Circulating vitamin D levels and colorectal cancer risk: a meta-analysis and systematic review of case-control and prospective cohort studies

The associations between circulating vitamin D concentrations and total and site-specific colorectal cancer (CRC) incidence have been examined in several epidemiological studies with overall inconclusive findings. The aim of this systematic review and meta-analysis of both case-control and prospective cohort studies was to evaluate the association between CRC and circulating levels of vitamin D. The main exposure and outcome were circulating total 25(OH)D and CRC, respectively, in the overall population (i.e., all subjects). Two reviewers, working independently, screened all the literature available to identify studies that met the inclusion criteria (e.g., case-control or prospective cohort studies, published in English, and excluding non-original papers). Data were pooled by the generic inverse variance method using a random or fixed effect model, as approriate. Heterogeneity was identified using the Cochran's Q-test and quantified by the I2 statistic. Results were stratified by study design, sex, and metabolite of vitamin D. Sensitivity and subgroup analyses were also performed. A total of 28 original studies were included for the quantitative meta-analysis. Meta-analyses comparing the highest vs lowest categories, showed a 39% lower risk between levels of total 25(OH)D and CRC risk (OR (95% CI): 0.61 (0.52; 0.71); 11 studies) in case-control studies; whereas a 20% reduced CRC risk in prospective cohort studies (HR (95% CI): 0.80 (0.66; 0.97); 6 studies). Results in women mirrored main results, whereas results in men were non-significant in both analyses. Our findings support an inverse association between circulating vitamin D levels and CRC risk

Characterization of new regulatory elements within the Drosophila bithorax complex

The homeotic Abdominal-B (Abd-B) gene expression depends on a modular cis-regulatory region divided into discrete functional domains (iab) that control the expression of the gene in a particular segment of the fly. These domains contain regulatory elements implicated in both initiation and maintenance of homeotic gene expression and elements that separate the different domains. In this paper we have performed an extensive analysis of the iab-6 regulatory region, which regulates Abd-B expression at abdominal segment A6 (PS11), and we have characterized two new polycomb response elements (PREs) within this domain. We report that PREs at Abd-B cis-regulatory domains present a particular chromatin structure which is nuclease accessible all along Drosophila development and both in active and repressed states. We also show that one of these regions contains a dCTCF and CP190 dependent activity in transgenic enhancer-blocking assays, suggesting that it corresponds to the Fab-6 boundary element of the Drosophila bithorax complex

dSAP18 and dHDAC1 contribute to the functional regulation of the Drosophila Fab-7 element

It was described earlier that the Drosophila GAGA factor [Trithorax-like (Trl)] interacts with dSAP18, which, in mammals, was reported to be a component of the Sin3–HDAC co-repressor complex. GAGA–dSAP18 interaction was proposed to contribute to the functional regulation of the bithorax complex (BX-C). Here, we show that mutant alleles of Trl, dsap18 and drpd3/hdac1 enhance A6-to-A5 transformation indicating a contribution to the regulation of Abd-B expression at A6. In A6, expression of Abd-B is driven by the iab-6 enhancer, which is insulated from iab-7 by the Fab-7 element. Here, we report that GAGA, dSAP18 and dRPD3/HDAC1 co-localize to ectopic Fab-7 sites in polytene chromosomes and that mutant Trl, dsap18 and drpd3/hdac1 alleles affect Fab-7-dependent silencing. Consistent with these findings, chromatin immunoprecipitation analysis shows that, in Drosophila embryos, the endogenous Fab-7 element is hypoacetylated at histones H3 and H4. These results indicate a contribution of GAGA, dSAP18 and dRPD3/HDAC1 to the regulation of Fab-7 function

Revisiting mortality deceleration patterns in a gamma-Gompertz-Makeham framework

We calculate life-table aging rates (LARs) for overall mortality by estimating a gamma-Gompertz-Makeham (G GM) model and taking advantage of LAR’s parametric representation by Vaupel and Zhang [34]. For selected HMD countries, we study how the evolution of estimated LAR patterns could explain observed 1) longevity dynamics, and 2) mortality improvement or deterioration at different ages. Surprisingly, the age of mortality deceleration x showed almost no correlation with a number of longevity measures apart from e0. In addition, as mortality concentrates at older ages with time, its characteristic bell-shaped pattern becomes more pronounced. Moreover, in a GGM framework, we identify the impact of senescent mortality on shape of the rate of population aging. We also find evidence for a strong relationship between x and the statistically significant curvilinear changes in the evolution of e0 over time. Finally, model-based LARs appear to be consistent with point b) of the “heterogeneity hypothesis” [12]: mortality deceleration, due to selection effects, should shift to older ages as the level of total adult mortality declines

