The redox potential and the natural antibody (NAb) levels are parameters commonly tested to verify the physiological response to stressful situations determined by farming conditions or research ...needs. In this paper, the redox potential, assessed by different spectrophotometric methods, was related to NAb levels together with total immunoglobulin (tot-Ig) levels in goat kid serum. Reactive oxygen metabolites (ROMs) and ceruloplasmin (CP) oxidase activity were significantly associated with NAb-IgG and NAb-IgM. Nitric oxide metabolites (NOx) and total thiol levels (TTLs) were significantly related to NAb-IgM and tot-IgM, and with NAb-IgG, respectively. A tendency was shown between ROMs and tot-IgM, and between CP and tot-IgM, where, however, the significance levels were above the cut-off values. Total oxidant status (TOS), total antioxidant activity (TAA), determined by the ABTS-based method, the ferric reducing ability of plasma (FRAP), and free radical scavenging activity (FRSA) were associated with neither NAb nor tot-Ig. The obtained results are discussed in light of the possible linkage between the (anti)oxidant status and the innate immune system in goats.
•Relationship between natural antibodies (NAbs) and (anti)oxidant parameters in kid serum was studied.•ROMs and CP oxidase activity were significantly associated with both NAb-IgG and NAb-IgM.•NOx and TTLs were significantly associated with NAb-IgM, and with NAb-IgG, respectively.•A linkage between the redox potential and NAb levels in goat kid was demonstrated.
Background: Initial findings from the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial (P-1) demonstrated that tamoxifen reduced the risk of estrogen ...receptor–positive tumors and osteoporotic fractures in women at increased risk for breast cancer. Side effects of varying clinical significance were observed. The trial was unblinded because of the positive results, and follow-up continued. This report updates our initial findings. Methods: Women (n = 13 388) were randomly assigned to receive placebo or tamoxifen for 5 years. Rates of breast cancer and other events were compared by the use of risk ratios (RRs) and 95% confidence intervals (CIs). Estimates of the net benefit from 5 years of tamoxifen therapy were compared by age, race, and categories of predicted breast cancer risk. Statistical tests were two-sided. Results: After 7 years of follow-up, the cumulative rate of invasive breast cancer was reduced from 42.5 per 1000 women in the placebo group to 24.8 per 1000 women in the tamoxifen group (RR = 0.57, 95% CI = 0.46 to 0.70) and the cumulative rate of noninvasive breast cancer was reduced from 15.8 per 1000 women in the placebo group to 10.2 per 1000 women in the tamoxifen group (RR = 0.63, 95% CI = 0.45 to 0.89). These reductions were similar to those seen in the initial report. Tamoxifen led to a 32% reduction in osteoporotic fractures (RR = 0.68, 95% CI = 0.51 to 0.92). Relative risks of stroke, deep-vein thrombosis, and cataracts (which increased with tamoxifen) and of ischemic heart disease and death (which were not changed with tamoxifen) were also similar to those initially reported. Risks of pulmonary embolism were approximately 11% lower than in the original report, and risks of endometrial cancer were about 29% higher, but these differences were not statistically significant. The net benefit achieved with tamoxifen varied according to age, race, and level of breast cancer risk. Conclusions: Despite the potential bias caused by the unblinding of the P-1 trial, the magnitudes of all beneficial and undesirable treatment effects of tamoxifen were similar to those initially reported, with notable reductions in breast cancer and increased risks of thromboembolic events and endometrial cancer. Readily identifiable subsets of individuals comprising 2.5 million women could derive a net benefit from the drug.
Twelve milking Girgentana goats were allocated into 3 groups and fed 3 diets ad libitum in a 3×3 Latin square design with 3 periods. The diets were Sulla fresh forage ad libitum (SUL), Sulla fresh ...forage ad libitum and 800g/d of barley meal (SULB), and mixed hay ad libitum and 800g/d of barley meal (HB). Changes were observed in total polyphenol intake, plasma oxidative status, plasma polyphenol content, metabolic status, milk polyphenol content, and total antioxidant capacity. The fresh forage diets (SUL and SULB) increased dry matter, total polyphenol, nontannic polyphenol and tannin intakes, and the milk total protein, casein, milk total polyphenols, and milk free polyphenols compared with the HB diet. The intake of condensed tannins was higher in the SUL than in the HB group, and an intermediate value was recorded for the SULB group. Plasma from the SUL- and SULB-fed goats exhibited greater total antioxidant capacity and greater total polyphenol and free polyphenol levels compared with the plasma from the HB group. Positive correlations between plasma total antioxidant capacity and condensed tannins intake (r=0.43), plasma total polyphenol and total polyphenol intake (r=0.61), and plasma free polyphenol and milk total polyphenols (r=0.38) were observed. The correlation between milk free polyphenols and whey total antioxidant capacity (r=0.42) highlights the role of free polyphenols in the determination of the antioxidant activity of milk. These results indicate that Sulla fresh forage exerts an antioxidant activity due to its secondary compounds that provide additional antioxidant value and that Sulla forage appears to be a promising strategy for improving product quality.
