To evaluate whether women with anaemia or high haemoglobin (Hb) in early pregnancy would be at higher risk of miscarriage, this population-based cohort study involved 9453 women whose pregnancies ...were monitored at primary care centres between 2007 and 2012. The computerised clinical histories were used to collect: Hb measurements (up to 14 weeks of gestation), miscarriage before or by 24 weeks of gestation, and other maternal characteristics. The relation between anaemia (Hb < 110 g/L), normal Hb (110–140 g/L, reference), and high Hb concentrations (≥140 g/L) with miscarriage were expressed as adjusted OR with 95%CI. Restricted cubic spline models were applied to evaluate the dose-response relationships. A total of 520 (5.5%) women were recorded as having a miscarriage. The rate of miscarriage in anaemia, normal Hb, and high Hb concentrations was 8.4%, 5.1%, and 10.2%, respectively. Compared with women with normal Hb at the first trimester, the multivariable-adjusted OR for miscarriage was 2.11 (95%CI, 1.38–3.21) for women with anaemia and 1.83 (95%CI, 1.29–2.58) for women with high Hb. Hb concentrations showed a U-shaped association with miscarriage, with the lowest incidence among women with Hb of 120–130 g/L. These data highlight the importance of considering anaemia and high Hb levels in early pregnancy as harmful indicators for miscarriage.
Purpose
Cardiovascular disease remains the global leading cause of death. We evaluated at baseline the association between the adherence to eight a priori high-quality dietary scores and the ...prevalence of individual and clustered cardiovascular risk factors (CVRF) in the PREDIMED-Plus cohort.
Methods
All PREDIMED-Plus participants (6874 men and women aged 55–75 years, with overweight/obesity and metabolic syndrome) were assessed. The prevalence of 4 CVRF (hypertension, obesity, diabetes, and dyslipidaemia), using standard diagnoses criteria, were considered as outcomes. The adherence to eight a priori-defined dietary indexes was calculated. Multivariable models were fitted to estimate differences in mean values of factors and prevalence ratios for individual and clustered CVRF.
Results
Highest conformity to any dietary pattern did not show inverse associations with hypertension. The modified Mediterranean Diet Score (PR = 0.95; 95% CI 0.90–0.99), Mediterranean Diet Adherence Score (MEDAS) (PR = 0.94; 95% CI 0.89–0.98), the pro-vegetarian dietary pattern (PR = 0.95; 95% CI 0.90–0.99) and the Alternate Healthy Eating Index 2010 (PR = 0.92; 95% CI 0.87–0.96) were inversely associated with prevalence of obesity. We identified significant inverse trend among participants who better adhered to the MEDAS and the Prime Diet Quality Score (PDQS) in the mean number of CVRF across categories of adherence. Better adherence to several high-quality dietary indexes was associated with better blood lipid profiles and anthropometric measures.
Conclusions
Highest adherence to dietary quality indexes, especially Mediterranean-style and PDQS scores, showed marginal associations with lower prevalence of individual and clustered CVRF among elderly adults with metabolic syndrome at high risk of cardiovascular disease
Several anthropometric measurements have been associated with cardiovascular disease, type-2 diabetes mellitus and other cardiovascular risk conditions, such as hypertension or metabolic syndrome. ...Waist-to-height-ratio has been proposed as a useful tool for assessing abdominal obesity, correcting other measurements for the height of the individual. We compared the ability of several anthropometric measurements to predict the presence of type-2 diabetes, hyperglycemia, hypertension, atherogenic dyslipidemia or metabolic syndrome.
In our cross-sectional analyses we included 7447 Spanish individuals at high cardiovascular risk, men aged 55-80 years and women aged 60-80 years, from the PREDIMED study. Logistic regression models were fitted to evaluate the odds ratio of presenting each cardiovascular risk factor according to various anthropometric measures. The areas under the receiver-operating characteristic curve (AUC) were used to compare the predictive ability of these measurements.
