Men perform comparably to women in a perspective taking task after administration of intranasal oxytocin but not after placebo

Oxytocin (OT) is thought to play an important role in human interpersonal information processing and behavior. By inference, OT should facilitate empathic responding, i.e. the ability to feel for others and to take their perspective. In two independent double-blind, placebo-controlled between-subjects studies, we assessed the effect of intranasally administered OT on affective empathy and perspective taking, whilst also examining potential sex differences (e.g., women being more empathic than men). In study 1, we provided 96 participants (48 men) with an empathy scenario and recorded self reports of empathic reactions to the scenario, while in study 2, a sample of 120 individuals (60 men) performed a computerized implicit perspective taking task. Whilst results from Study 1 showed no influence of OT on affective empathy, we found in Study 2 that OT exerted an effect on perspective taking ability in men. More specifically, men responded faster than women in the placebo group but they responded as slowly as women in the OT group. We conjecture that men in the OT group adopted a social perspective taking strategy, such as did women in both groups, but not men in the placebo group. On the basis of results across both studies, we suggest that self-report measures (such as used in Study 1) might be less sensitive to OT effects than more implicit measures of empathy such as that used in Study 2. If these assumptions are confirmed, one could infer that OT effects on empathic responses are more pronounced in men than women, and that any such effect is best studied using more implicit measures of empathy rather than explicit self-report measures.

Characterization of a genomic signature of pregnancy identified in the breast.

The objective of this study was to comprehensively compare the genomic profiles in the breast of parous and nulliparous postmenopausal women to identify genes that permanently change their expression following pregnancy. The study was designed as a two-phase approach. In the discovery phase, we compared breast genomic profiles of 37 parous with 18 nulliparous postmenopausal women. In the validation phase, confirmation of the genomic patterns observed in the discovery phase was sought in an independent set of 30 parous and 22 nulliparous postmenopausal women. RNA was hybridized to Affymetrix HG_U133 Plus 2.0 oligonucleotide arrays containing probes to 54,675 transcripts, scanned and the images analyzed using Affymetrix GCOS software. Surrogate variable analysis, logistic regression, and significance analysis of microarrays were used to identify statistically significant differences in expression of genes. The false discovery rate (FDR) approach was used to control for multiple comparisons. We found that 208 genes (305 probe sets) were differentially expressed between parous and nulliparous women in both discovery and validation phases of the study at an FDR of 10% and with at least a 1.25-fold change. These genes are involved in regulation of transcription, centrosome organization, RNA splicing, cell-cycle control, adhesion, and differentiation. The results provide initial evidence that full-term pregnancy induces long-term genomic changes in the breast. The genomic signature of pregnancy could be used as an intermediate marker to assess potential chemopreventive interventions with hormones mimicking the effects of pregnancy for prevention of breast cancer.

Device-specific weighted T-score for two quantitative ultrasounds: operational propositions for the management of osteoporosis for 65 years and older women in Switzerland.

