BACKGROUND-Inherited arrhythmias may underlie intrauterine and neonatal arrhythmias. Resolving the molecular genetic nature of these rare cases provides significant insight into the role of the affected proteins in arrhythmogenesis and (extra-) cardiac development.

CTEN/TNS4 is a member of the Tensin gene family. It localizes to focal adhesions and induces cell motility. The mechanisms regulating Cten expression are unclear although we have shown regulation by Kras in the colon and pancreas. In normal mammary cell lines, it is reportedly upregulated by epidermal growth factor receptor (EGFR) and STAT3 signalling and upregulation is accompanied by downregulation of Tensin 3 (Tensin switch). In this study, we investigated the roles of EGFR and STAT3 signalling in the regulation of Cten in colorectal cancer (CRC). In addition, we investigated calpain--a regulator of focal adhesion-associated proteins whose relevance to Cten has not been investigated. CRC cell lines were stimulated with epidermal growth factor (EGF). This resulted in an increase in Cten and Tensin 3 protein. Kras was knocked down and this resulted in downregulation of Cten and Tensin 3. We next investigated the role of STAT3 signalling. Activation and knockdown of STAT3 resulted in downregulation and upregulation, respectively, of Cten. Inhibition of calpain resulted in upregulation of both Cten and Tensin 3. As the regulators of Cten also seemed to regulate Tensin 3, we tested the interaction between Cten and Tensin 3. Cten was forcibly expressed or knocked down resulting, respectively, in upregulation and downregulation of Tensin 3. We conclude that in CRC, Cten is upregulated by EGFR and Kras but downregulated by STAT3. We show that calpain may be a negative regulator of Cten and that a Tensin switch does not occur and, if anything, Cten stabilizes Tensin 3.

Introduction The use of sunscreen is an important preventive measure against skin cancer and treatment for other skin conditions. There is evidence pointing to lack awareness and misconceptions regarding use of Sunscreen. This is especially evident in populations with skin of color (POC). Methods This is a cross‐sectional study of 2000 individuals. A structured questionnaire was designed to collect data on general knowledge and use of sunscreen as well as reasons for stopping use of sunscreen. Results The results of this study indicate a clear deficiency in the use and knowledge about sunscreen among Jordanians. Females are using sunscreen more than males. However, the use of sunscreen is inadequate in many aspects including timing of application, frequency of use, and amount used among other things. There is an obvious lack of knowledge about sunscreen as shown by lack of awareness about benefits of use in various times of the year, use in children, use for all skin types, and several misconceptions among other knowledge gaps. Main reasons for stopping sunscreen include side effects, cost, and being not suitable for skin. Awareness about sunscreen can be improved by proper counseling by healthcare professionals and utilization of various media platforms. Conclusions The use of sunscreen is inadequate in this population of color (POC). Lack of proper counseling, failure to read use instructions can contibute to inadequate use of sunscreen. Risks and benefits of sunscreen should be explained by medical professionals. The media should be more utilized to disseminate such knowledge.

BackgroundLittle is know about the outcomes of acute heart failure (AHF) with acute coronary syndrome (ACS-AHF), compared to those without ACS (NACS-AHF).MethodsWe conducted a prospective registry of AHF patients involving 18 hospitals in Saudi Arabia between October 2009 and December 2010. In this sub-study, we compared the clinical correlates, management and hospital course, as well as short, and long-term outcomes between AHF patients with and without ACS.ResultsOf the 2609 AHF patients enrolled, 27.8 % presented with ACS. Compared to NACS-AHF patients, ACS-AHF patients were more likely to be old males (Mean age = 62.7 vs. 60.8 years, p = 0.003, and 73.8 % vs. 62.7 %, p < 0.001, respectively), and to present with De-novo heart failure (56.6 % vs. 28.1 %, p < 0.001). Additionally they were more likely to have history of ischemic heart disease, diabetes, dyslipidemia, and less likely to have chronic kidney disease (p < 0.001 for all comparisons). The prevalence of severe LV systolic dysfunction (EF < 30 %) was higher in ACS-AHF patients. During hospital stay, ACS-AHF patients were more likely to develop shock (p < 0.001), recurrent heart failure (p = 0.02) and needed more mechanical ventilation (p < 0.001). β blockers and Angiotensin Converting Enzyme inhibitors were used more often in ACS-AHF patients (p = 0.001 and, p = 0.004 respectively). ACS- AHF patients underwent more coronary angiography and had higher prevalence of multi-vessel coronary artery disease (p < 0.001 for all comparisons). The unadjusted hospital and one-month mortality were higher in ACS-AHF patients (OR = 1.6 (1.2–2.2), p = 0.003 and 1.4 (1.0–1.9), p = 0.026 respectively). A significant interaction existed between the level of left ventricular ejection fraction and ACS-AHF status. After adjustment, ACS-AHF status was only significantly associated with hospital mortality (OR = 1.6 (1.1–2.4), p = 0.019). The three-years survival following hospital discharge was not different between the two groups.ConclusionAHF patients presenting with ACS had worse hospital prognosis, and an equivalent long-term survival compared to AHF patients without ACS. These findings underscore the importance of timely recognition and management of AHF patients with concomitant ACS given their distinct presentation and underlying pathophysiology compared to other AHF patients.

