bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular modeling of mutations of the human cardiac troponin T hotspot codon 102 associated with hypertrophic cardiomyopathy in Egypt
Authors: Yacoub Magdi , Krishnamoorthy Navaneeth , Gajendrarao Poornima
Published: October 2012

Hypertrophic cardiomyopathy is the most common inherited heart diseases associated with a large number of mutations in several sarcomere proteins that regulate striated muscle contraction. The 3-dimensional structural and biophysical consequences of these mutations and their impact on the genotype-phenotype relationship remains poorly understood. Mutations in cardiac TroponinT (cTnT) have been reported to purport an increased risk of sudden cardiac deaths. Mutational hotspots such as codon 102 (Arg92 Moolman et al., 1997) of cTnT have been observed in several populations, including recently by our group in Egypt. In an attempt to explain this observation, we have performed molecular modelling of specific key mutations at codon 102, Arg102. The X-ray structure of the core domain of human cardiac troponin complex (cTnC, cTnI and cTnT) has been used for this study after constructing the missing regions. The resultant structure and the mutants were subjected to structural rigidity analysis and mutational modelling. In addition, molecular dynamics simulations were performed to understand the binding of functionally important calcium ions with the troponin complex. Our results suggest that the location of Arg102 in cTnT is instrumental to create a molecular bridge through hydrogen bonds (Figure) between secondary structural elements, in order to hold the core structure together. The loss of this molecular bridge by the key mutations (such as Arg102Leu) could produce conformational changes and affect natural binding of calcium ions, which are essential for regulation of muscle functions. This mechanism can explain the important structural consequences of mutations in this codon, associated with frequent progression of LV dysfunction, as well as the occurrence of ventricular arrhythmias secondary to the intracellular consequences of profound energetic and Ca++ handling derangement.
Towards understanding molecular mechanisms of calficic aortic stenosis (CAS)
Authors: Yacoub Magdi , Latif Najma , Chester Adrian
Published: October 2012

Recent studies have demonstrated that CAS is an active, regulated disease process akin to atherosclerosis, in which resident cells undergo remodeling and transformation. Normal valves harbor a low percentage of smooth muscle cells (SMCs) however their role in CAS is not defined.

We analyzed 12 normal and 22 calcified valves for early and late differentiated SMC markers by immunocytochemistry. Expression of myocardin and myocardin-related transcription factors (MRTFA/B) was analyzed. TGFβ1 was used to activate MRTFs in valve interstitial cells and transmission electron microscopy (TEM) was used to detect the presence of SMCs in areas of calcification.
The expression of SMC markers calponin, SM1, SM2 and SM22 was increased in all 22 calcified valves with caldesmon, SMC myosin, SMC α-actin and desmin increased in 40-91% of calcified valves. SMC markers were abundantly and aberrantly expressed in surface and microvessel endothelial cells and vasculature in 40% of the calcified valves. Normal valves showed expression of myocardin, MRTF-A and -B in the base of the ventricularis, similar to the pattern of SMC in normal valves. An aberrant expression of myocardin, MRTF-A and MRTF-B, was found in 71%, 53% and 67%, respectively, of calcified valves, in a similar pattern to the aberrant expression of SMC markers. In calcified valves the expression of MRTFs was nuclear in both valve interstitial cells and endothelial cells suggestive of activation. Nuclear expression of MRTF-A was increased by 11-fold in VICs treated with TGFβ1 (10ng/ml) (p<0.05). TEM of the fibrosa layer of calcified valves showed bundles of SMCs and SMC-derived foam cells.

In conclusion, SMCs are are aberrantly expressed around calcified nodules and in endothelial cells in CAS with myocardin and MRTFs, key regulators of SMC expression, abundantly expressed. These findings strongly suggest that the SMC phenotype plays an important role in the pathophysiology of CAS.
Biphasic nanofibrillar matrices for valve tissue engineering
Authors: Yacoub Magdi , Chester Adrian , Sohier Jerome
Published: October 2012

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.
Exposure to secondhand smoke among Qatari pregnant women
Authors: Mahfoud Ziyad , Al Nabti Al Reem , El Ghazar Sally , Oglat Ayah , El Taher Faten
Published: October 2012

Background:
The harmful effects of smoking during pregnancy on the health of the mother, fetus and newborn have been well documented in the literature. These include, low birth weight, prematurity and still birth. The negative effect of smoking on health is not restricted to active smokers as studies have shown that exposure to secondhand smoke (SHS) during pregnancy also poses risks on the mother and the fetus. To our knowledge there has not yet been any study that researched exposure to SHS among Qatari pregnant women.

Objectives:
The objectives are: 1) to estimate the prevalence and associated factors related to exposure to SHS during pregnancy among Qatari women and 2) to estimate the level of knowledge of health risks and attitudes towards tobacco smoking.

