Throughout evolution, exposure to sunlight and the photosynthesis of vitamin D 3 in the skin has been critically important for the evolution of land vertebrates. During exposure to sunlight, the solar UVB photons with energies 290-315 nm are absorbed by 7-dehydrocholesterol in the skin and converted to previtamin D 3 . Previtamin D 3 undergoes a rapid transformation within the plasma membrane to vitamin D 3 . Excessive exposure to sunlight will not result in vitamin D intoxication because both previtamin D 3 and vitamin D 3 are photolyzed to several noncalcemic photoproducts. During the winter at latitudes above ∼35°, there is minimal, if any, previtamin D 3 production in the skin. Altitude also has a significant effect on vitamin D 3 production. At 27°N in November, very little (∼0.5%) previtamin D 3 synthesis was detected in Agra (169 m) and Katmandu (1400 m). There was an ∼2-and 4-fold increase in previtamin D 3 production at ∼3400 m and at Everest base camp (5300 m), respectively. Increased skin pigmentation, application of a sunscreen, aging, and clothing have a dramatic effect on previtamin D 3 production in the skin. It is estimated that exposure in a bathing suit to 1 minimal erythemal dose (MED) is equivalent to ingesting between 10,000 and 25,000 IU of vitamin D 2 . The importance of sunlight for providing most humans with their vitamin D requirement is well documented by the seasonal variation in circulating levels of 25-hydroxyvitamin D [25(OH)D]. Vitamin D deficiency [i.e., 25(OH)D < 20 ng/ml] is common in both children and adults worldwide. Exposure to lamps that produce UVB radiation is an excellent source for producing vitamin D 3 in the skin and is especially efficacious in patients with fat malabsorption syndromes. The major cause of vitamin D deficiency globally is an underappreciation of sunlight's role in providing humans with their vitamin D 3 requirement. Very few foods naturally contain vitamin D, and those that do have a very variable vitamin D content. Recently it was observed that wild caught salmon had between 75% and 90% more vitamin D 3 compared with farmed salmon. The associations regarding increased risk of common deadly cancers, autoimmune diseases, infectious diseases, and cardiovascular disease with living at higher latitudes and being prone to vitamin D deficiency should alert all health care professionals about the importance of vitamin D for overall health and well being.

The purpose of this work was to determine the effects of varying levels of dietary protein on body composition and muscle protein synthesis during energy deficit (ED). A randomized controlled trial of 39 adults assigned the subjects diets providing protein at 0.8 (recommended dietary allowance; RDA), 1.6 (2×-RDA), and 2.4 (3×-RDA) g kg(-1) d(-1) for 31 d. A 10-d weight-maintenance (WM) period was followed by a 21 d, 40% ED. Body composition and postabsorptive and postprandial muscle protein synthesis were assessed during WM (d 9-10) and ED (d 30-31). Volunteers lost (P<0.05) 3.2 ± 0.2 kg body weight during ED regardless of dietary protein. The proportion of weight loss due to reductions in fat-free mass was lower (P<0.05) and the loss of fat mass was higher (P<0.05) in those receiving 2×-RDA and 3×-RDA compared to RDA. The anabolic muscle response to a protein-rich meal during ED was not different (P>0.05) from WM for 2×-RDA and 3×-RDA, but was lower during ED than WM for those consuming RDA levels of protein (energy × protein interaction, P<0.05). To assess muscle protein metabolic responses to varied protein intakes during ED, RDA served as the study control. In summary, we determined that consuming dietary protein at levels exceeding the RDA may protect fat-free mass during short-term weight loss.

Background: It has been demonstrated that extracellular mRNA can be detected in the circulation. Our hypothesis was that circulating miRNAs are also present and differentially expressed in the serum of breast cancer patients compared to controls.

Summary To evaluate the feasibility of nipple aspiration and to identify intermediate markers of breast cancer risk, nipple aspirate fluid (NAF) was collected from 177 subjects using a modified breast pump. The first 33 subjects demonstrated that we could obtain NAF quickly, reliably and repeatedly. Specimens from the remaining 144 (Giuliano, 1994). Additional screening tools to identify precancer and early breast cancer are urgently needed.Although the early detection of breast cancer will lead to a higher cure rate, the ideal form of treatment is prevention. The prevention of breast cancer is hindered by the difficulty in identifying an effective agent. Effective agents are difficult to identify in part because of the long period required for breast cancer to develop and, consequently, the requirement for lengthy clinical trials to test the efficacy of the agent, if the end point is the prevention of cancer. One way to shorten the time to finding of an effective agent is the identification of intermediate biomarkers, which are biological alterations in cells or tissue that occur between the time of initiation and tumour invasion. The theory is that an agent that partially or completely reverses the intermediate biomarker back to a normal phenotype may be interrupting carcinogenesis. Validation of the biomarker would require that the agent also decrease the incidence of cancer. Evaluating the effect of the agent requires the analysis of tissue, cells or non-cellular fluid. Nipple

Trans-resveratrol, present in high concentration in the skin of red grapes and red wine, has a dose-dependent antiproliferative effect in vitro, prevents the formation of mammary tumors, and has been touted as a chemopreventive agent. Based upon in vitro studies demonstrating that trans-resveratrol downregulates the expression of 1) DNA methyltransferases and 2) the cancer promoting prostaglandin (PG)E2, we determined if trans-resveratrol had a dose-related effect on DNA methylation and prostaglandin expression in humans. Thirty-nine adult women at increased breast cancer risk were randomized in double-blind fashion to placebo, 5 or 50 mg trans-resveratrol twice daily for 12 wk. Methylation assessment of 4 cancer-related genes (p16, RASSF-1α, APC, CCND2) was performed on mammary ductoscopy specimens. The predominant resveratrol species in serum was the glucuronide metabolite. Total trans-resveratrol and glucuronide metabolite serum levels increased after consuming both trans-resveratrol doses (P < .001 for both). RASSF-1α methylation decreased with increasing levels of serum trans-resveratrol (P = .047). The change in RASSF-1α methylation was directly related to the change in PGE2 (P = .045). This work provides novel insights into the effects of trans-resveratrol on the breast of women at increased breast cancer risk, including a decrease in methylation of the tumor suppressor gene RASSF-1α. Because of the limited sample size, our findings should be validated in a larger study.