Effects of tamoxifen on normal breast tissue histological composition: Results from a randomised six-arm placebo-controlled trial in healthy women

Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk-reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double-blinded dose-determination trial KARISMA, investigated tamoxifen-specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to “no dose” (0-1 mg), “low-dose” (2.5-5 mg) or “high-dose” (10-20 mg) of tamoxifen. Ultrasound-guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end-of-tamoxifen-exposure. We found that different doses of tamoxifen reduced mammographic density and glandular-epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High-dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high-dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen.     

Family correlates of daughter's and son's locus of control expectancies during childhood

Children who expect they can bring about good outcomes and avoid bad outcomes tend to experience more personal successes. Little is known about factors that contribute to these ‘control expectancies’. The purpose of the present study was to determine whether children's internal control expectancies occur in the context of parents’ internal control expectancies, low family strain, and high family cohesiveness and whether these factors are more strongly related to daughters’ than sons’ control expectancies. A community sample of 85 children aged 9–11 years and their parents (85 mothers; 63 fathers) completed rating scales. Fathers’ more internal control expectancies and mothers’ reports of fewer family strains were associated with daughters’ but not sons’ greater internal control expectancies, and greater family cohesiveness was related to both daughters’ and sons’ internal control orientations. These findings suggest that family factors may contribute to children's, particularly daughters’, development of internal control expectancies.     

Defining metronidazole-induced encephalopathy

Journal of Neurology -     

Job hazards and respiratory symptoms in Hispanic female domestic cleaners

Abstract

The occupational hazards and respiratory symptoms of domestic cleaners in USA are largely unknown. We conducted a cross-sectional study among 56 Hispanic female domestic cleaner on their health status and frequency of cleaning products used and tasks performed. While women used multi-use products (60.0%) and toilet bowl cleaners (51.8%) most days of the week, many (39.3%) reported not using personal protective equipment while cleaning. Itchy/watery eyes (61.8%) and itchy nose (56.4%) were the most frequently reported symptoms. A history of physician-diagnosed asthma was reported by 14.3% while 33.9% had symptoms of bronchial hyperresponsiveness (BHR). In conclusion, this vulnerable population has high prevalence of physician-diagnosis asthma and BHR symptoms and is potentially exposed to myriad occupational hazards. Further research exploring associations between products use, cleaning tasks and respiratory symptoms is warranted.     

Dating, sexual activity, and well-being in Italian adolescents.

Associations among dating, sexual activity, gender, and adjustment were investigated in 2,273 Italian adolescents (54% female, ages 14 to 19 years) attending public high schools. After controlling for age and type of school attended, both being in a dating relationship and being male were associated with less alienation, more positive views of the self, and higher general expectations for success. Sexual activity interacted with both gender and dating status in predicting feelings of depression. For boys, there were no differences between youth who were sexually active and youth who were not; however, sexually active girls had higher levels of depressive symptoms than girls who were not sexually active. Among youth who were not sexually active, there were small differences between daters and nondaters; among sexually active youth, daters had lower levels of depression than nondaters. Gender differences in adolescents' experience of dating and sexual relationships and implications for adjustment are discussed.