Methods:
A cross-sectional study using a convenience sample of Qatari pregnant women was done at the Women's Hospital which is the main hospital for deliveries for Hamad Medical Corporation, the largest health service provider in Qatar. We targeted pregnant women both in public and private clinics inside the hospital. A total of 357 women were approached and data were collected on 305 women, yielding a response rate of 85.4%. Data collection took place between January 2012 and May 2012.

Results:
A very high proportion (81%) responders reported exposure to SHS. Exposure outside the house was higher than that inside the house. Husbands were the main source of exposure to SHS inside the house and restaurants and cafés were the main places of exposure outside the house. Although women's knowledge about the harmful effects of exposure to SHS was high it was not associated with exposure status. Being in a smoke free house was a protective factor against exposure to SHS.

Conclusion:
Pregnant women, their fetus and new born are in danger due to exposure to SHS. Public health awareness interventions should target pregnant women and in particular their husbands. Moreover, there should be stricter implementation of smoking bans in restaurants and cafés.
Variability in HIV infectiousness across Sub-Saharan Africa
Authors: Chemaitelly Hiam , Abu-Raddad Laith J
Published: October 2012

Background & Objectives:
A recent randomized clinical trial, CAPRISA 004, reported levels of HIV incidence rate among general population women in South Africa that are comparable or higher than those observed among high-risk populations such as female sex workers, men who have sex with men, or injecting drug users despite low coital frequency. Understanding the factors leading to such high HIV incidence levels is critical for guiding prevention efforts. To this end, we have assessed the risk of HIV transmission among stable couples across a range of epidemic settings in Sub-Saharan Africa (SSA).

Methods:
We constructed a mathematical model describing the process of HIV discordancy in a population in the context of an HIV epidemic to estimate the risk of HIV transmission within stable partnerships. The model was parameterized using nationally representative demographic health survey data for 20 countries in SSA. Uncertainty and sensitivity analyses were performed to explore the robustness of our estimates to systematic biases in model parameters.

Results:
HIV incidence rate among discordant couples hovered around 10 per 100 person-years across SSA. A clustering based on HIV prevalence was observed with a median of 7.8 per 100 person-years in low HIV prevalence countries (<5%) compared to 18.4 per 100 person-years in high prevalence countries (>5%). HIV population prevalence explained 49% of the variation in HIV transmission, with every 1% increase in HIV prevalence implying an increase of 1.2 per 100 person-years in HIV infectiousness. The uncertainty and sensitivity analyses suggested that potential systematic biases are more likely to lead to a slight overestimation in HIV incidence rate particularly in high prevalence countries.

Conclusions:
Our results suggest that a variability in HIV infectiousness may have contributed to the contrasting HIV epidemic trajectories across Africa. The key drivers of this variability may include male circumcision, different circulating virus subtypes, sexually transmitted co-infections, tropical co-infections, hormonal contraception, and host genetics and immunology. The role of behavioral cofactors such as coital frequency and the uptake of condom use are less evident.
Protein PEGylation and gene DNA shuffling for the production of new protein therapeutics
Authors: Goda Sayed Kamel
Published: October 2012

Background:
Hepatitis C has emerged in recent years as a common cause of liver disease. An estimated 200 million people are thought to be infected worldwide. Hepatitis C virus (HCV) infection is characterized by viral persistence and chronic liver disease in approximately 80% of cases. Chronic HCV infection is curable by either a combination of interferon and ribavirin, or PEGylated interferon. Both drugs had been shown to inhibit the replication of the hepatitis viruses.

Objectives:
The work presented has two major objectives: 1) To clone, overexpress the interferon alpha2a and to produce the PEGylated form using codon optimized synthetic interferon alpha 2a; 2) To produce a novel variant of interferon and PEGylated interferon with ultra-activity.

Methods:
A synthetic gene coding for human interferon alpha 2a was codon-optimized and synthesized for maximum expression in E. coli using the vector pET28a.The recombinant protein was expressed and purified in the single step by Ni²+ charged column chromatography. The PEGylated interferon alpha 2a was prepared using the 40K polyethylene glycol. The purified product was confirmed using the MS and Moldi. DNA shuffling was performed to produce a novel variant of interferon.

Results:
Our work indicates that the enzyme was expressed to ~60% of the total host protein and that purification of the recombinant His-tagged protein could be achieved in a single step. The synthetic recombinant human interferon alpha2a expressed within this system was biologically active. We successfully then managed to produce a biologically active PEGlated interferon using a 40K polyethylene glycol.

In an attempt to produce a novel variant of PEGylated interferon we prepared libraries of DNA fragments of interferon alpha2a gene using the DNA shuffling techniques. These libraries will be screened for more active interferon. The novel characterized variants will then be PEGylated and molecular studies on the novel PEGylated interferon will be performed.

