Temporal records of diet diversity dynamics in individual adult female Steller sea lion (Eumetopias jubatus) vibrissae.

Detailed information on the nutrition of free-ranging mammals contributes to the understanding of life history requirements, yet is often quite limited temporally for most species. Reliable dietary inferences can be made by analyzing the stable carbon (C) and nitrogen (N) isotopic values (δ13C and δ15N) of some consumer tissues; exactly which tissue is utilized dictates the inferential scope. Steller sea lion (SSL) vibrissae are grown continuously without shedding and thus provide a continuous multi-year record of dietary consumption. We applied a novel kernel density approach to compare the δ13C and δ15N values along the length of SSL vibrissae with δ13C and δ15N distributions of potential prey species. This resulted in time-series of proportion estimates of dietary consumption for individual SSL. Substantial overlap in δ13C and δ15N distributions for prey species prevented a discrete species-scale assessment of SSL diets; however, a post hoc correlational analysis of diet proportion estimates revealed grouping by trophic level. Our findings suggest that adult female SSL diets in the western and central Aleutian Islands shift significantly according to season: diets contain a higher proportion of lower trophic level species (Pacific Ocean perch, northern rockfish, Atka mackerel and walleye pollock) in the summer, whereas in the winter SSL consume a much more diverse diet which includes a greater proportion of higher trophic level species (arrowtooth flounder, Kamchatka flounder, darkfin sculpin, Pacific cod, Pacific octopus, rock sole, snailfish, and yellow Irish lord).

Breastmilk from obese mothers has pro-inflammatory properties and decreased neuroprotective factors.

OBJECTIVE: To determine the impact of maternal obesity on breastmilk composition. STUDY DESIGN: Breastmilk and food records from 21 lean and 21 obese women who delivered full-term infants were analyzed at 2 months post-partum. Infant growth and adiposity were measured at birth and 2 months of age. RESULT: Breastmilk from obese mothers had higher omega-6 to omega-3 fatty acid ratio and lower concentrations of docosahexaenoic acid, eicosapentaenoic acid, docasapentaenoic acid and lutein compared with lean mothers (P<0.05), which were strongly associated with maternal body mass index. Breastmilk saturated fatty acid and monounsaturated fatty acid concentrations were positively associated with maternal dietary inflammation, as measured by dietary inflammatory index. There were no differences in infant growth measurements. CONCLUSION: Breastmilk from obese mothers has a pro-inflammatory fatty acid profile and decreased concentrations of fatty acids and carotenoids that have been shown to have a critical role in early visual and neurodevelopment. Studies are needed to determine the link between these early-life influences and subsequent cardiometabolic and neurodevelopmental outcomes.

The role of Tcfap2c in tumorigenesis and cancer growth in an activated Neu model of mammary carcinogenesis.

TFAP2C/AP-2γ influences development of the mammary gland and regulates patterns of gene expression in luminal and HER2-amplified breast cancer. The roles of TFAP2C in mammary gland tumorigenesis and in pathways critical to cancer progression remain poorly understood. To gain greater insight into oncogenic mechanisms regulated by TFAP2C, we examined mammary tumorigenesis in MMTV-Neu transgenic female mice with or without conditional knockout (KO) of Tcfap2c, the mouse homolog of TFAP2C. Loss of Tcfap2c increased the latency of tumorigenesis and tumors that formed demonstrated reduced proliferative index and increased apoptosis. In addition, tumors formed in Tcfap2c KO animals had a significant reduction in Egfr levels without a change in the expression of the Neu oncogene. The MMneu-flAP2C cell line was established from tumor tissue derived from MMTV-Neu/Tcfap2c(L/L) control animals and parallel cell lines with and without expression of Tcfap2c were created by transduction with adenovirus-empty and adenovirus-Cre, respectively. KO of Tcfap2c in vitro reduced activated phosphorylated-Erk, decreased cell viability, repressed tumor growth and was associated with attenuation of Egfr expression. Chromatin immunoprecipitation and direct sequencing and expression analysis confirmed that Egfr was a Tcfap2c target gene in murine, as well as human, mammary carcinoma cells. Furthermore, decreased viability of mammary cancer cells was directly related to Egfr functional blockade. We conclude that TFAP2C regulates tumorigenesis, cell growth and survival in HER2-amplified breast cancer through transcriptional regulation of EGFR. The findings have important implications for targeting the EGFR pathway in breast cancer.

