Lifestyles and Risk Factors Associated with Adherence to the Mediterranean Diet: A Baseline Assessment of the PREDIMED Trial

Background

The traditional Mediterranean dietary pattern (MedDiet) is associated with longevity and low rates of cardiovascular disease (CVD). However, there is little information on who is more likely to follow this food pattern.

Aim

To evaluate how different factors are associated with lower MedDiet adherence in older Spanish subjects.

Methods

We included 7305 participants (men aged 55–80 y, women 60–80 y) at high-risk of CVD recruited into the PREDIMED trial (ISRCTN35739639). Socioeconomic, anthropometric, lifestyle characteristics and CVD risk factors were recorded. A validated 14-item questionnaire was used to evaluate MedDiet adherence at baseline. Multivariate models were used to estimate odds ratios (OR) and 95% confidence intervals for lower adherence to the MedDiet (<9 points out of 14) and ascertain factors independently associated with it.

Results

Former smoking (OR = 0.87; 95% CI, 0.78–0.98), physical activity (OR for the 3^rd vs. the 1^sttertile: 0.69; 0.62–0.78), and higher educational level (OR for university vs. less than primary school: 0.54; 0.38–0.77) were associated with higher MedDiet adherence. Conversely, having a larger waist-to-height ratio (OR for 0.1 units, 1.35; 1.22–1.49), being diabetic (OR = 1.13; 1.03–1.24), being single (OR = 1.27; 1.01–1.61) or divorced or separated (OR = 1.44; 1.09–1.89), and current smoking (OR = 1.28; 1.11–1.47) were associated with lower adherence.

Conclusions

Participants with little education, a larger waist-to-height ratio, or diabetes and those who were less physically active, single, divorced or separated, or smokers were less likely to adhere to the MedDiet, an ideal model for food choices. Stronger efforts of health promotion are needed in these groups to foster adoption of the MedDiet.     

Evolution of the TIR domain-containing adaptors in humans: swinging between constraint and adaptation

Natural selection is expected to act strongly on immune system genes as hosts adapt to novel, diverse, and coevolving pathogens. Population genetic studies of host defense genes with parallel functions in model organisms have revealed distinct evolutionary histories among the different components-receptors, adaptors, and effectors-of the innate immune system. In humans, however, detailed evolutionary studies have been mainly confined to the receptors and in particular to Toll-like receptors (TLRs). By virtue of a toll/interleukin-1 receptor (TIR) domain, TLRs activate distinct signaling pathways, which are mediated by the five TIR-containing adaptors: myeloid differentiation factor-88 (MyD88), myeloid differentiation factor-88 adaptor-like protein (MAL), toll/interleukin-1 receptor domain-containing adaptor protein inducing interferon (IFN)β (TRIF), toll/interleukin-1 receptor domain-containing adaptor protein inducing IFNβ-related adaptor molecule (TRAM), and sterile α- and armadillo motif-containing protein (SARM). Here, we have examined the extent to which natural selection has affected immune adaptors in humans, using as a paradigm the TIR-containing adaptors. To do so, we characterized their levels of naturally occurring genetic variation in various human populations. We found that MyD88 and TRIF have mainly evolved under purifying selection, suggesting that their role in the early stages of signal transduction is essential and nonredundant for host survival. In addition, the adaptors have been targeted by multiple episodes of positive selection, differing in timing and spatial location. MyD88 and SARM display signatures of a selective sweep that has occurred in all humans, whereas for the other three adaptors, we detected signatures of adaptive evolution that are restricted to specific populations. Our study provides evidence that the contemporary diversity of the five TIR-containing adaptors results from the intermingling of different selective events, swinging between constraint and adaptation.     

Mitochondrial complex I impairment in leukocytes from type 2 diabetic patients

Diabetes is associated with oxidative stress. This study evaluated the rates of oxidative stress and mitochondrial impairment in type 2 diabetes patients. The study population consisted of 182 diabetic patients and 50 body-composition- and age-matched controls. We assessed anthropometric and metabolic parameters and mitochondrial function by evaluating mitochondrial oxygen (O2) consumption, reactive oxygen species (ROS) production, glutathione (GSH) levels, GSH/GSSG ratio, mitochondrial membrane potential, and mitochondrial complex I activity in polymorphonuclear cells from diabetes type 2 patients. We found an increase in waist circumference and augmented serum levels of triglycerides, proinflammatory cytokines (IL-6 and TNF-α), homocysteine, glycated hemoglobin, ultrasensitive C-reactive protein, glucose, insulin, and homeostasis model assessment of insulin resistance score in diabetic patients versus controls. There was an impairment of mitochondrial function in diabetic patients, evidenced by a decrease in mitochondrial O2 consumption, an increase in ROS production, decreased GSH/GSSG ratio, a drop in GSH levels, and an undermining of the mitochondrial membrane potential. Furthermore, an impairment of mitochondrial complex I was detected. This study supports the hypothesis of an association of type 2 diabetes and the rate of impaired mitochondrial function. We also propose that one of the targets of oxidative stress responsible for diabetes is mitochondrial complex I.     