Conclusion:
Our work has not only shown that a biologically active PEGylated interferon could be produced from a codon optimized synthetic interferon but also demonstrated that one of the very expensive drugs could be produced locally with the saving of tens of millions of dollars every year.
Photo-cross-linked poly(alkylene-co-tartrate) biodegradable matrices for implantable controlled drug delivery and other biomedical applications
Authors: Abuhelwa Ahmad , Shaker Mohammed , Younes Husam M
Published: October 2012

Objectives:
To investigate the synthesis and in vitro characterization of a novel family of photo-cross-linked biodegradable poly(alkylene-co-tartrate) (PAT) for the purpose of their use in implantable drug delivery and tissue engineering applications.

Methods:
PAT prepolymers were first synthesized via polycondensation reaction of L-tartaric acid with alkylene diols of varying chain lengths (C6-C12) at 130°C for two hours under nitrogen atmosphere followed by one extra hour under vacuum to form PAT prepolymers. The purified prepolymers were then acrylated using an equimolar ratio of acryloyl chloride and triethylamine. Following purification, the acrylated poly(alkylene tartrate) prepolymers (APAT) of varying degrees of acrylation were photo-cross-linked to form the elastomers. The prepared prepolymers were characterized using Proton Nuclear Magnetic Resonance (1H-NMR), Fourier transform infrared (FTIR) analysis and differential scanning calorimetry (DSC). The PAT elastomers were also subjected to sol-gel content analysis and mechanical testing. The osmotic-driven release of protein drug from those elastomers was also investigated.

Results:
1H-NMR and FTIR analysis confirmed the chemical structure and the purity of the PAT prepolymers and confirmed the existence of the acryloyl moieties at the formed chains terminals. Osmotic driven release from PAT elastomeric matrices was found to be controlled by changing the osmotic activity of the loaded drug mix as well as the degree of macromers acrylation, without altering the release kinetics. The obtained photo-cross-linked elastomers were stretchable and rubbery and swell rather than dissolve in most of organic solvents. Mechanical properties were found to be dependent on the number of methylene groups in the chain of precursor diol and the crosslinking density of the elastomeric matrices.

Conclusions:
Biodegradable, polyester matrices were successfully prepared and characterized. The family of PAT biodegradable polyesters has promising use in drug delivery and other biomedical applications including tissue engineering.
Improving type 2 diabetic patient knowledge, attitude and practice towards diabetes selfcare by implementing a community-based interactive approach - diabetes mellitus strategy
Authors: Izham Mohamed , Hartayu Titien Siwi , Sri Suryawati
Published: October 2012

Background:
Community-based interactive approach-diabetes mellitus (CBIA-DM) is an active self learning method. CBIA is a method used for public education which emphasizes the active role of participants in looking for information. The intention of CBIA is to empower participants to seek and critically assess information about their treatment.

Objectives:
This study is aimed at improving type 2 diabetic patients knowledge, attitude and practice on diabetes selfcare by implementing the CBIA-DM strategy.

Methods:
This is a time series pre- and post-quasi-experiment with control group design. The intervention group underwent CBIA-DM strategy. There were two control groups: one group DM participated in Sunday meetings for physical activity together and two monthly regularly seminars, and the other group received normal care. Pre- and post-test KAP questionnaires were used as study instruments. Data was collected pre-intervention, immediately, one, three and six months post-intervention. The ranging scores for pre- and post-test questionnaires were: knowledge (0-18) and attitude (9-45), categorized as rational scales of the scores: good, fair and poor. Practicing in diabetes selfcare was assessed using 12 questionnaires, and categorized as: adhere and not adhere to DM selfcare. Effectiveness of CBIA-DM was evaluated based on the increasing number of participants with good knowledge and attitude levels, and adherence in practicing diabetes selfcare.

Results:
CBIA-DM group shows increasing number of participants in good level of knowledge from 40% (n= 30) up to 80% at M + 3 with scores significantly improved from 13.1 ± 2.4 up to 15.4 ± 2.0 (Wilcoxon test, p <0.05), attitude from 20% up to 50% at M + 3, with scores significantly improved from 33.5 ± 4.1 up to 34.9 ± 6.2 (p= 0.031) and increasing number of participant adherence to all variables of DM selfcare at M + 6 post intervention.

Conclusions:
CBIA-DM strategy is effective to improve diabetic patient knowledge, attitude and practice on diabetes selfcare. Repeating and improving the strategy program is needed to verify the impact.
Gene regulatory network inference using information theoretic methods
Authors: Noor Amina , Serpedin Erchin , Nounou Hazem , Nounou Mohamed , Qaraqe Marwa , Chouchane Lotfi , Mohamed Nady
Published: October 2012

Background & Objectives:
Gene regulatory network inference is a problem of prime importance in the budding field of systems biology and bioinformatics. The process which uses the information present in the genes to produce functional gene products is termed gene expression, and it can be measured using the microarray technology. The scope of this work is to propose a series of information theoretic algorithms which utilize the gene expression data to reverse engineer gene regulatory networks.

