Identification of novel variant, 1484delG in the 3'UTR of H3F3B, a member of the histone 3B replacement family, in ovarian tumors

Previous studies have implicated the chromosomal region at 17q25 as harboring tumor suppressor genes based on the frequent loss of heterozygosity (LOH) observed in epithelial ovarian cancers (EOC). RT-PCR validation of Affymetrix GeneChip expression of H3F3B, a member of the 3B histone family that maps to 17q25.1, revealed a doublet band in cDNA from one of four EOC cell lines, OV90. In contrast to three other EOC cell lines (TOV81D, TOV112D and TOV21G) and primary cultures derived from normal ovarian surface epithelial cells (NOSE), sequence analysis of the cDNA revealed a deletion of G at position 1484 of the transcribed sequence which is located within the 3'UTR of H3F3B. OV90 was derived from ascites fluid of an undifferentiated adenocarcinoma of ovarian origin. The variant allele was identified in 1 of 65 (2%) healthy women with no prior history of cancer and in 5 participants with ovarian tumors comprising of 4 of 79 (5%) malignant EOC, none of 10 low malignancy potential tumors, and 1 of 8 (13%) benign tumors. All carriers of the variant alleles were heterozygous and tumor samples did not exhibit preferential LOH of the normal allele. The variant allele was identified in EOC samples of clear cell (1 of 20), mucinous (1 of 8), mixed cell (1 of 3) and undifferentiated (1 of 2) histopathological subtypes but none of 34 serous or 12 endometrioid subtype tumors. One of 3 mucinous benign tumors also harbored the variant allele. The functional significance of the variant is unknown, however its presence in rare subtypes of ovarian epithelial tumors warrants further investigation.     

Incremental Costs in Giant Cell Arteritis

Objective

To assess and compare direct costs between giant cell arteritis (GCA) patients and matched controls and to identify incremental cost drivers.

Methods

We carried out a population‐based, retrospective cohort study using the French National Health Insurance System database. Cost analysis was performed from the French health insurance perspective and took into account direct medical and nonmedical costs (2014, €). Costs were evaluated according to different cost components and divided into periods of 6 months for the accurate assessment of care consumption. Longitudinal multivariate regression analyses using generalized estimating equations were used to adjust the effect of GCA on the mean cost over time.

Results

Analyses were performed on 96 incident GCA patients and 563 matched controls. The cumulative incremental cost due to GCA was €6,406 and €7,236 for 3 and 5 years, respectively. Total incremental costs were significant for the first 18 months, amounting to €1,342 for the first 6 months, €1,498 between 6 and 12 months, and €1,165 between 12 and 18 months (P = 0.012, P = 0.065, and P = 0.029, respectively). The most important cost drivers were paramedical procedures, inpatient stays, medication, and medical procedures. Multivariate analysis shows the significant effect of GCA on mean cost during the first 3 years of followup (relative risk [RR] 1.72 [95% confidence interval (95% CI) 1.31–2.27], P < 0.001) with significant cost reductions (RR 0.70 [95% CI 0.49–0.99], P = 0.05) at the end of followup.

Conclusion

This study provides an accurate assessment of GCA costs during a 5‐year period and gives useful information for future cost‐effectiveness studies based on new expensive biotherapies.

     

beta-adrenergic relaxation in pulmonary arteries: preservation of the endothelial nitric oxide-dependent beta2 component in pulmonary hypertension

AIMS: beta-adrenoceptor (beta-AR)-mediated relaxation was characterized in pulmonary arteries from normoxic and hypoxic (as model of pulmonary hypertension) mice. The endothelial NO synthase (eNOS) pathway was especially investigated because of its potential vasculoprotective effects. METHODS: Pulmonary arteries from control or hypoxic (0.5 atm for 21 days) wild-type or eNOS-/- mice were used for pharmacological characterization of beta-AR-mediated relaxation in myograph, and for immunohistochemistry using anti-beta-AR antibodies. RESULTS: In pulmonary arteries from normoxic mice, isoproterenol (beta-AR agonist) and procaterol (selective beta2-AR agonist) elicited relaxation, while cyanopindolol and CL316243 (beta3-AR agonists) were ineffective. The effect of isoproterenol was antagonized by CGP20712A and ICI118551 (beta1- or beta2-AR antagonists, respectively) and also partially inhibited by N omega-nitro-L-arginine methylester (L-NAME, a NOS inhibitor), endothelium denudation, or eNOS gene deletion. Relaxation to procaterol was abolished by L-NAME or endothelium removal. In eNOS-/- mice, procaterol-induced relaxation was decreased but was insensitive to L-NAME, this residual effect involving other endothelium-dependent relaxant factors as compensatory mechanisms. Immunostaining for beta2-AR was observed in the endothelial layer, but not the medial layer of pulmonary arteries. Pulmonary arteries from hypoxic mice exhibited decreased endothelial NO-dependent relaxation to acetylcholine. However, in these arteries, relaxation to procaterol was either unaffected (extralobar segments) or even increased (intralobar segments) and was still abolished by L-NAME or endothelium removal. CONCLUSION: beta1- and beta2-AR, but not beta3-AR, mediate relaxation of mice pulmonary arteries. The beta2-AR component is dependent on eNOS activity and is preserved following chronic hypoxia. These data highlight the role of the beta2-AR as a pharmacological target to induce/restore endothelial NO-dependent protective effects in pulmonary circulation.     

Selling Dreams: An Overview of Slimming Products’ Advertisements in Switzerland

ObjectiveThe aim of this work was to assess weight loss claims of slimming products available in Switzerland.MethodBetween May 2008 and February 2013, 31 advertisements for 13 slimming products were analyzed.ResultsTotal daily weight loss claims ranged between 300 g and 1 kg. 84% of the advertisements included the photograph of a woman, 61% showed a picture of a person before and after using the product, and 51% claimed that the product had improved marital relationships. The terms ‘natural’, ‘miracle/extraordinary’ and ‘scientific’ were present in 92%, 77% and 31% of the advertisements, respectively. Cost for one package of the product ranged between CHF 49.00 and 59.00 (USD 52.00 and 63.00), and no correlation was found between cost and weight loss claims. No differences were found for weight loss claims according to presence or absence of a picture or of the terms ‘natural’, ‘miracle/extraordinary’, and ‘scientific’. Assuming that 5.3% of readers bought the product, yearly revenues would range between CHF 12.5 and 33.8 million (USD 13.4 and 36.2 million).ConclusionsIn Switzerland, advertisements for slimming products use positive and reassuring terms to attract consumers, which are lured by unreachable, false promises of rapid and easy weight loss.Key Words: Obesity management, Public policy, Social determinants, Weight loss, Economics