Distinct roles of estrone and estradiol in endothelial colony-forming cells.

Our current understanding of the relationship between estrogen and human endothelial colony-forming cell (hECFC) function is based almost exclusively on studies investigating estradiol action at nuclear estrogen receptors. In the current study the hypothesis was tested that the less potent estrogen receptor agonist, estrone, affects hECFC proliferation, migration, secretion, and tube formation in a way that is unique from that of estradiol. The relationship between the estrogens, estradiol and estrone, is clinically important, particularly in postmenopausal women where estradiol levels wane and estrone becomes the predominant estrogen. Cultured hECFCs from peripheral blood mononuclear cell fractions were treated with concentrations of estradiol and estrone ranging from 1 nM to 1 μM separately and in combination. Following treatment, proliferation, migration, ability to attract other hECFCs (autocrine secretion), and ability to enhance endothelial cell tube formation (tubulogenesis) were tested. Functional assays revealed unique, concentration-dependent physiological effects of estrone and estradiol. Estradiol exposure resulted in increased hECFC proliferation, migration, secretion of chemoattractant, and enhancement of tube formation as expected. As with estradiol, hECFC secretion of chemoattractant increased significantly with each increase in estrone exposure. Estrone treatment produced a biphasic, concentration-dependent relationship with proliferation and tube formation and relatively no effect on hECFC migration at any concentration. The quantitative relationship between the effects of estrone and estradiol and each hECFC function was analyzed. The extent to which estrone was similar in effect to that of estradiol was dependent on both the concentrations of estradiol and estrone and the hECFC function measured. Interestingly, when the two estrogens were present, differing ratios resulted in unique functional responses. hECFCs that were treated with combinations of estrone and estradiol with high estrone to estradiol ratios showed decreased proliferative capacity. Conversely, hECFCs that were treated with combinations that were relatively high in estradiol, showed increased proliferative capacity. Cells that were treated with estrone and estradiol in equal concentrations showed an attenuated proliferative response that was decreased compared to the proliferation that either estrone or estradiol produced when they were present alone. This co-inhibitory relationship, which has not been previously reported, challenges the prevailing understanding of estrone as solely a weak agonist at estrogen receptors. This study provides evidence that estrone signaling is distinct from that of estradiol and that further investigation of estrone\u27s mechanism of action and the biological effect may provide important insight into understanding the dysfunction and decreased number of hECFCs, and the resulting cardiovascular disease risk observed clinically in menopausal women and women undergoing hormone replacement therapy

The Big Five as Predictors of Behavioral Health Professional Burnout

While the majority of studies appeared to focus on health service workers and job satisfaction, there was a substantial lack of literature that explored the relationship of personality traits and burnout specific to behavioral health professionals. Research has indicated that behavioral health professional burnout is a mediating factor in early job exodus primarily due to highly interactive work with people. The purpose of this study was to consider the relationship between behavioral health professional burnout, as measured by the Maslach Burnout Inventory for Health and Human Service workers, and the big five personality traits, as measured by the NEO Five Factor Inventory. This multiple regression study evaluated 305 behavioral health professionals who were currently licensed and practicing in the Commonwealth of Kentucky and Ohio. Results of the study yielded a significant correlation between behavioral health professional burnout and personality traits. The more extraverted, open, agreeable, and conscientious behavioral health professionals are, the less likely they are to experience burnout. The more narcissistic behavioral health professionals are, the more likely they are to experience burnout. In addition, age significantly correlated to behavioral health professional burnout. As age increased, burnout potential decreased. The implications for social change include potential use at the organizational level to implement policy changes, such as regular or preburnout screenings, in order to prevent early exodus from the behavioral health field and increase positive patient outcomes

Options for basing Dietary Reference Intakes (DRIs) on chronic disease endpoints: report from a joint US-/Canadian-sponsored working group.