In this relatively homogeneous cohort with 48.6% of type-2 diabetic individuals, the great majority of the studied anthropometric parameters were significantly and positively associated with the cardiovascular risk factors. No association was found between BMI and body weight and diabetes mellitus. The AUCs for the waist-to-height ratio and waist circumference were significantly higher than the AUCs for BMI or weight for type-2 diabetes, hyperglycemia, atherogenic dyslipidemia and metabolic syndrome. Conversely, BMI was the strongest predictor of hypertension.
We concluded that measures of abdominal obesity showed higher discriminative ability for diabetes mellitus, high fasting plasma glucose, atherogenic dyslipidemia and metabolic syndrome than BMI or weight in a large cohort of elderly Mediterranean individuals at high cardiovascular risk. No significant differences were found between the predictive abilities of waist-to-height ratio and waist circumference on the metabolic disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Circadian rhythms regulate key biological processes influencing metabolic pathways. Disregulation is associated with type 2 diabetes (T2D) and cardiovascular diseases (CVD). Circadian rhythms are ...generated by a transcriptional autoregulatory feedback loop involving core clock genes. CLOCK (circadian locomotor output cycles protein kaput), one of those core genes, is known to regulate glucose metabolism in rodent models. Cross-sectional studies in humans have reported associations between this locus and obesity, plasma glucose, hypertension and T2D prevalence, supporting its role in cardiovascular risk. However, no longitudinal study has investigated the association between CLOCK gene variation and T2D or CVD incidence. Moreover, although in a previous work we detected a gene-diet interaction between the CLOCK-rs4580704 (C > G) single nucleotide polymorphism (SNP) and monounsaturated (MUFA) intake on insulin resistance, no interventional study has analyzed gene-diet interactions on T2D or CVD outcomes.
We analyzed the association between the CLOCK-rs4580704 SNP and incidence of T2D and CVD longitudinally in 7098 PREDIMED trial (ISRCTN35739639) participants after a median 4.8-year follow-up. We also examined modulation by Mediterranean diet (MedDiet) intervention (high in MUFA) on these associations.
We observed a significant association between the CLOCK-rs4580704 SNP and T2D incidence in n = 3671 non-T2D PREDIMED participants, with variant allele (G) carriers showing decreased incidence (dominant model) compared with CC homozygotes (HR: 0.69; 95 % CI 0.54-0.87; P = 0.002). This protection was more significant in the MedDiet intervention group (HR: 0.58; 95 % CI 0.43-0.78; P < 0.001) than in the control group (HR: 0.95; 95 % CI 0.63-1.44; P = 0.818). Moreover, we detected a statistically significant interaction (P = 0.018) between CLOCK-rs4580704 SNP and T2D status on stroke. Thus, only in T2D subjects was CLOCK-rs4580704 SNP associated with stroke risk, G-carriers having decreased risk (HR: 0.61; 95 % CI 0.40-0.94; P = 0.024 versus CC) in the multivariable-adjusted model.
In agreement with our previous results showing a protective effect of the G-allele against hyperglycemia, we extended our findings by reporting a novel association with lower T2D incidence and also suggesting a dietary modulation. Moreover, we report for the first time an association between a CLOCK polymorphism and stroke in T2D subjects, suggesting that core clock genes may significantly contribute to increased CVD risk in T2D.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Breast cancer (BC) is the leading cause of cancer-related death among women and the most commonly diagnosed cancer worldwide. Although in recent years large-scale efforts have focused on identifying ...new therapeutic targets, a better understanding of BC molecular processes is required. Here we focused on elucidating the molecular hallmarks of BC heterogeneity and the oncogenic mutations involved in precision medicine that remains poorly defined. To fill this gap, we established an OncoOmics strategy that consists of analyzing genomic alterations, signaling pathways, protein-protein interactome network, protein expression, dependency maps in cell lines and patient-derived xenografts in 230 previously prioritized genes to reveal essential genes in breast cancer. As results, the OncoOmics BC essential genes were rationally filtered to 140. mRNA up-regulation was the most prevalent genomic alteration. The most altered signaling pathways were associated with basal-like and Her2-enriched molecular subtypes. RAC1, AKT1, CCND1, PIK3CA, ERBB2, CDH1, MAPK14, TP53, MAPK1, SRC, RAC3, BCL2, CTNNB1, EGFR, CDK2, GRB2, MED1 and GATA3 were essential genes in at least three OncoOmics approaches. Drugs with the highest amount of clinical trials in phases 3 and 4 were paclitaxel, docetaxel, trastuzumab, tamoxifen and doxorubicin. Lastly, we collected ~3,500 somatic and germline oncogenic variants associated with 50 essential genes, which in turn had therapeutic connectivity with 73 drugs. In conclusion, the OncoOmics strategy reveals essential genes capable of accelerating the development of targeted therapies for precision oncology.
