Abstract Background Diet is a key modifiable risk for many chronic diseases, but it remains unclear whether dietary patterns from one study sample are generalizable to other independent populations. ...Objective The primary objective of this study was to assess whether data-driven dietary patterns from one study sample are applicable to other populations. The secondary objective was to assess the validity of two criteria of pattern similarity. Methods Six dietary patterns—Western (n=3), Mediterranean, Prudent, and Healthy— from three published studies on breast cancer were reconstructed in a case-control study of 973 breast cancer patients and 973 controls. Three more internal patterns (Western, Prudent, and Mediterranean) were derived from this case-control study’s own data. Statistical analysis Applicability was assessed by comparing the six reconstructed patterns with the three internal dietary patterns, using the congruence coefficient (CC) between pattern loadings. In cases where any pair met either of two commonly used criteria for declaring patterns similar (CC ≥0.85 or a statistically significant P <0.05 Pearson correlation), then the true similarity of those two dietary patterns was double-checked by comparing their associations to risk for breast cancer, to assess whether those two criteria of similarity are actually reliable. Results Five of the six reconstructed dietary patterns showed high congruence (CC >0.9) to their corresponding dietary pattern derived from the case-control study’s data. Similar associations with risk for breast cancer were found in all pairs of dietary patterns that had high CC but not in all pairs of dietary patterns with statistically significant correlations. Conclusions Similar dietary patterns can be found in independent samples. The P value of a correlation coefficient is less reliable than the CC as a criterion for declaring two dietary patterns similar. This study shows that diet scores based on a particular study are generalizable to other populations.
Sex-Specific Protective Effects of APOE ε2 on Cognitive Performance Lamonja-Vicente, Noemí; Dacosta-Aguayo, Rosalia; López-Olóriz, Jorge ...
The journals of gerontology. Series A, Biological sciences and medical sciences,
2021-Jan-01, 2021-01-01, 20210101, Letnik:
76, Številka:
1
Journal Article
Recenzirano
Apolipoprotein E (APOE) has an important role in the multiple trajectories of cognitive aging. However, environmental variables and other genes mediate the impact of APOE on cognition. Our main ...objective was to analyze the effect of APOE genotype on cognition and its interactions and relationships with sex, age, lipid profile, C-reactive protein, and Brain-derived neurotrophic factor (BDNF) genotype in a sample of 648 healthy participants over 50 years of age with a comprehensive neuropsychological assessment. Our results showed that APOE ε2 carriers performed better in the Verbal Memory (p = .002) and Fluency Domains (p = .001). When we studied the effect of sex, we observed that the beneficial effect of APOE ε2 on the normalized values of these cognitive domains occurred only in females (β = 0.735; 95% confidence interval, 0.396-1.074; p = 3.167·10-5 and β = 0.568; 95% confidence interval, 0.276-0.861; p = 1.853·10-4, respectively). Similarly, the sex-specific effects of APOE ε2 were further observed on lipidic and inflammation biomarkers. In the whole sample, APOE ε2 carriers showed significantly lower levels of total cholesterol, low-density lipoprotein cholesterol, and C-reactive protein. These differences were found only among females. Furthermore, total cholesterol and low-density lipoprotein cholesterol mediated the protective effect of APOE ε2 on cognition in the whole sample and total cholesterol in females, providing candidate physiological mechanisms for the observed genetic effects. Our results show that the neuroprotective role of APOE ε2 in cognition varies with sex and that the lipidic profile partially mediates this protection. Age-related cognitive and functional decline is a continuous biological process with different cognitive trajectories (1). Complex interactions between heritability, environmental influence, and cognitive functions in aging have been highlighted (2). In particular, genetic differences explain around 15%-25% of the variance in life expectancy (3). Therefore, the identification of susceptibility genes and their biological effects on cognitive aging is required to establish interindividual differences in this process and promote early personalized interventions to delay cognitive decline and minimize the financial burden of aging in the health care system.
Summary Background We aimed to compare the additional benefit of gemcitabine when combined with vinorelbine above that of standard vinorelbine treatment in patients with metastatic breast cancer. ...Methods In this phase III, multicentre, open-label, randomised study, 252 women with locally recurrent and metastatic breast cancer who had been pretreated with anthracyclines and taxanes were randomly assigned single-agent vinorelbine (30 mg/m2 , days 1 and 8) or gemcitabine plus vinorelbine (1200/30 mg/m2 , days 1 and 8). Both study treatments were administered intravenously every 21 days until disease progression, unacceptable toxic effects, or stoppage at the request of investigator or patient. The primary endpoint was median progression-free survival. Secondary objectives included assessments of response rate, disease duration, overall survival, and characterisation of the toxicity profiles of both regimens. This study is registered with ClinicalTrials.gov , number NCT00128310. Findings Between 2001 and 2005, 252 women were recruited and randomised for treatment. One of these patients was ineligible. Prognostic factors were well balanced between treatment groups (median number of metastatic sites in combination group 2 (range 0–5) and in vinorelbine group 2 (range 1–6); visceral disease in 76% and 75% of patients, respectively). Median progression-free survival was 6·0 months (95% CI 4·8–7·1) for patients given gemcitabine plus vinorelbine and 4·0 months (2·9–5·1) for those assigned vinorelbine; there was 1·9 months of difference (hazard ratio 0·66 0·50–0·88; p=0·0028). Overall survival was 15·9 months (12·6–19·1) for the gemcitabine plus vinorelbine group and 16·4 months (11·6–21·0) for the vinorelbine group; there was 0·5 months of difference (hazard ratio 1·04 0·78–1·39; p=0·8046). Objective response rates were 36% for patients assigned gemcitabine plus vinorelbine (n=45) and 26% for those assigned vinorelbine (n=33) (p=0·093). Grade 3 or 4 neutropenia was reported in 75 (61% 52–70) of the participants assigned gemcitabine plus vinorelbine, compared with 55 (44% 35–53) of those assigned vinorelbine alone (p=0·0074). Febrile neutropenia occurred in 13 (11%) of those assigned gemcitabine plus vinorelbine, and in seven (6%) of those assigned vinorelbine alone (p=0·15). Incidences of grade 3 or 4 non-haematological toxic effects were similar between the two treatment groups. Interpretation Patients with metastatic breast cancer assigned gemcitabine and vinorelbine had better progression-free survival compared with those assigned vinorelbine alone. However, this finding did not translate into a difference in overall survival. Although toxicity was manageable, patients in the combined group had more haematological toxic effects. These factors should be taken into account when deciding which chemotherapy patients should receive.
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