Summary Background Ductal carcinoma in situ is currently managed with excision, radiotherapy, and adjuvant hormone therapy, usually tamoxifen. We postulated that an aromatase inhibitor would be safer ...and more effective. We therefore undertook this trial to compare anastrozole versus tamoxifen in postmenopausal women with ductal carcinoma in situ undergoing lumpectomy plus radiotherapy. Methods The double-blind, randomised, phase 3 National Surgical Adjuvant Breast and Bowel Project (NSABP) B-35 trial was done in 333 participating NSABP centres in the USA and Canada. Postmenopausal women with hormone-positive ductal carcinoma in situ treated by lumpectomy with clear resection margins and whole-breast irradiation were enrolled and randomly assigned (1:1) to receive either oral tamoxifen 20 mg per day (with matching placebo in place of anastrozole) or oral anastrozole 1 mg per day (with matching placebo in place of tamoxifen) for 5 years. Randomisation was stratified by age (<60 vs ≥60 years) and patients and investigators were masked to treatment allocation. The primary outcome was breast cancer-free interval, defined as time from randomisation to any breast cancer event (local, regional, or distant recurrence, or contralateral breast cancer, invasive disease, or ductal carcinoma in situ), analysed by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00053898 , and is complete. Findings Between Jan 1, 2003, and June 15, 2006, 3104 eligible patients were enrolled and randomly assigned to the two treatment groups (1552 to tamoxifen and 1552 to anastrozole). As of Feb 28, 2015, follow-up information was available for 3083 patients for overall survival and 3077 for all other disease-free endpoints, with median follow-up of 9·0 years (IQR 8·2–10·0). In total, 212 breast cancer-free interval events occurred: 122 in the tamoxifen group and 90 in the anastrozole group (HR 0·73 95% CI 0·56–0·96, p=0·0234). A significant time-by-treatment interaction (p=0·0410) became evident later in the study. There was also a significant interaction between treatment and age group (p=0·0379), showing that anastrozole is superior only in women younger than 60 years of age. Adverse events did not differ between the groups, except for thrombosis or embolism—a known side-effect of tamoxifen—for which there were 17 grade 4 or worse events in the tamoxifen group versus four in the anastrozole group. Interpretation Compared with tamoxifen, anastrozole treatment provided a significant improvement in breast cancer-free interval, mainly in women younger than 60 years of age. This finding means that women will benefit from having a choice of effective agents for ductal carcinoma in situ. Funding US National Cancer Institute and AstraZeneca Pharmaceuticals LP.
MoEDAL is designed to identify new physics in the form of stable or pseudostable highly ionizing particles produced in high-energy Large Hadron Collider (LHC) collisions. Here we update our previous ...search for magnetic monopoles in Run 2 using the full trapping detector with almost four times more material and almost twice more integrated luminosity. For the first time at the LHC, the data were interpreted in terms of photon-fusion monopole direct production in addition to the Drell-Yan-like mechanism. The MoEDAL trapping detector, consisting of 794 kg of aluminum samples installed in the forward and lateral regions, was exposed to 4.0 fb^{-1} of 13 TeV proton-proton collisions at the LHCb interaction point and analyzed by searching for induced persistent currents after passage through a superconducting magnetometer. Magnetic charges equal to or above the Dirac charge are excluded in all samples. Monopole spins 0, ½, and 1 are considered and both velocity-independent and-dependent couplings are assumed. This search provides the best current laboratory constraints for monopoles with magnetic charges ranging from two to five times the Dirac charge.
The selective estrogen-receptor modulator (SERM) tamoxifen became the first U.S. Food and Drug Administration (FDA)-approved agent for reducing breast cancer risk but did not gain wide acceptance for ...prevention, largely because it increased endometrial cancer and thromboembolic events. The FDA approved the SERM raloxifene for breast cancer risk reduction following its demonstrated effectiveness in preventing invasive breast cancer in the Study of Tamoxifen and Raloxifene (STAR). Raloxifene caused less toxicity (versus tamoxifen), including reduced thromboembolic events and endometrial cancer. In this report, we present an updated analysis with an 81-month median follow-up. STAR women were randomly assigned to receive either tamoxifen (20 mg/d) or raloxifene (60 mg/d) for 5 years. The risk ratio (RR; raloxifene:tamoxifen) for invasive breast cancer was 1.24 (95% confidence interval CI, 1.05-1.47) and for noninvasive disease, 1.22 (95% CI, 0.95-1.59). Compared with initial results, the RRs widened for invasive and narrowed for noninvasive breast cancer. Toxicity RRs (raloxifene:tamoxifen) were 0.55 (95% CI, 0.36-0.83; P = 0.003) for endometrial cancer (this difference was not significant in the initial results), 0.19 (95% CI, 0.12-0.29) for uterine hyperplasia, and 0.75 (95% CI, 0.60-0.93) for thromboembolic events. There were no significant mortality differences. Long-term raloxifene retained 76% of the effectiveness of tamoxifen in preventing invasive disease and grew closer over time to tamoxifen in preventing noninvasive disease, with far less toxicity (e.g., highly significantly less endometrial cancer). These results have important public health implications and clarify that both raloxifene and tamoxifen are good preventive choices for postmenopausal women with elevated risk for breast cancer.