Breast cancer (BC) is a heterogeneous disease where genomic alterations, protein expression deregulation, signaling pathway alterations, hormone disruption, ethnicity and environmental determinants ...are involved. Due to the complexity of BC, the prediction of proteins involved in this disease is a trending topic in drug design. This work is proposing accurate prediction classifier for BC proteins using six sets of protein sequence descriptors and 13 machine-learning methods. After using a univariate feature selection for the mix of five descriptor families, the best classifier was obtained using multilayer perceptron method (artificial neural network) and 300 features. The performance of the model is demonstrated by the area under the receiver operating characteristics (AUROC) of 0.980 ± 0.0037, and accuracy of 0.936 ± 0.0056 (3-fold cross-validation). Regarding the prediction of 4,504 cancer-associated proteins using this model, the best ranked cancer immunotherapy proteins related to BC were RPS27, SUPT4H1, CLPSL2, POLR2K, RPL38, AKT3, CDK3, RPS20, RASL11A and UBTD1; the best ranked metastasis driver proteins related to BC were S100A9, DDA1, TXN, PRNP, RPS27, S100A14, S100A7, MAPK1, AGR3 and NDUFA13; and the best ranked RNA-binding proteins related to BC were S100A9, TXN, RPS27L, RPS27, RPS27A, RPL38, MRPL54, PPAN, RPS20 and CSRP1. This powerful model predicts several BC-related proteins that should be deeply studied to find new biomarkers and better therapeutic targets. Scripts can be downloaded at https://github.com/muntisa/neural-networks-for-breast-cancer-proteins.
The current study developed and tested a mediation model that accounts for the procedural justice in the relationship between the perception of job insecurity and affect. We used a sample of 681 ...workers, from four private enterprises in the retail industry in Chile, who survived an organizational downsizing process. The hypotheses were tested by using structural equation modeling (SEM). The results indicated that the perception of job insecurity and employees' negative affects was partially mediated by procedural justice. However, the relationship between job insecurity and employees' positive affects was totally mediated by procedural justice. Therefore, such results suggest that it is important during a downsizing process for companies to implement actions to enhance job security in order to develop adequate affect among survivors. Furthermore, it is also seemingly crucial that justice should be an important issue in the downsizing process, and that the company should develop actions that reflect the perception of procedural justice throughout the process. Thus, this research provides evidence that it is useful to simultaneously consider procedural justice and stress reactions in a downsizing process, since neither are independent variables.
Short dietary assessment tools can be useful to estimate food intake and diet quality in large-scale epidemiological studies with time constraints.
To determine the concurrent validity of the 17-item ...energy-restricted Mediterranean Adherence Screener (er-MEDAS) used in the PREDIMED (PREvención con DIeta MEDiterránea)-Plus trial and to analyse its capacity to detect 1-year changes in diet and cardiometabolic risk factors.
Validation study nested in the PREDIMED-Plus (n = 6760, 55–75 years). Dietary data were collected by the 17-item er-MEDAS and a 143-item validated semiquantitative food frequency questionnaire (FFQ) at baseline and after 1-year intervention. Cardiometabolic risk markers were measured at both time points. A Mediterranean diet (MedDiet) score was derived from both instruments. Concurrent validity was evaluated by Pearson and intra-class correlation coefficients (ICC) and Bland and Altman limits of agreement. Construct validity was evaluated by assessing 1-year changes in FFQ-reported dietary intake and cardiometabolic profile changes in relation to changes in er-MEDAS.