Methods:
Using information theoretic tools, this work proposes several algorithms to indicate how the genes are interacting with each other in a biological system. One of the advantages associated with these information theoretic algorithms is that they work with minimum assumptions. The concept of mutual information is a fundamental quantity in information theory that is used extensively in this work to measure the degree of dependency between genes. There are situations when two genes are interacting but only via an intermediate gene. By employing data processing inequality and condition mutual information, this work shows the possibility to identify such indirect interactions.

Results:
The computer simulations illustrate that the proposed information theoretic methods provide some of the most robust algorithms for inferring the topology of gene regulatory networks. While estimating the genetic interactions, it is necessary to put a constraint on the complexity of the network so as to avoid over-fitting the network. To this end, minimum description length principle and Bayesian information criterion are used for model selection. Results performed on both synthetic and realistic gene regulatory networks attest the superior performance of the proposed algorithms.

Conclusions:
This work describes different information theoretic approaches for determining the possible interactions between genes using gene expression data. The performance metrics used to assess these algorithms are also discussed. It is concluded that information theoretic methods represent powerful tools for inference of gene regulatory networks.
Non-acute responses of hematological and molecular markers to intermittent hypoxic exposure and physical exercise in hot environment
Authors: Voss Sven , Nikolovski Zoran , Bucheit Martin , Racinais Sebastian , Coutts Aaron , El Rayess Mohammed , Orie Nelson , Aljaber Mashael , Muhammed Ali Ameena , Bakhamis Aysha , Mohamed Ali Vidya , Alsayrafi Muhammad
Published: October 2012

Background & Objectives:
Both exercise and hypoxia acutely elicit changes in systemic growth factors and cytokines that mediate increases in erythropoiesis, angiogenesis and, perhaps, arteriogenesis. To what extent the down-stream responses to these interventions are inter-related is, as yet, unclear. A role for circulating micro RNAs (cmiRNAs) in the regulation of these processes is a novel prospect. Thus the aims of this study are to investigate the effect of hypoxia and exercise training on relevant growth factors and cmiRNAs in a healthy human cohort.

Methods:
18 healthy, Caucasian, male, elite athletes participated in this study. The project was designed as a parallel, two-groups, matched, randomized, longitudinal (pre-, mid-, post-test), two week intervention. One group was exposed to hypoxia (15 hours/day) the other stayed in a normoxic environment. Both groups performed physical exercise in a 10°C hotter environment than usual. The exercise was standardized for both groups and the daily work load was monitored. Blood was sampled under fasting conditions in the morning, to avoid any effects of acute exercise. Hemoglobin (Hb), reticulocytes, erythropoietin, vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), cmiRNAs 144, 146a, 221, 222 were tested in blood and sera.

Results:
In the normoxic group decreases from pre- to mid- and post-test were found for Hb (p=0.011, p=0.002) and IL-6 (p=0.028, p=0.008). However, in the hypoxic group several changes were apparent. In this group Hb changed at the pre- to mid-test (p=0.013), reticulocytes also increased from pre- to mid-test (p=0.066), erythropoietin increased from pre- to mid- and post-test (p=0.008, p=0.008). VEGF also showed a tendency to increase from pre- to mid-test (p=0.085) and increased from pre- to post-test (p=0.011). The 2-ΔΔCT values for cmiRNAs 221 and 222 showed an increasing trend at the post-test time point but did not reach statistical significance.

Conclusions:
Hypoxia stimulated several cytokines and growth factors mediating erythropoiesis and angiogenesis, which might have counteracted the plasma volume related decrease in Hb in the normoxic group. While there were changes in cmiRNAs (221 and 222) these were not statistically significant, perhaps due the small study cohort, which is currently being expanded to confirm these results.
Dietary composition and postprandial inflammation: Implications for human health
Authors: Brown Amanda , Olson Ken , Khaled Mohammad
Published: October 2012

Inflammation, in general, has been found to be associated with many human health complications. Postprandial inflammation, provoked soon after ingesting a meal, is transient in duration, but with dreadful consequences on human health over a period of time depending on the compositions of the meal. However, many populations, particularly in the Western countries, are in a constant postprandial state, which is likely to initiate insulin resistance (IR) resulting in type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). Postprandial inflammation is dependent on the food quality and quantity, mostly in terms of its energy/calorie content and its nutritional value. Micronutrients, such as minerals and vitamins, constitute the nutritional value of a food, while macronutrients, such as carbohydrate, protein and fat/lipid, are basically the sources of its energy/calorie content. Since energy content varies significantly between carbohydrates (4 kcal/g) and fats (9 kcal/g), the objective is, therefore, to assess postprandial inflammation of an isocaloric, isonitrogenous high carbohydrate (66%) and low fat (20%) diet (HC) versus a high fat (56%) and low carbohydrate (30%) diet (HF), by measuring diet-induced postprandial thermogenesis (DIPT). Healthy, never-obese, postmenopausal, Caucasian female subjects (n=12) participated in this study for 3 weeks each in a crossover design. Fat-free mass (FFM) and fat mass (FM) were measured by under-water weighing before and after each diet. Resting metabolic rate (RMR) was assessed fasting and for five 40-minute periods over a 6 hours DIPT after ingesting 14.3 kg/FFM of either HC or HF diet. A low respiratory quotient (RQ), during the measurement of DIPT, is usually indicative of lipid peroxidation, an important index of inflammation. RQ after ingesting HC diet was significantly higher in this study, while it was significantly lower for HF diet, thus indicating a higher inflammatory response due to fat. A significant elevation of free fatty acid (FFA) was also observed after ingesting HF diet, which is well-known to be associated in the pathophysiology of T2DM, a significant risk factor for CVD. Further studies are necessary to understand the role of postprandial inflammation in human health.
Acute effects of blood transfusion on pituitary gonadal axis and sperm parameters in young males with sickle cell disease (SCD): A pilot study
Authors: Yassin Mohamed Abdeldaem , Soliman Ashraf Tawfiq , Alawwa Ahmed Said , Elayoubi Hanadi Rafii
Published: October 2012