First measurement of the CP-violating phase in B0s→J/ψ( → e+e−)ϕ decays

A flavour-tagged time-dependent angular analysis of B0 s → J/ψφ decays is presented where the J/ψ meson is reconstructed through its decay to an e +e − pair. The analysis uses a sample of pp collision data recorded with the LHCb experiment at centre-of-mass energies of 7 and 8 TeV, corresponding to an integrated luminosity of 3 fb−1 . The CP-violating phase and lifetime parameters of the B0 s system are measured to be φs = 0.00 ± 0.28 ± 0.05 rad, ∆Γs = 0.115 ± 0.045 ± 0.011 ps−1 and Γs = 0.608 ± 0.018 ± 0.011 ps−1 where the first uncertainty is statistical and the second systematic. This is the first time that CP-violating parameters are measured in the B0 s → J/ψφ decay with an e +e − pair in the final state. The results are consistent with previous measurements in other channels and with the Standard Model predictions

Characterization of the Interaction between the Cohesin Subunits Rad21 and SA1/2

The cohesin complex is responsible for the fidelity of chromosomal segregation during mitosis. It consists of four core subunits, namely Rad21/Mcd1/Scc1, Smc1, Smc3, and one of the yeast Scc3 orthologs SA1 or SA2. Sister chromatid cohesion is generated during DNA replication and maintained until the onset of anaphase. Among the many proposed models of the cohesin complex, the ﾒcoreﾒ cohesin subunits Smc1, Smc3, and Rad21 are almost universally displayed as tripartite ring. However, other than its supportive role in the cohesin ring, little is known about the fourth core subunit SA1/SA2. To gain deeper insight into the function of SA1/SA2 in the cohesin complex, we have mapped the interactive regions of SA2 and Rad21 in vitro and ex vivo. Whereas SA2 interacts with Rad21 through a broad region (301ﾖ750 aa), Rad21 binds to SA proteins through two SA-binding motifs on Rad21, namely N-terminal (NT) and middle part (MP) SA-binding motif, located At 60-81 aa of the N-terminus and 383ﾖ392 aa of the MP of Rad21, respectively. The MP SA-binding motif is a 10 amino acid, a-helical motif. Deletion of these 10 amino acids or mutation of three conserved amino acids (L385, F389, and T390) in this ahelical motif significantly hinders Rad21 from physically interacting with SA1/2. Besides the MP SA-binding motif, the NT SAbinding motif is also important for SA1/2 interaction. Although mutations on both SA-binding motifs disrupt Rad21-SA1/2 interaction, they had no apparent effect on the Smc1-Smc3-Rad21 interaction. However, the Rad21-Rad21 dimerization was reduced by the mutations, indicating potential involvement of the two SA-binding motifs in the formation of the two-ring handcuff for chromosomal cohesion. Furthermore, mutant Rad21 proteins failed to significantly rescue precocious chromosome separation caused by depletion of endogenous Rad21 in mitotic cells, further indicating the physiological significance of the two SA-binding motifs of Rad21

Cause-of-Death Contributions to Educational Inequalities in Mortality in Austria between 1981/1982 and 1991/1992: Les contributions des causes de décès aux inégalités de mortalité par niveau d’éducation en Autriche entre 1981/1982 et 1991/1992

This article uses census records and deaths records to analyze trends in educational inequalities in mortality for Austrian women and men aged 35–64 years between 1981/1982 and 1991/1992. We find an increasing gradient in mortality by education for circulatory diseases and especially ischaemic heart disease. Respiratory diseases and, in addition for women, cancers showed the opposite trend. Using decomposition analysis, we give evidence that in many cases changes in the age-structure within the 10-year interval had a bigger effect than direct improvements in mortality on the analyzed subpopulations

Extra virgin olive oil consumption reduces the risk of osteoporotic fractures in the PREDIMED trial