A moderate to good correlation between the MedDiet score calculated by both measurement instruments was found: r = 0.61 and ICC = 0.60 (both p < 0.001). Agreement of each of the er-MEDAS items ranged from 55.4% to 85.0% with a moderate mean concordance (kappa = 0.41). Between baseline and 1-year follow-up, energy intake measured by the FFQ decreased by 242 kcal, while Mediterranean food consumption increased in participants with the highest increase in the er-MEDAS MedDiet score. An increase in the er-MEDAS MedDiet score ratings was associated with a decrease in BMI, waist circumference, triglycerides, fasting glucose, diastolic blood pressure, and triglycerides/HDL-cholesterol ratio (p < 0.001 for all), and with an increase in HDL-cholesterol (p = 0.006).
The er-MEDAS shows a modest to good concurrent validity compared with FFQ data. It shows acceptable construct validity, as a greater er-MEDAS score was associated with more favourable dietary and cardiometabolic profiles over time.
ISRCTN89898870; registration date, 24 July 2014. https://www.isrctn.com/ISRCTN89898870.
IMPORTANCE: High-quality dietary patterns may help prevent chronic disease, but limited data exist from randomized trials about the effects of nutritional and behavioral interventions on dietary ...changes. OBJECTIVE: To assess the effect of a nutritional and physical activity education program on dietary quality. DESIGN, SETTING, AND PARTICIPANTS: Preliminary exploratory interim analysis of an ongoing randomized trial. In 23 research centers in Spain, 6874 men and women aged 55 to 75 years with metabolic syndrome and no cardiovascular disease were enrolled in the trial between September 2013 and December 2016, with final data collection in March 2019. INTERVENTIONS: Participants were randomized to an intervention group that encouraged an energy-reduced Mediterranean diet, promoted physical activity, and provided behavioral support (n = 3406) or to a control group that encouraged an energy-unrestricted Mediterranean diet (n = 3468). All participants received allotments of extra-virgin olive oil (1 L/mo) and nuts (125 g/mo) for free. MAIN OUTCOMES AND MEASURES: The primary outcome was 12-month change in adherence based on the energy-reduced Mediterranean diet (er-MedDiet) score (range, 0-17; higher scores indicate greater adherence; minimal clinically important difference, 1 point). RESULTS: Among 6874 randomized participants (mean SD age, 65.0 4.9 years; 3406 52% men), 6583 (96%) completed the 12-month follow-up and were included in the main analysis. The mean (SD) er-MedDiet score was 8.5 (2.6) at baseline and 13.2 (2.7) at 12 months in the intervention group (increase, 4.7 95% CI, 4.6-4.8) and 8.6 (2.7) at baseline and 11.1 (2.8) at 12 months in the control group (increase, 2.5 95% CI, 2.3-2.6) (between-group difference, 2.2 95% CI, 2.1-2.4; P < .001). CONCLUSIONS AND RELEVANCE: In this preliminary analysis of an ongoing trial, an intervention that encouraged an energy-reduced Mediterranean diet and physical activity, compared with advice to follow an energy-unrestricted Mediterranean diet, resulted in a significantly greater increase in diet adherence after 12 months. Further evaluation of long-term cardiovascular effects is needed. TRIAL REGISTRATION: isrctn.com Identifier: ISRCTN89898870
El presente artículo analiza el proceso de la adaptación partidaria de las Fuerzas Armadas Revolucionarias de Colombia —Ejército del Pueblo, FARC-EP, basándose en la concepción de Sidney Tarrow de la ...estructura de oportunidad política-EOP—. Pretende dar respuesta a la pregunta de cuáles fueron los distintos factores de la EOP presentes en el contexto político y social colombiano y cómo estos influyeron en las FARC-EP para abandonar las armas e integrarse en el sistema político colombiano como un nuevo partido político con presencia en las instituciones democráticas, dejando atrás las armas y cambiándolas por las palabras. Metodológicamente, se realiza un análisis documental desde la perspectiva teórica del concepto de la estructura de oportunidad política de Tarrow recogiendo los principales factores influyentes en el concepto de la EOP. Se concluye que las FARC-EP supieron aprovechar las distintas oportunidades abiertas en la EOP a través de un aumento de presión sobre diferentes sectores para conseguir los cambios deseados y culminar así con la aprobación de los acuerdos de paz de La Habana y su adaptación a partido político
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