In real-world clinical practice, WHF during hospitalization for AHF is a strong predictor for short- and intermediate-term mortality, and a cause for longer hospital stays.

BackgroundDNA prediction of eye color represent one application of the externally visible characteristics (EVC), which attained growing interest in the field of DNA forensic phenotyping. This is mainly due to its ability to narrow the pool of suspects without the need to compare any retrieved DNA material from the crime scene to a reference DNA. Several methods and multiplex genetic panel were proposed with variable prediction accuracy between different populations. However, such panel was not previously tested in the Saudi population, nor any populations of the Middle East and North Africa origin.MethodA panel of eleven single nucleotide polymorphisms (SNPs) was tested for their association with three eye colors (brown, hazel, and intermediate) in 80 volunteer Saudi individuals. SNPs and haplotype association test with eye colors were performed to identify the top significant SNPs with the three eye colors. Also, multinomial logistic regression was used to construct the prediction model using a training set of 60 subjects, and a validation set of 20 subjects. The goodness of fit parameter of the model to correctly predicts each eye color as compared to the other was performed.ResultsEye color was significantly associated with rs12913832, rs7170852, and rs916977 that are located within HERC2. SNP rs12913832 was the top significant SNP (p-value = 1.78E−15) that accounted for the association in this region, as the other SNPs were not significant after adjusting for rs12913832. A prediction model containing five SNPs showed high prediction accuracy with Area Under the receiver operating characteristic Curves (AUC) equals to 0.95 and 0.83 for brown and intermediate eye colors, respectively. However, the model’s performance was very low for predicting the hazel eye color with AUC equals 0.75.DiscussionDespite the small sample size of our study, we reported very significant SNP associations with eye color. Our model to predict eye colors based on DNA material showed high accuracy for brown and intermediate eye colors. The eye color prediction-model underperformed for the hazel eye colors, suggesting that larger sample size, as well as more comprehensive set of SNPs, could improve the model-prediction accuracy.

B-cells of the high-grade non-Hodgkin lymphoma Burkitt's lymphoma (BL) overexpress survival oncoproteins, including the proviral integration site for Moloney murine leukaemia virus kinase (Pim)-1, and become apoptosis resistant. Activated death receptor CD95 after ligation with anti-CD95 monoclonal antibody (mAb) resulted in the regression of BL via induction of apoptosis, suggesting a decrease of survival protein expression. Here, CD95-mediated apoptotic pathways in BL B-cell lines (Raji and Daudi) following treatment with anti-CD95 mAb was investigated with the cause-and-effects on pim-1 gene expression, in comparison with leukemic cell line (K562) used as CD95-negative cells. Immunohistochemical staining for CD95 and Pim-1 was performed, and the effects of anti-CD95 mAb on apoptotic signalling using western blotting, on caspase activity and cell survival of BL B-cell and leukemic cell lines were determined. We showed that Raji cells expressed more CD95 receptors than Daudi cells. Half of each population underwent apoptosis accompanied by decreased cell viability after anti-CD95 mAb treatment. Distinct extrinsic and intrinsic CD95-mediated apoptotic pathways in Raji and Daudi cells were revealed by high caspase activity and mitochondrial outer membrane permeabilization, respectively. We observed decreased Pim-1 transcript and protein expression levels with increased heat-shock protein (Hsp)70 and decreased Hsp90 expression in anti-CD95 mAb-treated cells. Throughout the study, K562 cells did not undergo apoptosis upon anti-CD95 mAb treatment. Pim-1 knockdown following to stable transfection with plasmid vectors induced apoptosis and decreased viability of BL and K562 cells. Therefore, CD95-mediated apoptosis induces Pim-1 down-regulation in BL B-cells, but Pim-1 down-regulation cannot fully eradicate BL and leukaemia.

Coronary sinus (CS) anomalies such as diverticulum, persistent left superior vena cava or CS ostium dilatation are predominantly found in patients with accessory pathway-related tachycardias. Diverticulum of the proximal CS found in 7-11% of patients with postero-septal or left posterior manifests accessory pathways. We reported a 28 year old gentleman with manifested postero-septal accessory pathway, who underwent repeat electrophysiological study (EPS) and radiofrequency ablation for previously failed ablation. Huge CS diverticulum was identified by angiography as a reason for resistant accessory pathway. Successful RF ablation was achieved at the neck of the diverticulum without complications. Other associated anomalies were ruled out by cardiac computerized tomography (CT) and trans-esophageal echocardiography.