. Moreover, having knowledge and/or education about risky behaviors was the strongest predictor for having perceived sex refusal skills among Lebanese adolescents.

Conclusion:
This study contributes to the limited literature on perceived sex refusal skills in Lebanon, the Middle East and North Africa. A number of recommendations for research and prevention programs can be drawn from this research. Advocacy efforts should target policy makers to ensure that policies are reviewed to support comprehensive sexuality education in Lebanese schools because of identified vulnerabilities of sexual violence, low levels of education or knowledge of risky behaviors including HIV risk, and low levels of perceived sex refusal skills.
New frontiers for human risk assessment following exposure to chemical/environmental mutagens: State of the art testing for detecting causes of cancer
Authors: Darroudi Firouz , Long Michael
Published: October 2012

Background:
Large numbers of chemicals (natural and synthetic, including human dietary food components) are tested each year worldwide for potential genotoxic properties to protect humans and the environment against the consequences of exposure to such chemicals (cancer, infertility, accelerated ageing, and instability of ecosystems). For primary screening, fast in vitro and in vivo tests are used, but their predictive value is limited to the fact that they reflect the metabolism in humans inadequately. A methodological basis for improved tests by the use of human HepG2 cell system was developed. HepG2 cells were used as metabolic activation system as well as target for evaluating DNA damage. HepG2 cells are proven to have the same Phase I and II enzymatic profiles as human hepatocytes.

Objectives:
To apply this cell system and series of updated biological assays such as chromosomal alteration, as well as state of the art genomic and proteomic assays to investigate and characterize a broad variety of compounds to which humans are exposed via diet or the environment, including polycyclic aromatic hydrocarbons, heterocyclic aromatic amines and acrylamide, nitrosamines, heavy metals, pesticides, plant constituents, mycotoxins, complex foods (beverages, plant juices), environmental mixtures (air and water), cytostatic drugs and nitrosamines.

Methods:
The method is illustrated in Figure 1.

Results:
The results can provide information on initial DNA damage, repair kinetic, biological consequences, gene- protein- and enzymatic-expression profiles. These outcomes are required to develop measures to protect humans against exposure to dietary and environmental genotoxins.

Conclusion:
The characterization of different classes of chemicals will contribute substantially to the assessment of their health risks for humans. The outcomes may also reveal the potential of specific dietary components that can serve as co- and anti-carcinogens. Furthermore, the potential of HepG2 cell system as an alternative to use of vertebrate animals in genotoxicity testing can be evaluated.
Lack of evidence of substantial hepatitis C virus (HCV) prevalence decline in Egypt in the last 20 years
Authors: Mohamoud Yousra Ali , Abu-Raddad Laith J.
Published: October 2012

Background:
Egypt has the highest hepatitis C virus (HCV) prevalence in the world. Numerous HCV prevalence studies have published various estimates from different Egyptian communities, suggesting that Egypt, relative to the other nations of the world, might be experiencing an intense ongoing HCV transmission.

Objective:
To investigate the trend in HCV prevalence among the general population in Egypt with respect to time.

Methods:
We conducted a time-trend analysis to assess the trend in HCV prevalence using a multivariate linear regression model and adjusting for the different sub-groups in the general population. Data used for this analysis were extracted from relevant studies identified via a systematic review of HCV in Egypt.

Results:
Our results suggest that there is no evidence of a statistically significant decline in HCV prevalence over time (p-value: 0.572). HCV prevalence in the general population declined at a rate of only -0.11% per year (95% CI: -0.49 to 0.27).

Conclusions:
Our results do not support a decline in HCV prevalence over the last two decades even though Egypt's population has nearly doubled in the past two to three decades. This suggests that substantial HCV transmission might be still ongoing today. Policymakers, and public health and medical care stakeholders need to introduce and implement further prevention measures targeting the routes of HCV transmission in this country.