BACKGROUND & AIMS: The incidence of osteoporotic fractures is lower in countries in the Mediterranean basin. Virgin olive oil, a key component of the Mediterranean Diet (MDiet), with recognised beneficial effects on metabolism and cardiovascular health, may decrease the risk of osteoporotic fractures. The aim to this study was to explore the effect of chronic consumption of total olive oil and its varieties on the risk of osteoporosis-related fractures in a middle-aged and elderly Mediterranean population. METHODS: We included all participants (n = 870) recruited in the Reus (Spain) centre of the PREvención con DIeta MEDiterránea (PREDIMED) trial. Individuals, aged 55-80 years at high cardiovascular risk, were randomized to a MedDiet supplemented with extra-virgin olive oil, a MedDiet supplemented with nuts, or a low-fat diet. The present analysis was an observational cohort study nested in the trial. A validated food frequency questionnaire was used to assess dietary habits and olive oil consumption. Information on total osteoporotic fractures was obtained from a systematic review of medical records. The association between yearly repeated measurements of olive oil consumption and fracture risk was assessed by multivariate Cox proportional hazards. RESULTS: We documented 114 incident cases of osteoporosis-related fractures during a median follow-up of 8.9 years. Treatment allocation had no effect on fracture risk. Participants in the highest tertile of extra-virgin olive oil consumption had a 51% lower risk of fractures (HR:0.49; 95% CI:0.29-0.81. P for trend = 0.004) compared to those in the lowest tertile after adjusting for potential confounders. Total and common olive oil consumption was not associated with fracture risk. CONCLUSIONS: Higher consumption of extra-virgin olive oil is associated with a lower risk of osteoporosis-related fractures in middle-aged and elderly Mediterranean population at high cardiovascular risk

Plasma metabolites associated with homeostatic model assessment of insulin resistance: metabolite-model design and external validation

Different plasma metabolites have been related to insulin resistance (IR). However, there is a lack of metabolite models predicting IR with external validation. The aim of this study is to identify a multi-metabolite model associated to the homeostatic model assessment (HOMA)-IR values. We performed a cross-sectional metabolomics analysis of samples collected from overweight and obese subjects from two independent studies. The training step was performed in 236 subjects from the SATIN study and validated in 102 subjects from the GLYNDIET study. Plasma metabolomics profile was analyzed using three different approaches: GC/quadrupole-TOF, LC/quadrupole-TOF, and nuclear magnetic resonance (NMR). Associations between metabolites and HOMA-IR were assessed using elastic net regression analysis with a leave-one-out cross validation (CV) and 100 CV runs. HOMA-IR was analyzed both as linear and categorical (median or lower versus higher than the median). Receiver operating characteristic curves were constructed based on metabolites’ weighted models. A set of 30 metabolites discriminating extremes of HOMA-IR were consistently selected. These metabolites comprised some amino acids, lipid species and different organic acids. The area under the curve (AUC) for the discrimination between HOMA-IR extreme categories was 0.82 (95% CI: 0.74–0.90), based on the multi-metabolite model weighted with the regression coefficients of metabolites in the validation dataset. We identified a set of metabolites discriminating between extremes of HOMA-IR and able to predict HOMA-IR with high accuracy

Limitations and potentials of dual-purpose cow herds in Central Coastal Veracruz, Mexico

Feed chemical and kinetic composition and animal performance information was used to evaluate productivity limitations and potentials of dual-purpose member herds of the Genesis farmer organization of central coastal Veracruz, Mexico. The Cornell Net Carbohydrate and Protein System model (Version 6.0) was systematically applied to specific groups of cows in structured simulations to establish probable input–output relationships for typical management, and to estimate probable outcomes from alternative management based on forage-based dietary improvements. Key herd vulnerabilities were pinpointed: chronic energy deficits among dry cows of all ages in late gestation and impeded growth for immature cows. Regardless of the forage season of calving, most cows, if not all, incur energy deficits in the final trimester of gestation; thus reducing the pool of tissue energy and constraining milking performance. Under typical management, cows are smaller and underweight for their age, which limits feed intake capacity, milk production and the probability of early postpartum return to ovarian cyclicity. The substitution of good-quality harvested forage for grazing increased predicted yields by about one-third over typical scenarios for underweight cows. When diets from first parturition properly supported growth and tissue repletion, milk production in second and third lactations was predicted to improve about 60%. Judiciously supplemented diets based on good quality grass and legume forages from first calving were predicted to further increase productivity by about 80% across a three-lactation cow lifetime. These dual-purpose herd owners have large incentives to increase sales income by implementing nutritional strategies like those considered in this study