Two-week dietary soy supplementation has an estrogenic effect on normal premenopausal breast.

An association has been reported between consumption of a high soy diet and a low incidence of breast cancer within populations of Southeast Asia. Phytoestrogens present in soy act as partial estrogen agonists or antagonists and can inhibit breast cancer cell proliferation in vitro. The effect of 14-day dietary soy supplementation with 60 g (45 mg isoflavones) on the normal breast of 84 premenopausal patients was determined. Serum concentrations of the isoflavanoids, genistein, daidzein, and equol, were raised in patients after soy supplementation (P < or = 0.025). Nipple aspirate (NA) levels of genistein and daidzein were higher than paired serum levels, both before (P < 0.001 and P = 0.001, respectively) and after soy supplementation (P < 0.001 and P = 0.049, respectively); however, there was no significant increase in NA isoflavone levels in response to soy. NA levels of apolipoprotein D were significantly lowered and pS2 levels raised in response to soy supplementation (P < or = 0.002), indicative of an estrogenic stimulus. No effect of soy supplementation on breast epithelial cell proliferation, estrogen and progesterone receptor status, apoptosis, mitosis, or Bcl-2 expression was detected. In conclusion, short term dietary soy has a weak estrogenic response on the breast, as measured by nipple aspirate apolipoprotein D and pS2 expression. No antiestrogenic effect of soy on the breast was detected

The clinical role of circulating free tumor DNA in gastrointestinal malignancy

Circulating cell-free DNA (cfDNA) is DNA released from necrotic or apoptotic cells into the bloodstream. While both healthy cells and cancer cells release cfDNA, tumors are associated with higher levels of tumor-derived circulating cell-free DNA (ctDNA) detectable in blood. Absolute levels of ctDNA and its genetic mutations and epigenetic changes show promise as potentially useful biomarkers of tumor biology, progression, and response to therapy. Moreover, studies have demonstrated the discriminative accuracy of ctDNA levels for diagnosis of gastrointestinal cancer compared with benign inflammatory diseases. Therefore, ctDNA detected in blood offers a minimally invasive and easily repeated “liquid biopsy” of cancer, facilitating real-time dynamic analysis of tumor behavior that could revolutionize both clinical and research practices in oncology. In this review, we provide a critical summary of the evidence for the utility of ctDNA as a diagnostic and prognostic biomarker in gastrointestinal malignancies

Depleted circulatory complement-lysis inhibitor (CLI) in childhood cerebral malaria returns to normal with convalescence

BACKGROUND: Cerebral malaria (CM), is a life-threatening childhood malaria syndrome with high mortality. CM is associated with impaired consciousness and neurological damage. It is not fully understood, as yet, why some children develop CM. Presented here is an observation from longitudinal studies on CM in a paediatric cohort of children from a large, densely-populated and malaria holoendemic, sub-Saharan, West African metropolis. METHODS: Plasma samples were collected from a cohort of children with CM, severe malarial anaemia (SMA), uncomplicated malaria (UM), non-malaria positive healthy community controls (CC), and coma and anemic patients without malaria, as disease controls (DC). Proteomic two-dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry were used in a discovery cohort to identify plasma proteins that might be discriminatory among these clinical groups. The circulatory levels of identified proteins of interest were quantified by ELISA in a prospective validation cohort. RESULTS: The proteome analysis revealed differential abundance of circulatory complement-lysis inhibitor (CLI), also known as Clusterin (CLU). CLI circulatory level was low at hospital admission in all children presenting with CM and recovered to normal level during convalescence (p < 0.0001). At acute onset, circulatory level of CLI in the CM group significantly discriminates CM from the UM, SMA, DC and CC groups. CONCLUSIONS: The CLI circulatory level is low in all patients in the CM group at admission, but recovers through convalescence. The level of CLI at acute onset may be a specific discriminatory marker of CM. This work suggests that CLI may play a role in the pathophysiology of CM and may be useful in the diagnosis and follow-up of children presenting with CM

Relationships between CYP2D6 phenotype, breast cancer and hot flushes in women at high risk of breast cancer receiving prophylactic tamoxifen: results from the IBIS-I trial

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An Inhibitory Antibody Blocks Interactions between Components of the Malarial Invasion Machinery

Host cell invasion by apicomplexan pathogens such as the malaria parasite Plasmodium spp. and Toxoplasma gondii involves discharge of proteins from secretory organelles called micronemes and rhoptries. In Toxoplasma a protein complex comprising the microneme apical membrane antigen 1 (AMA1), two rhoptry neck proteins, and a protein called Ts4705, localises to the moving junction, a region of close apposition between parasite and host cell during invasion. Antibodies against AMA1 prevent invasion and are protective in vivo, and so AMA1 is of widespread interest as a malaria vaccine candidate. Here we report that the AMA1 complex identified in Toxoplasma is conserved in Plasmodium falciparum. We demonstrate that the invasion-inhibitory monoclonal antibody (mAb) 4G2, which recognises P. falciparum AMA1 (PfAMA1), cannot bind when PfAMA1 is in a complex with its partner proteins. We further show that a single completely conserved PfAMA1 residue, Tyr251, lying within a conserved hydrophobic groove adjacent to the mAb 4G2 epitope, is required for complex formation. We propose that mAb 4G2 inhibits invasion by preventing PfAMA1 from interacting with other components of the invasion complex. Our findings should aid the rational design of subunit malaria vaccines based on PfAMA1

Things change: Women’s and men’s marital disruption dynamics in Italy during a time of social transformations, 1970-2003

We study women’s and men’s marital disruption in Italy between 1970 and 2003. By applying an event-history analysis to the 2003 Italian variant of the Generations and Gender Survey we found that the spread of marital disruption started among middle-highly educated women. Then in recent years it appears that less educated women have also been able to dissolve their unhappy unions. Overall we can see the beginning of a reversed educational gradient from positive to negative. In contrast the trend in men’s marital disruption risk appears as a change over time common to all educational groups, although with persisting educational differentials.determinants, educational differences, event history analysis, gender difference, Italy, marital disruption

Intermediate Outcomes, Strategies, and Challenges of Eight Healthy Start Projects

Site visits were conducted for the evaluation of the national Healthy Start program to gain an understanding of how projects design and implement five service components (outreach, case management, health education, depression screening and interconceptional care) and four system components (consortium, coordination/collaboration, local health system action plan and sustainability) as well as program staff’s perceptions of these components’ influence on intermediate outcomes. Interviews with project directors, case managers, local evaluators, clinicians, consortium members, outreach/lay workers and other stakeholders were conducted during 3-day in-depth site visits with eight Healthy Start grantees. Grantees reported that both services and systems components were related to self-reported service achievements (e.g. earlier entry into prenatal care) and systems achievements (e.g. consumer involvement). Outreach, case management, and health education were perceived as the service components that contributed most to their achievements while consortia was perceived as the most influential systems component in reaching their goals. Furthermore, cultural competence and community voice were overarching project components that addressed racial/ethnic disparities. Finally, there was great variability across sites regarding the challenges they faced, with poor service availability and limited funding the two most frequently reported. Service provision and systems development are both critical for successful Healthy Start projects to achieve intermediate program outcomes. Unique contextual and community issues influence Healthy Start project design, implementation and reported accomplishments. All eight projects implement the required program components yet outreach, case management, and health education are cited most frequently for contributing to their perceived achievements

Type Ia Supernovae as Stellar Endpoints and Cosmological Tools

Empirically, Type Ia supernovae are the most useful, precise, and mature tools for determining astronomical distances. Acting as calibrated candles they revealed the presence of dark energy and are being used to measure its properties. However, the nature of the SN Ia explosion, and the progenitors involved, have remained elusive, even after seven decades of research. But now new large surveys are bringing about a paradigm shift --- we can finally compare samples of hundreds of supernovae to isolate critical variables. As a result of this, and advances in modeling, breakthroughs in understanding all aspects of SNe Ia are finally starting to happen.Comment: Invited review for Nature Communications. Final published version. Shortened, update

A phase I trial to assess the pharmacology of the new oestrogen receptor antagonist fulvestrant on the endometrium in healthy postmenopausal volunteers

While tamoxifen use is associated with clear benefits in the treatment of hormone-sensitive breast cancer, it also exhibits partial oestrogen agonist activity that is associated with adverse events, including endometrial cancer. Fulvestrant (‘Faslodex’) is a new oestrogen receptor antagonist that downregulates the oestrogen receptor and has no known agonist effect. This single-centre, double-blind, randomised, parallel-group trial was conducted to determine the direct effects of fulvestrant on the female endometrium when given alone and in combination with the oestrogen, ethinyloestradiol. Following a 14-day, pretrial screening period, 30 eligible postmenopausal volunteers were randomised to receive fulvestrant 250 mg, fulvestrant 125 mg or matched placebo administered as a single intramuscular injection. Two weeks postinjection, volunteers received 2-weeks concurrent exposure to ethinyloestradiol 20 μg day−1. Endometrial thickness was measured before and after the 14-day screening period with further measurements predose (to confirm a return to baseline) and on days 14, 28 and 42 post-treatment with fulvestrant. Pharmacokinetic and safety assessments were performed throughout the trial. Fulvestrant at a dose of 250 mg significantly (P=0.0001) inhibited the oestrogen-stimulated thickening of the endometrium compared with placebo. Neither the 125 mg nor 250 mg doses of fulvestrant demonstrated oestrogenic effects on the endometrium over the initial 14-day assessment period. Fulvestrant was well tolerated and reduced the incidence of ethinyloestradiol-related side effects. At the same dose level that is being evaluated in clinical trials of postmenopausal women with advanced breast cancer, fulvestrant (250 mg) is an antioestrogen with no evidence of agonist activity in the endometrium of healthy postmenopausal women

The feasibility and utility of grocery receipt analyses for dietary assessment

OBJECTIVE: To establish the feasibility and utility of a simple data collection methodology for dietary assessment. DESIGN: Using a cross-sectional design, trained data collectors approached adults (~20 – 40 years of age) at local grocery stores and asked whether they would volunteer their grocery receipts and answer a few questions for a small stipend ($1). METHODS: The grocery data were divided into 3 categories: "fats, oils, and sweets," "processed foods," and "low-fat/low-calorie substitutions" as a percentage of the total food purchase price. The questions assessed the shopper's general eating habits (eg, fast-food consumption) and a few demographic characteristics and health aspects (eg, perception of body size). Statistical Analyses Performed. Descriptive and analytic analyses using non-parametric tests were conducted in SAS. RESULTS: Forty-eight receipts and questionnaires were collected. Nearly every respondent reported eating fast food at least once per month; 27% ate out once or twice a day. Frequency of fast-food consumption was positively related to perceived body size of the respondent (p = 0.02). Overall, 30% of the food purchase price was for fats, oils, sweets, 10% was for processed foods, and almost 6% was for low-fat/low-calorie substitutions. Households where no one was perceived to be overweight spent a smaller proportion of their food budget on fats, oils, and sweets than did households where at least one person was perceived to be overweight (p = 0.10); household where the spouse was not perceived to be overweight spent less on fats, oils, and sweets (p = 0.02) and more on low-fat/low-calorie substitutions (p = 0.09) than did households where the spouse was perceived to be overweight; and, respondents who perceived themselves to be overweight spent more on processed foods than did respondents who did not perceive themselves to be overweight (p = 0.06). CONCLUSION: This simple dietary assessment method, although global in nature, may be a useful indicator of dietary practices as evidenced by its association with perceived weight status