BackgroundThe current conflict in Syria continues to displace thousands to neighboring countries, including Lebanon. Information is needed to provide adequate health and related services particularly to women in this displaced population.MethodsWe conducted a needs assessment in Lebanon (June-August 2012), administering a cross-sectional survey in six health clinics. Information was collected on reproductive and general health status, conflict violence, stress, and help-seeking behaviors of displaced Syrian women. Bivariate and multivariate analyses were conducted to examine associations between exposure to conflict violence, stress, and reproductive health outcomes.ResultsWe interviewed 452 Syrian refugee women ages 18–45 who had been in Lebanon for an average of 5.1 (± 3.7) months. Reported gynecologic conditions were common, including: menstrual irregularity, 53.5%; severe pelvic pain, 51.6%; and reproductive tract infections, 53.3%. Among the pregnancy subset (n = 74), 39.5% of currently pregnant women experienced complications and 36.8% of those who completed pregnancies experienced delivery/abortion complications. Adverse birth outcomes included: low birthweight, 10.5%; preterm delivery, 26.5%; and infant mortality, 2.9%. Of women who experienced conflict-related violence (30.8%) and non-partner sexual violence (3.1%), the majority did not seek medical care (64.6%). Conflict violence and stress score was significantly associated with reported gynecologic conditions, and stress score was found to mediate the relationship between exposure to conflict violence and self-rated health.ConclusionsThis study contributes to the understanding of experience of conflict violence among women, stress, and reproductive health needs. Findings demonstrate the need for better targeting of reproductive health services in refugee settings, as well as referral to psychosocial services for survivors of violence.

Treatment of A549 cells with C 6 -ceramide resulted in a significant increase in the endogenous long chain ceramide levels, which was inhibited by fumonisin B1 (FB1), and not by myriocin (MYR). The biochemical mechanisms of generation of endogenous ceramide were investigated using A549 cells treated with selectively labeled C 6 -ceramides, [sphingosine-3- The results demonstrated that 3 H label was incorporated into newly synthesized long chain ceramides, which was inhibited by FB1 and not by MYR. Interestingly, the 14 C label was not incorporated into long chain ceramides. Taken together, these results show that generation of endogenous ceramide in response to C 6 -ceramide is due to recycling of the sphingosine backbone of C 6 -ceramide via deacylation/ reacylation and not due to the elongation of its fatty acid moiety. Moreover, the generation of endogenous long chain ceramide in response to C 6 -ceramide was completely blocked by brefeldin A, which causes Golgi disassembly, suggesting a role for the Golgi in the metabolism of ceramide. In addition, the generation of endogenous ceramide in response to short chain exogenous ceramide was induced by D-erythro-but not L-erythro-C 6 -ceramide, demonstrating the stereospecificity of this process. Interestingly, several key downstream biological activities of ceramide, such as growth inhibition, cell cycle arrest, and modulation of telomerase activity were induced by D-erythro-C 6 -ceramide, and not L-erythro-C 6 -ceramide (and inhibited by FB1) in A549 cells, suggesting a role for endogenous long chain ceramide in the regulation of these responses.

In vertebrates, heart formation which integrates different structures and cell types is a complex process that involves a network of genes regulated by transcription factors. Proper spatiotemporal expression of these factors ensure the highly needed tight control of each step in organogenesis. A mistake at any step from cell-commitment to valve formation will have a major impact on heart morphogenesis and function leading to congenital heart disease (CHD). Cardiac abnormalities occur with an incidence of one per 100 live births and represent 25% of all congenital malformations. As an alternative approach to linkageanalysis of familial cases of CHD, we started screening familial and sporadic cases of CHDs in a highly consanguineous population for mutations in genes encoding cardiac-enriched transcription factors. The evolutionarily conserved role of these proteins in cardiac development suggested a role in CHD. In this study, we report a mutation in the gene encoding GATA4, one of the earliest markers of heart development. This mutation was found in two out of 26 patients with Tetralogy of Fallot (TOF), and in none of the 94 patients with different phenotypes included in the study, nor in 223 healthy individuals. The heterozygous mutation results in an amino acid substitution in the first zinc finger of GATA4 that reduced its transcriptional activation of downstream target genes, without affecting GATA4 ability to bind DNA, nor its interaction with ZFPM2.

We previously detected a membrane-bound, copper-containing oxidase that may be involved in iron efflux in BeWo cells, a human placental cell line. We have now identified a gene encoding a predicted multicopper ferroxidase (MCF) with a putative C-terminal membrane-spanning sequence and high sequence identity to hephaestin (Heph) and ceruloplasmin (Cp), the other known vertebrate MCF. Molecular modeling revealed conservation of all type I, II, and III copper-binding sites as well as a putative iron-binding site. Protein expression was observed in multiple diverse mouse tissues, including placenta and mammary gland, and the expression pattern was distinct from that of Cp and Heph. The protein possessed ferroxidase activity, and protein levels decreased in cellular copper deficiency. Knockdown with small interfering RNA in BeWo cells indicates that this gene represents the previously detected oxidase. We propose calling this new member of the MCF family "zyklopen."

This study was designed to analyze whether ceramide, a bioeffector of growth suppression, plays a role in the regulation of telomerase activity in A549 cells. Telomerase activity was inhibited significantly by exogenous C 6 -ceramide, but not by the biologically inactive analog dihydro-C 6 -ceramide, in a time-and dose-dependent manner, with 85% inhibition produced by 20 M showing that the increased endogenous ceramide is sufficient for telomerase inhibition. Moreover, treatment of A549 cells with daunorubicin at 1 M for 6 h resulted in the inhibition of telomerase, which correlated with the elevation of endogenous ceramide levels and growth arrest. Finally, stable overexpression of human glucosylceramide synthase, which attenuates ceramide levels by converting ceramide to glucosylceramide, prevented the inhibitory effects of C 6 -ceramide and daunorubicin on telomerase. Therefore, these results provide novel data showing for the first time that ceramide is a candidate upstream regulator of telomerase.