Objective:
To evaluate semen parameters and measure serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) concentrations before and 7 days after packed red cell transfusion (PCTx) in adults with sickle cell disease (SCD).

Methods:
This prospective study investigated 18 young adults with transfusion-dependent SCD, aged 20.7 +/- 2.88 years, with full pubertal development (Tanner's stage 5) (euogonadal), and capacity to ejaculate. Their serum ferritin levels were 1488 +/- 557ng/ml. Basal serum concentrations of FSH, LH, T and IGF-I were evaluated before and 7 days after packed red cell transfusion (PCTx). We studied the effect of PCTx on semen parameters and the endocrine functions in these 18 patients with SCD.

Results:
Following PCTx, a significant increase of Hb from 8.5 +/- 1.17 g/dl to 10.5 +/- 0.4 g/dl was associated with increased testosterone (12.3 +/- 1.24 nmol/L to 14.23 +/- 1.22nmol/L and gonadotropin concentrations. Total sperm count increased significantly from 87.4 +/- 24.6 million/ml to 146.2 +/- 51.25 million/ml total progressive sperm motility (TPM) from 40.8 +/- 11.1 million/ml to 93.4 +/- 38.3 million/ml, and rapid progressive sperm motility progressive motility (RPM) increased from 29.26 +/- 8.75 million/ml to 67.4 +/- 29 million/ml. After PCTx the total sperm count, TPM and RPM were significantly higher in the ETx group versus the TTx group.

Before and after PCTx, testosterone concentrations were correlated significantly with sperm total count, volume, TPM and RPM (r= 0.53, 0.55, 0.42 and 0.38 respectively, p= 0.01). Before and after PCTx, hemoglobin concentrations were correlated significantly with sperm count, TPM, RPM and percentage of sperms with normal morphology (r= 0.60, 0.69, 0.66 and 0.86 respectively, p <0.001)

Conclusion:
Our study suggests that in males with SCD, blood transfusion associated with significant acute enhancement of sperm parameters and with an increased concentration of testosterone, LH and FSH. Improvements of sperm parameters were significantly higher in the exchange transfusion (ETx) group versus the top-up (TTx) group. These 'acute' effects on spermatogenesis are reached with an unknown mechanism(s) and suggest a number of pathways that need further human and/or experimental studies.
Prognosis of neurogenic dysphagia by neuromuscular electric stimulation (NMSE) therapy versus NMSE coupled with conventional swallowing training in subacute cases in Qatar
Authors: Ahmad Amal Idres , Husain Mohmad Sajed
Published: October 2012

To study the effects of VitalStim therapy coupled with conventional swallowing training on recovery of neurogenic dysphagia, a total of 30 dysphagia patients were randomly selected among subacute post-traumatic brain injury and cerebrovascular accident cases. The cases were evenly divided into two groups: neuromuscular electric stimulation (NMSE) group, and NMSE plus conventional swallowing therapy group. Before and after the treatment, swallowing function was evaluated by using fiberoptic endoscopic evaluation of swallowing (FEES) test and swallowing ability function evaluation (SAFE). Outcomes were analyzed for changes in oral and pharyngeal phase dysphagia severity, diet consistency and improvement from non-oral to oral intake. There were significant differences in the SAFE score in each group before and after treatment. After 8-week treatment, the SAFE score was significantly greater in the NMSE therapy plus conventional swallowing training group than in the NMSE therapy group. It was concluded that VitalStim therapy coupled with conventional swallowing training was conducive to recovery of post-stroke dysphagia.
An innovative thermometric "Stress Test" for early diagnosis of acute charcot
Authors: Najafi Bijan , Grewal Gurtej , Sayeed Rashad , Menzies Robert , Talal Talal , Zirie Mahmoud , Bharara Manish , Armstrong David
Published: October 2012