This study proposed the General Health Index of Cheese (GHIC) as an indicator for the presence of health-promoting compounds in cheese and compared the antioxidant capacity and phenolic and fatty ...acid contents of cheeses from goats consuming 7 forage species. Ninety-one homogeneous Red Syrian goats were randomly assigned to 1 of 7 feeding treatments (Festuca arundinacea, Hordeum vulgare, Triticosecale, Pisum sativum, Trifolium alexandrinum, Vicia sativa, and Vicia faba minor). The housed goat groups received the scheduled forage ad libitum. Forage species affected the antioxidant capacity, the phenolic and fatty acid contents, the Health Promoting Index, and the GHIC. Trifolium alexandrinum, Triticosecale, and Hordeum vulgare showed a clear advantage in terms of beneficial fatty acids content in goat cheese. Cheese from the Triticosecale group also showed a high antioxidant capacity value even if its polyphenol content was intermediate compared with others. Trifolium alexandrinum and Triticosecale had the highest value of the new index GHIC. This comparison suggests that there are important differences in fatty acid profile and polyphenol content among cheeses from goats fed grasses and legumes commonly used in the Mediterranean area. In this first approach, GHIC index, which combines the positive components found in cheese, seems to be a useful tool to provide an indication concerning the general health value of the product.
The annual timing of temperate forest leaf colouring is affected by climate change; to date, its modelling remains a challenge. We take advantage of a
ca. 400 leaf colouring observations database ...acquired in France during the period of 1997–2006 in order to develop a new modelling framework aimed at predicting the spatial and year-to-year variability of leaf colouring in European beech and oak (
Fagus sylvatica L.,
Quercus petraea (Matt.) Liebl. and
Quercus robur L.). We postulate colouring to be the outcome of a one-way process triggered by photoperiod and progressing through a photoperiod-sensitive cold-degree day summation procedure. Observations were pooled according to genus for the fitting and ensuing validation procedures. Parameters of the model suggest that colouring processes start earlier, and are sensitive to higher temperatures for
Quercus than for
Fagus. Errors associated with the modelled predictions are up to 13.0 days in
Fagus and 10.3 days in
Quercus, which are significantly lower than errors associated with (1) the overall mean (null model) or (2) previously published modelling frameworks. When averaged on a site basis, model predictions reproduced spatial variability of leaf colouring over the French territory with good efficiency (modelling efficiencies: 0.44 for
Fagus, 0.45 for
Quercus). The interannual variability of leaf colouring over France was fairly reproduced (
r
2
=
0.74 for
Fagus, 0.83 for
Quercus). On that basis, we claim that the modelling framework developed herein can be efficiently integrated into more general schemes aimed at simulating matter and energy fluxes on a regional scale, and we provide a generic parameterisation of the model to be integrated into such schemes. When used in a prospective analysis, the model predicts a trend towards delay in leaf colouring of 1.4 and 1.7 days per decade in
Fagus and
Quercus, respectively, over the period of 1951–2099 in France.
•Natural antibodies (NAb) binding not-self antigens in kid serum are shown.•The synthetic hapten 2,4,6-trinitrophenyl (TNP) presents the higher immunoreactivity to Nab.•IgM-NAb and total IgM levels ...are highly correlated within each sampling time.•IgG- and IgM-NAb levels are correlated only on the 1st and the second sampling time.•Specific antibody response (SpAb) is not related to NAb and Ig levels.
Natural antibodies (NAb) are antibodies that can bind to a particular antigen without any apparent antigenic stimulation. In this paper, a careful analysis has been carried out on NAb levels in goat kid serum; possible correlations with the total immunoglobulin (tot-Ig) levels and specific antibody (SpAb) response were considered. Twenty randomly chosen kids were submitted to a first blood sampling (day 0). After 60 and 100 days, new blood samplings were carried out in the same animals. On day 0, after blood collection, all animals were immunized with a commercial vaccine; the immunization was repeated 30 days apart. Some exogenous antigens were tested to verify their immunoreactivity to NAb. Among them, the synthetic hapten 2,4,6-trinitrophenyl (TNP) conjugated with bovine serum albumin, resulted as the antigen with the higher immunoreactivity to NAb. Tot-Ig levels increased over time (p < 0.001). On the contrary, NAb levels, both IgG- and IgM-isotypes, significantly decreased during the experimental period (p < 0.001 and <0.05, respectively). Linear regression analyses showed a high correlation between IgM-NAb and tot-IgM levels (p < 0.001) at all the evaluated sampling times. However, a significant correlation between IgG-NAb and IgM-NAb was found only at the 1st (p < 0.01) and at the 2nd sampling (p < 0.05). No significant correlations were found between SpAb response and the other assessed humoral immune parameters. The obtained results are discussed in the light of the possible use of NAb assessment for the evaluation of the immune system activity in goat.
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