Pregnancy Inhibits Mammary Carcinogenesis by Persistently Altering the Hypothalamic-Pituitary Axis.

Early full-term pregnancy is known to reduce the lifetime risk of breast cancer. Although the phenomenon of parity-induced protection is well-established, the physiological mechanisms involved in this protection are not clear. Earlier reports have shown that pregnancy results in alterations of hormone levels. How pregnancy affects hypothalamic hormones and how the change, if any, influences breast cancer is not well understood. Seven-week-old female Lewis rats were given N-methyl-N-nitrosourea. Two weeks post carcinogen exposure, a set of females were housed with males to generate the parous rats and another set of rats served as the nulliparous controls. Mammary tumorigenesis was assessed for 9 months. Hypothalamic and pituitary levels of hormones were measured at various timepoints. Further, animals were also challenged with growth hormone and prolactin secretagogues to test the effect of pregnancy on the hypothalamic-pituitary hormonal axis. Persistent alterations in the level of growth hormone-releasing hormone, thyrotropin releasing hormone, dopamine, and somatostatin in the hypothalamus of parous animals was observed. Further, we also observed that pregnancy had a significant effect on the pituitary gland and its response to growth hormone and prolactin secretagogues. Our studies using the rodent model system demonstrate that pregnancy could be reducing the risk of breast cancer by persistently altering the hypothalamic-pituitary axis, which could have implications for breast cancers in humans as well.

Growth dynamics of juvenile loggerhead sea turtles undergoing an ontogenetic habitat shift.

Ontogenetic niche theory predicts that individuals may undergo one or more changes in habitat or diet throughout their lifetime to maintain optimal growth rates, or to optimize trade-offs between mortality risk and growth. We combine skeletochronological and stable nitrogen isotope (δ15N) analyses of sea turtle humeri (n = 61) to characterize the growth dynamics of juvenile loggerhead sea turtles (Caretta caretta) during an oceanic-to-neritic ontogenetic shift. The primary objective of this study was to determine how ontogenetic niche theory extends to sea turtles, and to individuals with different patterns of resource use (discrete shifters, n = 23; facultative shifters n = 14; non-shifters, n = 24). Mean growth rates peaked at the start of the ontogenetic shift (based on change in δ15N values), but returned to pre-shift levels within 2 years. Turtles generally only experienced 1 year of relatively high growth, but the timing of peak growth relative to the start of an ontogenetic shift varied among individuals (before, n = 14; during, n = 12; after, n = 8). Furthermore, no reduction in growth preceded the transition, as is predicted by ontogenetic niche theory. Annual growth rates were similar between non-transitioning turtles resident in oceanic and neritic habitats and turtles displaying alternative patterns of resource use. These results suggest that factors other than maximization of size-specific growth may more strongly influence the timing of ontogenetic shifts in loggerhead sea turtles, and that alternative patterns of resource use may have limited influence on somatic growth and age at maturation in this species.

Yield of Urinalysis Screening in Pediatric Cancer Survivors.

BACKGROUND: The Children's Oncology Group (COG) publishes consensus guidelines with screening recommendations for early identification of treatment-related morbidities among childhood cancer survivors. We sought to estimate the yield of recommended yearly urinalysis screening for genitourinary complications as per Version 3.0 of the COG Long-Term Follow-Up Guidelines and identify possible risk factors for abnormal screening in a survivor population. PROCEDURE: A database of pediatric cancer survivors evaluated between January 2008 and March 2012 at Children's Healthcare of Atlanta was queried for survivors at risk for genitourinary late effects. The frequency of abnormal urinalyses (protein ≥1+ and/or presence of glucose and/or ≥5 red blood cells per high power field) was estimated. Risk factors associated with abnormal screening were identified. RESULTS: Chart review identified 773 survivors (57% male; 67% Caucasian; 60% leukemia/lymphoma survivors; mean age at diagnosis, 5.7 years [range: birth to 17.7 years]; time from diagnosis to initial screening, 7.6 years [range: 2.3 to 21.5 years]) who underwent urinalysis. Abnormal results were found in 78 (5.3%) of 1,484 total urinalyses. Multivariable analysis revealed higher dose ifosfamide (odds ratio [OR] = 6.8, 95% confidence interval [CI] 2.9-16.0) and total body irradiation (TBI, OR = 3.0, 95% CI 1.0-8.4) as significant risk factors for abnormal initial urinalysis screening. CONCLUSIONS: Pediatric cancer survivors exposed to higher dose ifosfamide or TBI may be at higher risk of abnormal findings on urinalysis screening. Targeted screening of these higher risk patients should be considered.

Effects of demineralization on the stable isotope analysis of bone samples.

RATIONALE: The sampling of sequential, annually formed bone growth layers for stable carbon (δ(13)C values) and nitrogen (δ(15)N values) isotope analysis (SIA) can provide a time series of foraging ecology data. To date, no standard protocol exists for the pre-SIA treatment of cortical samples taken from fresh, modern, bones. METHODS: Based on the SIA of historical bone, it is assumed that fresh bone samples must be pre-treated with acid prior to SIA. Using an elemental analyzer coupled to an isotope ratio mass spectrometer to measure stable carbon and nitrogen ratios, we tested the need to acidify cortical bone powder with 0.25 M HCl prior to SIA to isolate bone collagen for the determination of δ(13)C and δ(15)N values. We also examined the need for lipid extraction to remove potential biases related to δ(13)C analysis, based on a C:N ratio threshold of 3.5. RESULTS: It was found that acidification of micromilled cortical bone samples from marine turtles does not affect their δ(15)N values, and the small effect acidification has on δ(13)C values can be mathematically corrected for, thus eliminating the need for pre-SIA acidification of cortical bone. The lipid content of the cortical bone samples was low, as measured by their C:N ratios, indicating that lipid extracting cortical bone samples from modern marine turtles is unnecessary. CONCLUSIONS: We present a standard protocol for testing fresh, modern cortical bone samples prior to SIA, facilitating direct comparison of future studies. Based on the results obtained from marine turtle bones, pre-acidification and lipid removal of cortical bone are not recommended. This is especially useful as there is frequently not enough bone material removed via micromilling of sequential growth layers to accommodate both acid treatment and SIA.