The World Health Organization (WHO) criteria for the diagnosis of osteoporosis are mainly applicable for dual X-ray absorptiometry (DXA) measurements at the spine and hip levels. There is a growing demand for cheaper devices, free of ionizing radiation such as promising quantitative ultrasound (QUS). In common with many other countries, QUS measurements are increasingly used in Switzerland without adequate clinical guidelines. The T-score approach developed for DXA cannot be applied to QUS, although well-conducted prospective studies have shown that ultrasound could be a valuable predictor of fracture risk. As a consequence, an expert committee named the Swiss Quality Assurance Project (SQAP, for which the main mission is the establishment of quality assurance procedures for DXA and QUS in Switzerland) was mandated by the Swiss Association Against Osteoporosis (ASCO) in 2000 to propose operational clinical recommendations for the use of QUS in the management of osteoporosis for two QUS devices sold in Switzerland. Device-specific weighted "T-score" based on the risk of osteoporotic hip fractures as well as on the prediction of DXA osteoporosis at the hip, according to the WHO definition of osteoporosis, were calculated for the Achilles (Lunar, General Electric, Madison, Wis.) and Sahara (Hologic, Waltham, Mass.) ultrasound devices. Several studies (totaling a few thousand subjects) were used to calculate age-adjusted odd ratios (OR) and area under the receiver operating curve (AUC) for the prediction of osteoporotic fracture (taking into account a weighting score depending on the design of the study involved in the calculation). The ORs were 2.4 (1.9-3.2) and AUC 0.72 (0.66-0.77), respectively, for the Achilles, and 2.3 (1.7-3.1) and 0.75 (0.68-0.82), respectively, for the Sahara device. To translate risk estimates into thresholds for clinical application, 90% sensitivity was used to define low fracture and low osteoporosis risk, and a specificity of 80% was used to define subjects as being at high risk of fracture or having osteoporosis at the hip. From the combination of the fracture model with the hip DXA osteoporotic model, we found a T-score threshold of -1.2 and -2.5 for the stiffness (Achilles) determining, respectively, the low- and high-risk subjects. Similarly, we found a T-score at -1.0 and -2.2 for the QUI index (Sahara). Then a screening strategy combining QUS, DXA, and clinical factors for the identification of women needing treatment was proposed. The application of this approach will help to minimize the inappropriate use of QUS from which the whole field currently suffers.

Trends in lung cancer among young European women: the rising epidemic in France and Spain.

Lung cancer mortality in young women in the European Union (EU) has steadily increased until the mid 1990 s and has levelled off thereafter, but trends have been heterogeneous in various countries. We analyzed therefore age-standardized trends in lung cancer mortality in young women (20-44) for the 6 major European countries, using joinpoint regression. In the early 1970s the highest lung cancer mortality in young women was in the UK (2.1/100,000). UK rates, however, steadily declined and in 2000-2004 they were the lowest of all 6 major EU countries (1.2/100,000). The second lowest rate in 2000-2002 was in Italy, whose rates remained around 1.1/100,000 between 1970 and 1994, and increased to 1.4 thereafter. In Germany and Poland, lung cancer rates in young women rose from 0.8-1.0/100,000 in the early 1970s to 1.7-1.9 in the mid 1990 s and levelled off during the last decade. Major rises over recent years were observed in France (from 0.8/100,000 in 1985-1989 to 2.2 in 2000-2003) and in Spain (from 0.8 in the 1985-1989 to 1.7 in 2000-2004). Thus, France showed both the highest rate observed over the last 3 decades and the largest rise over the last 2 decades. Since recent trends in the young give relevant information to the likely future trends in middle age, the female lung cancer epidemic is likely to expand in southern Europe from the current rates of 5.0/100,000 in Spain and 7.7 in France to approach 20/100,000 within the next 2-3 decades. Urgent interventions for smoking cessation in women are therefore required.

Pregnancy-induced chromatin remodeling in the breast of postmenopausal women.

Early pregnancy and multiparity are known to reduce the risk of women to develop breast cancer at menopause. Based on the knowledge that the differentiation of the breast induced by the hormones of pregnancy plays a major role in this protection, this work was performed with the purpose of identifying what differentiation-associated molecular changes persist in the breast until menopause. Core needle biopsies (CNB) obtained from the breast of 42 nulliparous (NP) and 71 parous (P) postmenopausal women were analyzed in morphology, immunocytochemistry and gene expression. Whereas in the NP breast, nuclei of epithelial cells were large and euchromatic, in the P breast they were small and hyperchromatic, showing strong methylation of histone 3 at lysine 9 and 27. Transcriptomic analysis performed using Affymetrix HG_U133 oligonucleotide arrays revealed that in CNB of the P breast, there were 267 upregulated probesets that comprised genes controlling chromatin organization, transcription regulation, splicing machinery, mRNA processing and noncoding elements including XIST. We concluded that the differentiation process induced by pregnancy is centered in chromatin remodeling and in the mRNA processing reactome, both of which emerge as important regulatory pathways. These are indicative of a safeguard step that maintains the fidelity of the transcription process, becoming the ultimate mechanism mediating the protection of the breast conferred by full-term pregnancy.