Background & Objectives:
Charcot neuroarthropathy (CN) is a devastating complication of diabetes. It has two-fold higher rate of major amputation compared to those without CN. Unfortunately, to date, there is no pathological marker or diagnostic criterion for it and diagnosis relies on pattern recognition and clinical intuition. Not surprisingly, the diagnosis can be missed up to 95% of the time and the average diagnostic delay has been estimated at almost 7 months. Recent studies reported asymmetric plantar temperature differences secondary to inflammation as a hallmark for the diagnosis and treatment response of Charcot foot syndrome. However, little attention has been given to temperature response to activity.
Methods:
Fifteen individuals with acute CN and 17 age-matched non-CN participants with type 2 diabetes and peripheral neuropathy were recruited. All participants walked for two predefined paths of 50 and 150 steps. A thermal image was acquired at baseline after acclimatization and immediately after each walking trial. The plantar temperature (PT) response as a function of number of steps was examined using a validated wearable sensor technology. A custom image processing toolbox was designed to characterize the plantar temperature response to activity.
Results:
During initial activity, the PT was reduced in all participants, but the temperature drop for the non-affected foot was 1.9 times greater than the affected side in CN group (p=0.04). Interestingly, the PT in CN was sharply increased after 50 steps for both feet, while no difference was observed in non-CN between 50 and 200 steps.
Conclusions:
The observed differential thermal response to walking initiation between Charcot and non-Charcot feet warrants future investigation to provide further insight into the correlation between activity dosing and thermal response. It may also lead to a valuable insight into identifying an "inflammatory trigger" that may ultimately provide an early warning sign or increased sensitivity for subsequent unilateral or bilateral CN development or clinical expression of foot ulcer. These results also support that managing modulating duration of continuous steps and or prolonged standing during daily activity could be helpful for reducing the trauma in patients with CN or patients at risk of diabetic foot ulcer.
Association between obesity, cardiometabolic disease biomarkers and innate immunity-related inflammation: Relevance of vitamin D.
Authors: Badawi Alaa , Da Costa Laura , Arora Paul , Garcia-Bailo Bibiana , Sadoun Eman , Al Thani Al Anoud M. , Al Thani Mohamed H. , El-Sohemy Ahmed
Published: October 2012

Background and Objectives:
Obesity is associated with a state of chronic inflammation and increased cardiometabolic disease risk. The present study examined the relationship between body mass index (BMI) and cardiometabolic and inflammatory biomarkers among normal weight, overweight, and obese subjects.

Methods:
Subjects (n = 1,805, aged 18 to 79 years) from Canada were examined for associations between BMI, cardiometabolic markers [apolipoprotein (Apo) A1, ApoB, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol, total:HDL-C ratio, triglycerides, and glycosylated hemoglobin (HbA1c)], inflammatory factors [C-reactive protein (CRP), fibrinogen, and homocysteine), and 25-hydroxyvitamin D [25(OH)D]. Bootstrap weights for variance and sampling weights for point estimates were applied to account for the complex survey design. Linear regression models adjusted for age, sex, physical activity, smoking status, and ethnicity (in addition to season of clinic visit for vitamin D analyses only) were used to examine the association between cardiometabolic markers, inflammatory factors, and BMI in adults.

Results:
All biomarkers were significantly associated with BMI (P≤0.001). ApoA1 (β= 0.31, P<0.0001), HDL-C (β=-0.61, P<0.0001), and 25(OH)D (β=-0.25, P<0.0001) were all inversely associated with BMI, while all other biomarkers showed positive linear associations. Different patterns of significant associations were noted for all biomarkers among normal weight, overweight, and obese groups, excluding CRP which was consistently correlated with BMI and showed a significant positive association in the overall population (β=2.80, P<0.0001) and in the normal weight (β=3.20, P=0.02), overweight (β=3.53, P=0.002) and obese (β=2.22, P=0.0002) groups. Interestingly, plasma vitamin D levels were significantly inversely correlated with BMI (β=-0.25±0.06, P<0.0001).

Conclusions:
There is a distinctive profile of cardiometabolic and inflammatory biomarkers that emerges with obesity as BMI increases from normal weight to obesity. Elucidating these profiles may permit developing an effective approach for early risk prediction of cardiometabolic disease and its prevention based on modulating the corresponding metabolic phenotype in each BMI stage., e.g., by micronutrients such as vitamin D.
Epidemiology of football injuries in Asia: A prospective study in Qatar
Authors: Eirale Cristiano , Farooq Abdulaziz , Smiley Faten , Tol Johannes , Chalabi Hakim
Published: October 2012

Objectives:
To investigate the incidence, characteristics and patterns of football injuries at club level in Qatar.

Design:
Prospective cohort study.

Methods:
Data were prospectively collected from the first division football league clubs in Qatar, in accordance with the international consensus statement on football injury epidemiology. An injury was defined as any physical complaint sustained during football activity resulting in the inability to participate fully in the next training or match. Individual injuries and exposure of each player were recorded by the medical staff of each team over one season.