TFAP2C governs the luminal epithelial phenotype in mammary development and carcinogenesis.

Molecular subtypes of breast cancer are characterized by distinct patterns of gene expression that are predictive of outcome and response to therapy. The luminal breast cancer subtypes are defined by the expression of estrogen receptor-alpha (ERα)-associated genes, many of which are directly responsive to the transcription factor activator protein 2C (TFAP2C). TFAP2C participates in a gene regulatory network controlling cell growth and differentiation during ectodermal development and regulating ESR1/ERα and other luminal cell-associated genes in breast cancer. TFAP2C has been established as a prognostic factor in human breast cancer, however, its role in the establishment and maintenance of the luminal cell phenotype during carcinogenesis and mammary gland development have remained elusive. Herein, we demonstrate a critical role for TFAP2C in maintaining the luminal phenotype in human breast cancer and in influencing the luminal cell phenotype during normal mammary development. Knockdown of TFAP2C in luminal breast carcinoma cells induced epithelial-mesenchymal transition with morphological and phenotypic changes characterized by a loss of luminal-associated gene expression and a concomitant gain of basal-associated gene expression. Conditional knockout of the mouse homolog of TFAP2C, Tcfap2c, in mouse mammary epithelium driven by MMTV-Cre promoted aberrant growth of the mammary tree leading to a reduction in the CD24(hi)/CD49f(mid) luminal cell population and concomitant gain of the CD24(mid)/CD49f(hi) basal cell population at maturity. Our results establish TFAP2C as a key transcriptional regulator for maintaining the luminal phenotype in human breast carcinoma. Furthermore, Tcfap2c influences development of the luminal cell type during mammary development. The data suggest that TFAP2C has an important role in regulated luminal-specific genes and may be a viable therapeutic target in breast cancer.

Transcriptional regulation of the GPX1 gene by TFAP2C and aberrant CpG methylation in human breast cancer.

The complexity of gene regulation has created obstacles to defining mechanisms that establish the patterns of gene expression characteristic of the different clinical phenotypes of breast cancer. TFAP2C is a transcription factor that has a critical role in the regulation of both estrogen receptor-alpha (ERα) and c-ErbB2/HER2 (Her2). Herein, we performed chromatin immunoprecipitation and direct sequencing (ChIP-seq) for TFAP2C in four breast cancer cell lines. Comparing the genomic binding sites for TFAP2C, we identified that glutathione peroxidase (GPX1) is regulated by TFAP2C through an AP-2 regulatory region in the promoter of the GPX1 gene. Knockdown of TFAP2C, but not the related factor TFAP2A, resulted in an abrogation of GPX1 expression. Selenium-dependent GPX activity correlated with endogenous GPX1 expression and overexpression of exogenous GPX1 induced GPX activity and significantly increased resistance to tert-butyl hydroperoxide. Methylation of the CpG island encompassing the AP-2 regulatory region was identified in cell lines where TFAP2C failed to bind the GPX1 promoter and GPX1 expression was unresponsive to TFAP2C. Furthermore, in cell lines where GPX1 promoter methylation was associated with gene silencing, treatment with 5'-aza-2-deoxycytidine (5'-aza-dC) (an inhibitor of DNA methylation) allowed TFAP2C to bind to the GPX1 promoter resulting in the activation of GPX1 RNA and protein expression. Methylation of the GPX1 promoter was identified in ∼20% of primary breast cancers and a highly significant correlation between the TFAP2C and GPX1 expression was confirmed when considering only those tumors with an unmethylated promoter, whereas the related factor, TFAP2A, failed to demonstrate a correlation. The results demonstrate that TFAP2C regulates the expression of GPX1, which influences the redox state and sensitivity to oxidative stress induced by peroxides. Given the established role of GPX1 in breast cancer, the results provide an important mechanism for TFAP2C to further influence oncogenesis and progression of breast carcinoma cells.

Validity and reproducibility of a web-based, self-administered food frequency questionnaire.

