Validation of the French 3-year prognostic score using the Canadian Cystic Fibrosis registry

Studies of large CF populations using registry data are important to identify people at high risk for death. Nkam et al. published a prognostic score developed on French CF registry data to predict death or lung transplantation (LT) over a 3-year period in the adult CF population. The goal of our study was to validate the proposed tool using the Canadian CF registry. Using data between 2011 and 2014, a total of 2043 adult CF patients were included. We found that the French prognostic score was a good predictor of death or LT in the Canadian CF population (OR for each unit increase: 3.12, 95% CI: 2.74–3.55; p value < 0.001). The proposed prognostic score accurately categorizes patients when applied to an external dataset. This score provides an important tool for early identification of patients at high risk for death or LT, in whom specific therapeutic intervention can be proposed.     

Pax3 regulation of FGF signaling affects the progression of embryonic progenitor cells into the myogenic program

Pax3/7-dependent stem cells play an essential role in skeletal muscle development. We now show that Fgfr4 lies genetically downstream from Pax3 and is a direct target. In chromatin immunoprecipitation (ChIP)-on-chip experiments, Pax3 binds to a sequence 3' of the Fgfr4 gene that directs Pax3-dependent expression at sites of myogenesis in transgenic mouse embryos. The activity of this regulatory element is also partially dependent on E-boxes, targets of the myogenic regulatory factors, which are expressed as progenitor cells enter the myogenic program. Other FGF signaling components, notably Sprouty1, are also regulated by Pax3. In vivo manipulation of Sprouty expression reveals that FGF signaling affects the balance between Pax-positive progenitor cells and committed myoblasts. These results provide new insight into the Pax-initiated regulatory network that modulates stem cell maintenance versus tissue differentiation.     

Increased risk of gastric cancer in Japanese subjects is associated with microsatellite polymorphisms in the heme oxygenase-1 and the inducible nitric oxide synthase gene promoters

Microsatellite polymorphism in the promoter region of the heme oxygenase-1 (HO-1) gene was analyzed jointly with that of the inducible nitric oxide synthase (iNOS) gene among Japanese subjects (control and gastric cancer patients). A higher promoter activity genotype of the HO-1 gene was associated with increased risk for gastric cancer in women. Gastric cancer risk was notably increased in subjects carrying a higher promoter activity genotype for both HO-1 and iNOS compared to those with a lower promoter activity genotype for both genes. Our data suggest that genetic polymorphisms of HO-1 and iNOS modulate individual susceptibility to gastric cancer risk.     

Consumption of argan oil may have an antiatherogenic effect by improving paraoxonase activities and antioxidant status: Intervention study in healthy men

BACKGROUND AND AIM: Due to its high antioxidant and mono- and polyunsaturated fatty acid content virgin argan oil (VAO) could play a beneficial role in cardiovascular prevention. We were therefore interested in determining whether the consumption of VAO could improve plasma paraoxonase (PON1) activities and antioxidant status in healthy men. METHODS AND RESULTS: Sixty young men were included in this interventional study. They were given a controlled diet for 2 weeks as baseline and then received 25 g/day of butter. The group was randomised to two diet group periods of 3 weeks each. The VAO group received 25 ml/day of oil and the extra virgin olive oil (EVO) group received the same quantity of EVO as control group. Plasma PON1 activities, antioxidant vitamins and LDL susceptibility to oxidation were measured. The analysis of the results shows that PON1 activities increase significantly in both groups and that lipoperoxides and conjugated dienes formation decreases significantly in VAO and EVO groups compared to baseline values (P=0.001 and P=0.014, respectively). Vitamin E concentration increases significantly only in VAO group (P=0.007). Susceptibility of LDL to lipid peroxidation shows a significant increase in lag phase and a significant decrease in maximum diene production in VAO (P=0.005) and EVO groups (P=0.041 and P=0.005, respectively). CONCLUSIONS: Our findings confirm the beneficial effect of EVO on plasma antioxidant status and show for the first time the same effect for VAO supplementation in man. Thus, VAO offers an additional natural food supplement to reduce cardiovascular risk.     

EB-D fibronectin expression in squamous cell carcinoma of the head and neck

ED-B fibronectin (ED-B FN), a glycoprotein involved in cell adhesion and migration, is expressed in fetal and neoplastic tissues and absent in their normal counterparts. The aim of this study is to evaluate the expression of this glycoprotein in relation to the histological and clinical data and to determine whether it has a prognostic value in patients with head and neck squamous cell carcinoma (HNSCC). Ninety-five cases were assessed for ED-B FN expression using immunohistochemistry. Positive ED-B FN expression was significantly associated with tumor grade (p=0.06) and primary tumor site (p=0.02). The larynx was the tumor site associated with the least ED-B FN expression. In univariate analysis, there was no association with disease-free survival (p=0.48), but the mean time to progression was clearly shorter in tumors with positive ED-B FN expression than in those with negative expression (6 vs. 11 months). Patients having tumors expressing the ED-B FN had a trend to a significant lower overall survival in the multivariate analysis (p=0.06). Our study showed that ED-B FN expression might have a prognostic value in patients with HNSCC.