Results:
A total of 217 injuries were recorded, with an injury rate during matches of 14.5/1000 h (95% CI: 11.6-18.0) compared with 4.4/1000 h during training sessions (95% CI: 3.7-5.2). More than one third of all injuries were muscle strains (36.4%). Hamstring strains (54.4% of all muscle strains) exhibited a higher incidence than all other injury types (p < 0.001). The thigh was the most frequent injury location (41.9%, p < 0.001). Re-injuries (15% of total injuries) were mainly comprised of muscle strains associated with a higher severity compared with new injuries.

Conclusions:
Despite the different environmental, social and cultural setting, our findings are comparable with previous data from a European club football, confirming the previous finding at national team level that there are no regional peculiarities of football injuries in this part of the Asiatic continent. The relatively high overuse injury incidence rate and the high recurrence rate for (severe) thigh muscle strains, especially during games, warrants prevention strategies.
Akt-activated endothelial cells enhance self-renewal, stemness, resistance to therapy, and metastasis in breast cancer
Authors: Ghiabi Pegah , Pasquier Jennifer , Guerrouahen Bella , Rafii Tabrizi Arash
Published: October 2012

Recently, the role of tumor microenvironment (niche) in regulating cancer progression has been indicated. Tumor microenvironments consists of tumor vasculature, bone marrow mesenchymal stem cells, immune cells and the components of the extracellular matrix. It is believed that the phenotypic advantages acquired by tumor cells are partly the outcome of their interaction with their niche. Endothelial cells are the building blocks of tumor vasculature and have lately been shown to have additional benefits than merely a conduit for supplying oxygen and nutrients. Here, we intend to demonstrate the critical role of the Akt-activated endothelial (E4ORF1) cells on breast cancer development, survival and spreading. The effect of E4ORF1 cells on breast cancer (BC) and breast cancer stem cells (BCSC) self-renewal was assessed by co-cultivating E4ORF1 with MDA-MB231 and MCF-7 BC cells under adherent and suspension conditions. BCSC enrichment by E4ORF1 cells was measured by analyzing the CD44+/CD24Low/- population of BC cells by flow cytometry as well as by evaluating the expression of pluripotency markers by RT-PCR. BCSCs resistance to treatment was investigated by addition of metformin and determining BCSC proliferation with/out E4ORF1. The role of E4ORF1 on BC cell metastasis was shown by migration and adhesion potential of BC cells with/out E4ORF1 cells. Our results demonstrated a 5-fold increase in the self-renewal capacity of BC cells and BCSCs in the presence of E4ORF1. Also, E4ORF1 was able to promote stemness in BC cells as was shown by significant increase in CD44+/CD24Low/- BCSC population and the up-regulation of pluripotency markers. Moreover, BCSCs survived drug treatment by 2.5 folds in the presence of E4ORF1. Besides, BC cells showed enhanced invasion/adhesion property when exposed to E4ORF1 cells. Our data suggest a major role for E4ORFl cells in BC progression, stemness, resistance and metastasis. This characteristic of E4ORF1 cells in maintaining BC cells can be exploited in developing novel anti-cancer therapy to combat BC in a more effective way.
Effects of lipotoxicity and diabetes on hepatocyte function
Authors: Sedeeq Alhasan , Al Hajri Mohamed , Omar Mennatallah , Marei Isra , Triggle Christopher , Ding Hong
Published: October 2012

Background and Objectives:
Obesity is a major risk factor for the development of liver disease and diabetes and there is currently a pandemic of diabetes that is associated with a very high incidence of non-alcoholic fatty liver disease and consequent deregulation of liver function. The overall objective of this project is to determine whether non-alcoholic fatty liver disease and hyperglycemia affect calcium homeostasis via altering the expression of the plasma membrane calcium release-activated calcium channel protein, Orai1, the endoplasmic reticulum calcium sensor protein, STIM1, and store-operated Ca2+ entry, SOCE, in rat hepatocytes.

Methods:
Rat H4IIE liver cells exposed to amiodarone were used as a cell culture model of steatosis and Western Blot, RT-PCR and fura-2 techniques were used to assess protein, mRNA and changes in Ca2+ homeostasis, respectively. Rat H4IIE liver cells were grown either in normal glucose (5.5 mM) or high glucose (25 mM) for 24 hours, then each group was treated with either vehicle (methanol), amiodarone for 24 hours, or amiodarone for 24 hours followed by normal glucose for another 24 hours. Intracellular calcium [Ca2+]i was measured using fura-2am.

Results:
Expression of both STIM1 and Oai1 increases after treating with amiodarone for 24 hours in both normal and high glucose, but decreases after treating with amiodarone for 24 hours when followed by normal glucose treatment. In addition high glucose enhances SOCE whereas amiodarone treatment suppresses SOCE.

Conclusion:
Changes in the concentration of intracellular Ca2+ in hepatocytes play a central role in mediating the actions of insulin, glucagon, catecholamines and other hormones and growth factors on carbohydrate, lipid and protein metabolism in the liver. Both hyperglycemia and steatosis result in alterations in Ca2+ homeostasis suggesting that such changes may be contributing factors by which hyperglycemia, obesity and fatty liver result in insulin resistance in the liver. The results from this UREP project may lead to a better understanding of the mechanisms whereby diabetes, obesity and fatty liver disease result in liver malfunction.
Assessment of service quality in public and private pediatric healthcare in Qatar
Authors: Al-Shouli Hana Yousef , Faisal Mohd Nishat
Published: October 2012

Objective:
The purpose of this study is to assess the quality of pediatric services in public and private hospitals in Qatar.

Methods:
The objectives were achieved using a modified SERVQUAL scale. Data from 179 participants who visit public/private hospitals in Qatar were analyzed to find the gaps between expectations and perceptions.

Results:
The findings revealed that customers' expectations exceeded their perceptions, meaning that they were dissatisfied with the level of healthcare services rendered by public and private healthcare settings. The results indicated that there was a negative quality gap on each service quality scale dimension. Responsiveness and empathy variables had their highest service gaps score in public hospitals; reliability and assurance received their highest negative scores in private hospitals.

Conclusions:
The managers in these hospitals should work towards improving the quality of their services particularly the responsiveness and empathy dimensions.
Enhancing the efficiency of direct reprogramming into cardiac myocytes by defined transcription factors
Authors: Al Jurdi Ayman , Schachterle Will , Rafii Shahin
Published: October 2012

An efficient method to generate cardiac tissue from other tissues has great therapeutic potential for patients suffering from cardiovascular disease. Pluripotent stem cells, such as embryonic stem (ES) cells, and so-called induced pluripotent stem (iPS) cells can be differentiated into multiple cell types, including cardiac myocytes.
However, therapeutic use of these cells has several important risks, including cancer as well as loss of differentiated cell identity and function or "drift." Transdifferentiation, the generation of cell types from other differentiated cell types, is an attractive alternative because it poses little risk of cancer and may give rise to cells whose identity
is locked in. However, the direct reprogramming of adult fibroblasts into cardiac myocytes is inefficient and the transcription factors that drive this process are unknown.
To circumvent these hurdles we hypothesized that fetal derived cells may be more amenable to reprogramming into cardiac myocytes with defined transcription factors. To this end, fetal derived fibroblasts and mesenchymal cells were transduced with transcription factors that have been shown to play a role in myocyte specification and maintenance, including GATA4, Mef2c, Tbx5 and Nkx2.5. To test this hypothesis, the transcription factors were cloned into lentiviral vectors, which were used to infect fibroblasts and mesenchymal cells. Infected cells were then cultured in different media. To assess the efficiency of the reprogramming, RNA was extracted from infected and uninfected cells, and quantitative RT-PCR was used to evaluate the expression levels of the transcription factors and known cardiac genes. We expected to observe higher levels of the transcription factors and cardiac markers in the infected cells relative to the uninfected cells.

The results showed that the infected cells expressed higher levels of the transcription factors and a few cardiac markers relative to the uninfected cells. However, due to the small increase in the levels of only a few cardiac markers, the reprogramming was concluded to be inefficient. To make the reprogramming more efficient, other as yet unrecognized transcription factors possibly in the GATA family of transcription factors and culture conditions are currently being considered.
Characterization of insulin signaling pathway in calnexin knockout cells
Authors: Musa Samah , Liberska Aleksandra , Massaeli Hamid , Mesaeli Nasrin
Published: October 2012

Background:
Calnexin is a lectin-like chaperone in the endoplasmic reticulum (ER) lumen, which along with calreticulin are involved in folding, maturation and trafficking of many glycoproteins. Insulin receptor and glucose transporters are among some of the proteins which are synthesized and folded in the ER. Previously, calreticulin was reported to play a role in the folding of GLUT-4 transporter as well as its stability. Furthermore, our lab reported that loss of calreticulin function results in increased insulin receptor synthesis, increased phosphorylation of Akt upon stimulation by insulin and increased glucose uptake. To date no data are available on the changes in insulin receptor pathway upon loss of calnexin chaperone.

Objectives:
The aim of this study is to examine changes in insulin receptor expression and insulin-mediated phosphorylation of Akt upon loss of calnexin function.

Methods:
Mouse embryonic fibroblast cells were serum starved overnight, then stimulated with insulin for 10 mins at 37°C. Cell lysate were prepared and Western blots with antibodies of different proteins in insulin signaling pathways were performed.

Results:
Our results showed a significant increase in insulin receptor expression in calnexin deficient cells. Furthermore, we observed a significant increase in the phosphorylation of Akt illustrating activation of insulin receptor pathway upon loss of calnexin function.

Conclusions:
In conclusion our data illustrates that loss of either of lectin like chaperones (calreticulin and calnexin) results in the activation of insulin receptor pathways via release of a negative suppressor of insulin receptor gene expression. Further research is needed to decipher the mechanism of this regulation.