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Background The association between and vitamin D levels and fractures is uncertain. Objective To test the hypothesis that serum 25-hydroxyVitamin D (25(OH) vitamin D) levels are associated with the risk of hip fracture in community dwelling women. Design Nested case-control study. Setting 40 US clinical centers. Participants We studied 400 cases of incident hip fractures and 400 controls matched on age, race/ethnicity and date of blood draw (average follow-up time, 7.1 years). Subjects were selected from 39,795 postmenopausal women without previous hip fractures, not using estrogens or other bone-active therapies. Measurements Serum 25(OH) vitamin D was measured on baseline serum using radioimmunoassay with DiaSorin reagents and divided into quartiles. Conditional logistic regression was used to estimate the odds ratio with 95% confidence intervals (CI). Multivariable models included age, body mass index, parental and personal history of fractures, smoking, alcohol and calcium intake, geographic location and corticosteroid use. Results The mean (standard deviation, SD) 25(OH) vitamin D (nM) was lower in cases, 56.2(20.3) compared to controls, 59.7(18), p=0.007. A 25 nM (10ng/ml) decrease in 25(OH) vitamin D was associated with a 33% increased risk of hip fracture (odds ratio=1.33; 95%CI,1.06, 1.68) in multivariable models. Compared to women with 25(OH) vitamin D ≥70.7 nM (Quartile 4), the odds ratio of hip fracture was 1.71 (1.05, 2.79), 1.09 (0.70, 1.71) and 0.82 (0.51, 1.31) in women with 25(OH) vitamin D <47.5 nM, 47.5 to 60 nM, 60 to <70 nM, respectively, p trend =0.015. This association was in part mediated by a marker of bone resorption but remained statistically significant. Adjustment for falls, physical function, frailty, renal function, or sex steroid hormones had no effect on this association. Limitations No measure of bone density. Conclusion Low serum 25(OH) vitamin D concentrations are associated with a higher risk of hip fracture. Measurement of 25(OH) vitamin D may be useful in identifying women at high risk of hip fracture.

Relation of BMI and physical activity to sex hormones in postmenopausal women. Obesity. 2006; 14:1662-1677. Objective: Levels of estrogen, androgen, and prolactin have been related to risk of postmenopausal breast cancer. However, the determinants of these hormone concentrations are not established. The purpose of this study was to examine correlates of endogenous sex hormones. Research Methods and Procedures: Associations among adiposity, physical activity, and diet and concentrations of estradiol, free estradiol, estrone, testosterone, free testosterone, sex hormone-binding globulin (SHBG), androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and prolactin were evaluated in 267 postmenopausal women randomly selected from the Women's Health Initiative Dietary Modification Trial. Results:In multiple regression analyses on log-transformed hormones, BMI was positively associated with estrone (␤ ϭ 0.031, p Ͻ 0.001), estradiol (␤ ϭ 0.048, p Ͻ 0.001), free estradiol (␤ ϭ 0.062, p Ͻ 0.001), free testosterone (␤ ϭ 0.017, p ϭ 0.02), and prolactin (␤ ϭ 0.012, p ϭ 0.02) and negatively associated with SHBG (␤ ϭ Ϫ0.02, p ϭ 0.001). Total physical activity (metabolic equivalent tasks per week) was negatively associated with concentrations of estrone, estradiol, and androstenedione (␤ ϭ Ϫ0.006, Ϫ0.007, and Ϫ0.005, respectively, all p Յ 0.05). Using a composite variable of BMI and physical activity dichotomized by median values, women with high BMI/low physical activity had a mean estrone concentration of 28.8 pg/ mL, compared with 24.1, 19.9, and 18.4 pg/mL for women with high BMI/high physical activity, low BMI/low physical activity, and low BMI/high physical activity, respectively (p trend Ͻ 0.001). Similar trends were observed for estradiol and free estradiol and, in inverse, for SHBG. Discussion: These associations may, in part, explain the positive associations between overweight/obesity and a sedentary lifestyle on breast cancer risk.

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Background-Prehypertension is common and is associated with increased vascular mortality. The extent to which it increases risk of nonfatal myocardial infarction, stroke, and congestive heart failure is less clear.