Additional criterion for the determination of the handedness of 21 helices in crystals of bile acids: Crystal structure of a tert‐butylphenyl derivative of cholic acid

[3β,5β,7α,12α]‐3‐(4‐t‐Butylbenzoilamine)‐7,12‐dihydroxycholan‐24‐oic acid was synthesized and recrystallized from chlorobenzene and acetone. Orthorhombic P2₁2₁2₁ and monoclinic P2₁ crystals were obtained, respectively, and both crystals include solvent and water molecules with a 1:1:1 stoichiometry. In the second case, there are two nonequivalent molecules of the steroid in the unit cell. In both crystals, a crossing structure results for the molecular packing, stabilized by hydrogen bonds between the steroid molecules. In the second crystal, water links steroid molecules of the same type, which are not directly connected through hydrogen bonds. The steroid molecules define helicoidal assemblies along 2₁ screw axes. The handedness in the crystal in chlorobenzene is unambiguously defined by following the criterion proposed by Miyata et al., as the steroids are in a belly‐to‐belly disposition around the axis. This motif does not appear in the crystal in acetone, and other criterion is required. On the basis of the fact that a staircase and its banister have the same handedness and using the crystal in chlorobenzene as reference, the additional criterion has been established. According to it, in the absence of a belly‐to‐belly orientation, the handedness must be defined by keeping the bile acid with its right side oriented toward the axis. Pitch angles of the helices and tilt angles of the molecules are also determined. Chirality, 2011. © 2011 Wiley‐Liss, Inc.     

Seasonal changes of freshwater ammonia-oxidizing archaeal assemblages and nitrogen species in oligotrophic alpine lakes

The annual changes in the composition and abundance of ammonia-oxidizing archaea (AOA) were analyzed monthly in surface waters of three high mountain lakes within the Limnological Observatory of the Pyrenees (LOOP; northeast Spain) using both 16S rRNA and functional (ammonia monooxygenase gene, amoA) gene sequencing as well as quantitative PCR amplification. The set of biological data was related to changes in nitrogen species and to other relevant environmental variables. The whole archaeal assemblage was dominated by phylotypes closely related to the crenarchaeal 1.1a group (58% ± 18% of total 16S rRNA gene sequences), and consistent structural changes were detected during the study. Water temperature was the environmental variable that better explained spring, summer, and winter (ice-covered lakes) archaeal assemblage structure. The amoA gene was detected year round, and seasonal changes in amoA gene composition were well correlated with changes in the archaeal 16S rRNA gene pool. In addition, copy numbers of both the specific 1.1a group 16 rRNA and archaeal amoA genes were well correlated, suggesting that most freshwater 1.1a Crenarchaeota had the potential to carry out ammonia oxidation. Seasonal changes in the diversity and abundance of AOA (i.e., amoA) were better explained by temporal changes in ammonium, the substrate for nitrification, and mostly nitrite, the product of ammonia oxidation. Lacustrine amoA gene sequences grouped in coherent freshwater phylogenetic clusters, suggesting that freshwater habitats harbor typical amoA-containing ecotypes, which is different from soils and seas. We observed within the freshwater amoA gene sequence pool a high genetic divergence (translating to up to 32% amino acid divergence) between the spring and the remaining AOA assemblages. This suggests that different AOA ecotypes are adapted to different temporal ecological niches in these lakes.     

New thiopyrazolo[3,4-d]pyrimidine derivatives as anti-mycobacterial agents

The multiple parallel synthesis of a series of N,S-bis-alkylated thiopyrazolo[3,4-d]pyrimidines, based on sequential S- then N-alkylation, is reported. These compounds showed significant anti-mycobacterial activity (MICs down to 2mug/ml) and their potential as significant drug-like leads is substantiated through cytotoxicity evaluation and in silico profiling.     

Nonoverlapping functions of the Polycomb group Cbx family of proteins in embryonic stem cells

Polycomb group proteins are essential regulators of cell fate decisions during embryogenesis. In mammals, at least five different Cbx proteins (Cbx2, Cbx4, Cbx6, Cbx7, and Cbx8) are known to associate with the core Polycomb repressive complex 1 (PRC1). Here we show that pluripotency and differentiation of mouse embryonic stem cells (ESCs) is regulated by different Cbx-associated PRC1 complexes with unique functions. Maintenance of pluripotency primarily depends on Cbx7, while lineage commitment is orchestrated by Cbx2 and Cbx4. At the molecular level, we have uncovered a Polycomb autoregulatory loop in which Cbx7 represses the expression of prodifferentiation Cbx proteins, thereby maintaining the pluripotent state. We additionally show that the occupancy of Cbx7 on promoters is completely dependent on PRC2 activity but only partially dependent on a functional PRC1 complex. Thus, Cbx proteins confer distinct target selectivity to the PRC1 complex, achieving a balance between the self-renewal and the differentiation of ESCs.