BACKGROUND/OBJECTIVES: To assess the validity and the reproducibility of a newly developed web-based, self-administered food frequency questionnaire (web-FFQ). SUBJECTS/METHODS: A total of 74 healthy subjects (34 men and 40 women) from the Québec City metropolitan area were asked to complete, in random order, the web-FFQ, a validated interviewer-administered FFQ (IA-FFQ) and a 3-day food record (3-day FR). RESULTS: Mean intakes of 17/22 nutrients assessed between the web-FFQ and the 3-day FR were not significantly different (differences <10%, P≥0.11). Sex and energy-adjusted de-attenuated Pearson correlation coefficients for each nutrient varied from 0.12-0.98 (mean R=0.55, 95% confidence interval 0.46; 0.63) between the web-FFQ and the 3-day FR. All correlations were significant (P≤0.01) and above 0.34 (mean R=0.59, 95% confidence interval 0.54; 0.65) between the web-FFQ and the IA-FFQ, except for sodium (R=0.17, P=0.14). Cross-classification analysis revealed that on average, 77% of subjects were classified in the same or adjacent quartile of nutrient intake between the web-FFQ and the 3-day FR. Correlation coefficients for reproducibility of the web-FFQ tested 4-6 weeks apart in the same individuals were all equal or above 0.48 (P≤0.0001; mean R=0.72, 95% confidence interval 0.68; 0.76). More than 90% of the subjects were classified in the same or adjacent quartile between the two administrations of the web-FFQ, while only 0.8% was misclassified. CONCLUSIONS: These data demonstrate that the newly developed web-based FFQ appears to have reasonable validity and good reproducibility for assessing nutrient intakes at the group and individual levels in a population of healthy adults.

Epidemiology of cutaneous melanoma in the French West Indies (Martinique).

The epidemiology of melanoma in populations of African-European descent has rarely been reported. The authors studied melanoma in the French West Indies (Martinique), where black Caribbeans and whites represented 96% and 4% of the population, respectively. Among the 85 cases of melanoma collected from 1976 to 1995, blacks represented 75% and whites, 25%. The average incidence rates were 1.48 and 0.9 per 100,000 per year in females and males, respectively. The sole of the foot represented 72% of the primary sites in blacks. Breslow's tumor thickness was > 1.5 mm in 68% of the cases. The 5-year survival was 44%.

Pituitary LH content and plasma LH levels following daily GnRH analogue treatment in male red-winged blackbirds (Agelaius phoeniceus).

1. During the 14-day treatment period, plasma LH levels following GnRH analogue (GnRH-A) injections (10.0 micrograms) were significantly reduced after the 6th and the 14th injection. 2. One day post-treatment, the LH pituitary content was significantly reduced in GnRH-A-treated redwings compared to saline-injected controls. 3. Pituitary LH content was significantly higher in GnRH-A treated birds compared to control birds 14 and 28 days post-treatment and plasma LH levels were similar in both groups. 4. Hypersecretion of LH following GnRH-A injections appears to reduce pituitary LH content, acting as a stimulus for its synthesis. 5. These results suggest a higher LH synthesis and storage in the pituitary gland of the GnRH-A-treated birds compared to the control birds during the post-treatment period.

Comparative trial of administration of half (0.05 mg) and quarter (0.025 mg) dose of intradermal Pasteur BCG on 291 infants from birth to 1 year in French Guyana.

The study concerns 291 newborns and infants aged 0 to 1 year placed randomly in two groups which respectively received 0.025 and 0.05 mg Pasteur BCG by intradermal injection, between 1 December 1988 and 28 February 1989. This random test aimed to determine if the administration of one quarter dose (0.025 mg) of intradermal BCG conferred immunity comparable to that of one half (0.05 mg) while diminishing the risk of complications, in particular suppurative adenopathy, in infants of ages 0-1 year. Statistical analysis of the results showed that the 0.025 mg dose of intradermal BCG entails an immunoresponse as satisfactory as that entailed by the 0.05 mg dose, while the rate of suppurative adenitis is significantly higher in the group that received the 0.05 mg dose. It is therefore well justified to recommend a dose of 0.025 mg of intradermal Pasteur BCG for infants aged 1 year and less.

Plasma LH and androgen levels in the red-winged blackbird (Agelaius phoeniceus) treated with a potent GnRH analogue.

1. Low doses of GnRH-A (0.01-0.10-1.0 micrograms) given during the annual testes growth period did not clearly affect plasma LH and androgen levels 10 min following the injection. 2. The first injection of high doses of GnRH-A (2.0-10.0-20.0 micrograms) markedly increased plasma LH and androgen levels measured 10 min following the injection. The increase in plasma LH level was dose-dependent and the maximal LH level was obtained with 10.0 micrograms of GnRH-A. 3. Impairment of the LH response to GnRH-A was assessed by comparing the first and the fourteenth injection of high doses of GnRH-A. Evidences of pituitary gland desensitization are reported since plasma LH levels were reduced following the fourteenth injection in all groups. 4. Plasma androgen levels following high doses of GnRH-A were not clearly affected in red-winged blackbirds.

Choice behaviour of red-winged blackbirds (Agelaius phoeniceus ) searching for food: The role of certain variables in stay and shift strategies.

This experiment examined the extent to which the food searching strategies of Red-winged Blackbirds are influenced by the age of the birds and by information about the food supply gained from a previously visited location. Birds entered a maze and were given a choice between the three parallel, foraging locations. After making its choice, each bird was either allowed to consume all of the food present at the site (depletion condition) or only some of it (non-depletion condition). All birds were tested under both conditions. After its first choice, each bird was subsequently re-tested to determine if it returned to the previously visited site or whether it chose an alternate site. Subjects were more likely to choose an alternate location after experiencing the depletion condition. Under the non-depletion condition, adult birds showed a strong predisposition to return to the initially chosen sites while immature birds only returned to those sites randomly. The results were related to the current theory of staying/shifting dichotomy.

Proxy case mix measures for nursing homes.

Nursing home case mix measures are needed for the same purposes that spurred the intensive development of case mix measures for hospitals: management and planning decisions, organizational performance research, and reimbursement policy analysis. This paper develops and validates a pair of complementary measures that are simple to compute, are easy to interpret, and use generally available data. They are not, however, definitive. A secondary purpose of this paper is thus to galvanize the development of data bases that will give rise to superior case mix measures for nursing homes.

Health services administrator role delineation methodology: an institutional long-term care example.

Health services administrators (HSA) are the cynosure of much current research because of their pivotal positions vis-a-vis quality of care and cost-effective policies. Role delineation methods used to date are too simple and/or too subjective to reflect the actual complexities of these roles. Dimensional analysis, as used to delineate complex organizational processes, more succinctly and accurately reflects these complexities and is more objective. The inherent weakness of dimensional analysis in devising the initial list of tasks can be counteracted by the use of facet analysis. A set of LTC administrator tasks from a national study is dimensionally analyzed to produce a role delineation and the subroles are validated through criterion analyses and amplified through reference to the literature. A similar strategy could usefully and readily be applied to extant data sets for other HSAs.

Physician receptivity to nurse practitioners: a study of the correlates of the delegation of clinical responsibility.

A survey to measure physician receptivity to nurse practitioners was conducted in North Carolina in 1973. All North Carolina physicians were asked to rate a list of 35 clinical tasks of varying levels of difficulty and responsibility according to their willingness to delegate these tasks to nurse practitioners. Using eight items from this list that were good discriminants of physician attitudes towards delegating responsibility, task delegation scores were correlated with physician characteristics and their responses to questions about recruitment, training, reimbursement, and willingness to hire nurse practitioners. Thirty-four per cent of the respondents would hire a nurse practitioner, whereas 52% approved of the concept but would not hire one. Physicians who had previously worked with a nurse practitioner were more willing to hire one and had a higher task delegation score. Sixty-eight per cent of respondents would share their load with nurse practitioners in their offices, while 6% would have them work in satellite clinics away from the physicians' offices. Most physicians wanted their own nurse trained as a nurse practitioner in a program that combined a didactic course at a medical center with on-the-job training. The authors conclude that there is a potential demand for nurse practitioners in North Carolina and that the training program must prepare the nurse practitioners for the tasks physicians are willing to delegate to them.