BackgroundCA125, human epididymis protein 4 (HE4), mesothelin, B7-H4, decoy receptor 3 (DcR3), and spondin-2 have been identified as potential ovarian cancer biomarkers. Except for CA125, their behavior in the prediagnostic period has not been evaluated.MethodsImmunoassays were used to determine concentrations of CA125, HE4, mesothelin, B7-H4, DcR3, and spondin-2 proteins in prediagnostic serum specimens (1–11 samples per participant) that were contributed 0–18 years before ovarian cancer diagnosis from 34 patients with ovarian cancer (15 with advanced-stage serous carcinoma) and during a comparable time interval before the reference date from 70 matched control subjects who were participating in the Carotene and Retinol Efficacy Trial. Lowess curves were fit to biomarker levels in cancer patients and control subjects separately to summarize mean levels over time. Receiver operating characteristic curves were plotted, and area-under-the curve (AUC) statistics were computed to summarize the discrimination ability of these biomarkers by time before diagnosis.ResultsSmoothed mean concentrations of CA125, HE4, and mesothelin (but not of B7-H4, DcR3, and spondin-2) began to increase (visually) in cancer patients relative to control subjects approximately 3 years before diagnosis but reached detectable elevations only within the final year before diagnosis. In descriptive receiver operating characteristic analyses, the discriminatory power of these biomarkers was limited (AUC statistics range = 0.56–0.75) but showed increasing accuracy with time approaching diagnosis (eg, AUC statistics for CA125 were 0.57, 0.68, and 0.74 for ≥4, 2–4, and <2 years before diagnosis, respectively).ConclusionSerum concentrations of CA125, HE4, and mesothelin may provide evidence of ovarian cancer 3 years before clinical diagnosis, but the likely lead time associated with these markers appears to be less than 1 year.

Infection of porcine alveolar macrophages by the porcine reproductive and respiratory syndrome virus (PRRSV) was significantly enhanced in vitro by antibody raised against the PRRSV isolate ISU-P (p < 0.01). Increased yields and infection rates were highly correlated (r = 0.95) and the ratio of yield to infection rate was greater than 1.4, suggesting that more than one mechanism was responsible for enhanced infection. Antibody-dependent enhancement (ADE) of infection was also demonstrated in vivo using a completely randomized block design (n = 16). The mean level and duration of viremia were greater (p < 0.05) in pigs injected with subneutralizing amounts of PRRSV-specific IgG prior to virus challenge than in control pigs injected with normal IgG. In contrast, virus replication was significantly (p < 0.01) inhibited in pigs with neutralizing antibody titers of 4 log2. The period of time that subneutralizing levels of antibody can persist and contribute to ADE of PRRSV infection was estimated in 4 pigs injected with PRRSV-specific IgG to yield an initial neutralizing antibody titer of 3.8 log2. Neutralizing activity declined to undetectable levels by day 37 postinjection (PI). ADE activity was first detected in undiluted sera on day 20 PI and persisted through day 62 PI. Western immunoblot analysis of sera collected between days 37 and 62 PI detected antibodies specific for the 15-kDa nucleocapsid and 26-kDa glycosylated envelope proteins. These results strongly suggest that ADE has the potential to contribute to the pathogenesis of PRRSV infection and is mediated by antibody specific for the 26-kDa envelope protein.

To identify risk factors for fractures in multi-ethnic women, we studied 159,579 women enrolled in the Women's Health Initiative. In general, risk factors for fractures were similar across ethnic groups. However, irrespective of their ethnicity, women with multiple risk factors have a high risk of fracture. Targeting these high-risk women for screening and intervention could reduce fractures. Introduction:Fracture rates tend to be lower in minority women, but consequences may be greater. In addition, the number of fractures is expected to increase in minority women because of current demographic trends. There are limited prospective data on risk factors for fractures in minority women. Materials and Methods:We studied 159,579 women 50-79 yr of age enrolled in the Women's Health Initiative. Information on risk factors was obtained by questionnaire or examination. Nonspine fractures that occurred after study entry were identified over an average follow-up of 8 ± 2.6 (SD) yr. Results: Annualized rates (%) of fracture in whites, blacks, Hispanics, Asians, and American Indians were 2.0, 0.9, 1.3, 1.2, and 2.0, respectively. Significant predictors [HR (95% CI)] of fractures by ethnic group were as follows: blacks: at least a high school education, 1.22 (1.0, 1.5); (+) fracture history, 1.7 (1.4, 2.2); and more than two falls, 1.7 (1.9, 2.0); Hispanics: height (>162 cm), 1.6 (1.1, 2.2); (+) fracture history, 1.9 (1.4, 2.5); more than two falls, 1.8 (1.4, 2.3); arthritis, 1.3 (1.1, 1.6); corticosteroid use, 3.9 (1.9, 8.0); and parental history of fracture, 1.3 (1.0, 1.6); Asians: age (per 5 yr), 1.2 (1.0, 1.3); (+) fracture history, 1.5 (1.1, 2.0); current hormone therapy (HT), 0.7 (0.5, 0.8); parity (at least five), 1.8 (1.1, 3.0); more than two falls, 1.4 (1.1, 1.9); American Indian: (+) fracture history, 2. 9 (1.5, 5.7); current HT, 0.5 (0.3, 0.9). Women with eight or more risk factors had more than a 2-fold higher rate of fracture compared with women with four or fewer risk factors. Two ethnicity × risk factor interactions were identified: age and fall history. Conclusions: Irrespective of their ethnicity, women with multiple risk factors have a high risk of fracture. Targeting these high-risk women for screening and intervention could reduce fractures.