Dietary Reference Intakes (DRIs) are used in Canada and the United States in planning and assessing diets of apparently healthy individuals and population groups. The approaches used to establish DRIs on the basis of classical nutrient deficiencies and/or toxicities have worked well. However, it has proved to be more challenging to base DRI values on chronic disease endpoints; deviations from the traditional framework were often required, and in some cases, DRI values were not established for intakes that affected chronic disease outcomes despite evidence that supported a relation. The increasing proportions of elderly citizens, the growing prevalence of chronic diseases, and the persistently high prevalence of overweight and obesity, which predispose to chronic disease, highlight the importance of understanding the impact of nutrition on chronic disease prevention and control. A multidisciplinary working group sponsored by the Canadian and US government DRI steering committees met from November 2014 to April 2016 to identify options for addressing key scientific challenges encountered in the use of chronic disease endpoints to establish reference values. The working group focused on 3 key questions: 1) What are the important evidentiary challenges for selecting and using chronic disease endpoints in future DRI reviews, 2) what intake-response models can future DRI committees consider when using chronic disease endpoints, and 3) what are the arguments for and against continuing to include chronic disease endpoints in future DRI reviews? This report outlines the range of options identified by the working group for answering these key questions, as well as the strengths and weaknesses of each option

A lifespan study of the confidence-accuracy relation in working memory and episodic long-term memory

The relation between an individual’s memory accuracy and reported confidence in their memories can indicate self-awareness of memory strengths and weaknesses. We provide a lifespan perspective on this confidence-accuracy relation, based on two previously published experiments with 320 participants, including children aged 6 to 13, young adults aged 18 to 27, and older adults aged 65 to 77, across tests of working memory (WM) and long-term memory (LTM). Participants studied visual items in arrays of varying set sizes and completed item recognition tests featuring six-point confidence ratings either immediately after studying each array (WM tests) or following a long period of study events (LTM tests). Confidence-accuracy characteristic analyses showed that accuracy improved with increasing confidence for all age groups and in both WM and LTM tests. These findings reflect a universal ability across the lifespan to use awareness of the strengths and limitations of one’s memories to adjust reported confidence. Despite this age invariance in the confidence-accuracy relation, however, young children were more prone to high-confidence memory errors than other groups in tests of WM, whereas older adults were more susceptible to high-confidence false alarms in tests of LTM. Thus, although participants of all ages can assess when their memories are weaker or stronger, individuals with generally weaker memories are less adept at this confidence-accuracy calibration. Findings also speak to potential different sources of high-confidence memory errors for young children and older adults, relative to young adults

The proportion of working memory items recoverable from long-term memory remains fixed despite adult aging.

We explored whether long-term memory (LTM) retrieval is constrained by working memory (WM) limitations, in 80 younger and 80 older adults. Participants performed a WM task with images of unique everyday items, presented at varying set sizes. Subsequently, we tested participants’ LTM for items from the WM task and examined the ratio of LTM/WM retention. While older adults’ WM and LTM were generally poorer than that of younger adults, their LTM deficit was no greater than what was predicted from their WM performance. The ability to encode WM information into LTM appeared immune to age-related cognitive decline

Distance to the RR Lyrae Star V716 Monocerotis

We present high quality BVRI CCD photometry of the variable star V716 Monocerotis (= NSV 03775). We confirm it to be an RR Lyrae star of variability type ab (i.e. a fundamental mode pulsator), and determine its metallicity ([Fe/H] = -1.33 +/- 0.25), luminosity (Mv = 0.80 +/- 0.06), and foreground reddening (E(B-V) = 0.05-0.17) from the Fourier components of its light curve. These parameters indicate a distance of 4.1 +/- 0.3 kpc, placing V716 Mon near the plane of the Galaxy well outside the solar circle. This research was conducted as part of the 1999 Research Experiences for Undergraduates (REU) and Practicas de Investigacion en Astronomia (PIA) Programs at Cerro Tololo Inter-American Observatory (CTIO).Comment: 9 pages including 2 figures and 2 tables; accepted by PAS

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations