Obesity Indexes and Total Mortality among Elderly Subjects at High Cardiovascular Risk: The PREDIMED Study

Background

Different indexes of regional adiposity have been proposed for identifying persons at higher risk of death. Studies specifically assessing these indexes in large cohorts are scarce. It would also be interesting to know whether a dietary intervention may counterbalance the adverse effects of adiposity on mortality.

Methods

We assessed the association of four different anthropometric indexes (waist-to-height ratio (WHtR), waist circumference (WC), body mass index (BMI) and height) with all-cause mortality in 7447 participants at high cardiovascular risk from the PREDIMED trial. Forty three percent of them were men (55 to 80 years) and 57% were women (60 to 80 years). All of them were initially free of cardiovascular disease. The recruitment took place in 11 recruiting centers between 2003 and 2009.

Results

After adjusting for age, sex, smoking, diabetes, hypertension, intervention group, family history of coronary heart disease, and leisure-time physical activity, WC and WHtR were found to be directly associated with a higher mortality after 4.8 years median follow-up. The multivariable-adjusted HRs for mortality of WHtR (cut-off points: 0.60, 0.65, 0.70) were 1.02 (0.78–1.34), 1.30 (0.97–1.75) and 1.55 (1.06–2.26). When we used WC (cut-off points: 100, 105 and 110 cm), the multivariable adjusted Hazard Ratios (HRs) for mortality were 1.18 (0.88–1.59), 1.02 (0.74–1.41) and 1.57 (1.19–2.08). In all analyses, BMI exhibited weaker associations with mortality than WC or WHtR. The direct association between WHtR and overall mortality was consistent within each of the three intervention arms of the trial.

Conclusions

Our study adds further support to a stronger association of abdominal obesity than BMI with total mortality among elderly subjects at high risk of cardiovascular disease. We did not find evidence to support that the PREDIMED intervention was able to counterbalance the harmful effects of increased adiposity on total mortality.

Trial Registration

Controlled-Trials.com ISRCTN35739639     

Relationships between serotonergic and cannabinoid system in depressive‐like behavior: a PET study with [11C]‐DASB

Chronic stress represents a major environmental risk factor for mood disorders in vulnerable individuals. The neurobiological mechanisms underlying these disorders involve serotonergic and endocannabinoid systems. In this study, we have investigated the relationships between these two neurochemical systems in emotional control using genetic and imaging tools. CB₁ cannabinoid receptor knockout mice (KO) and wild‐type littermates (WT) were exposed to chronic restraint stress. Depressive‐like symptoms (anhedonia and helplessness) were produced by chronic stress exposure in WT mice. CB₁ KO mice already showed these depressive‐like manifestations in non‐stress conditions and the same phenotype was observed after chronic restraint stress. Chronic stress similarly impaired long‐term memory in both genotypes. In addition, brain levels of serotonin transporter (5‐HTT) were assessed using positron emission tomography. Decreased brain 5‐HTT levels were revealed in CB₁ KO mice under basal conditions, as well as in WT mice after chronic stress. Our results show that chronic restraint stress induced depressive‐like behavioral alterations and brain changes in 5‐HTT levels similarly to those revealed in CB₁ KO mice in non‐stressed conditions. These results underline the relevance of chronic environmental stress on serotonergic and endocannabinoid transmission for the development of depressive symptoms.

     

Langerhans cell sarcoma: Response to radiotherapy

We present the case of a patient with progressive Langerhans cell sarcoma whose cutaneous lesions and nodal masses were treated with palliative radiotherapy. Response to relatively low doses of radiotherapy was both good and sustained. We recommend a dose of 15–30 Gy depending on treatment intention and volume of the lesions.     

Genetic relationships between parishes in the Ebro delta region (Spain) as estimated by migration matrix and surnames

To determine whether there are preferential relationships among individuals from the different parishes of the Ebro River delta region, we analyzed the population relationships, taking into account both the birthplaces of the spouses and their surname frequencies. We used data from the 9,085 marriages recorded in the Ebro delta area between 1939 and 1995. Using each spouse's birthplace, we calculated the distances between the subject populations by means of the squared Euclidean distance. Also, from the surname frequencies in the marriages we obtained certain kinship measurements. In both analyses the results show a clear differentiation between the parish of Amposta and the rest of the parishes. This difference is mainly due to a greater number of marriages in which delta outsiders participated and can be related to the greater surname diversity and lesser endogamy observed in this population. On the other hand, if only endogamous marriages are taken into account, there is clearly a differentiation between the parishes from both banks of the river, with a strong homogeneity among the northside parishes. We compared the distances obtained from the birthplaces, the kinship parameters obtained from the surnames, and two geographic distance matrixes by means of a Mantel test, and the results show a strong and significant correlation between them when all marriages are considered. If, on the other hand, only endogamous marriages are taken into account, the barrier effect of the river on the interparish relationships can be appreciated.     

Solution structure and folding characteristics of the C-terminal SH3 domain of c-Crk-II

Crk-II is a signaling adaptor protein that is involved in many cellular processes including apoptosis, proliferation, and differentiation. It has a modular domain architecture consisting of an Src homology 2 domain (SH2) followed by two Src homology 3 (SH3) domains. The structures and ligand-binding properties of the SH2 and the middle SH3 domains are well-characterized. Several studies suggest that the C-terminal SH3 domain plays an important regulatory role in the protein; however, no structural information is available on this domain, and relatively little is known about its binding partners. In the current work, we have solved the solution NMR structure of the C-terminal SH3 domain. The domain adopts the standard SH3 fold comprising a five-stranded beta barrel. In agreement with alignment and modeling studies, the structure indicates that the canonical-binding surface of the SH3 domain is unusually polar and suggests that this domain may not bind typical PXXP ligands or that it may bind them with reduced affinity. Thermodynamic and kinetic studies show that the domain folds in a reversible two-state manner and that the stability of the fold is similar to that observed for other SH3 domains. These studies offer some insight into the likely structural and thermodynamic consequences of point mutations in the cSH3 domain that are known to deregulate Crk-II function. Our results set the stage for a better understanding the role of the cSH3 domain in the context of the full-length protein.     

Bioaerosol emission from wastewater treatment plants

In this report we describe the results of astudy conducted to better estimate airbornemicroorganisms present in wastewater treatmentplants (WWTP) environments. Air samples weretaken with the Air Sampler MAS 100 impactor(Merck) at each stage of an activated-sludgeWWTP (pre-treatment, primary clarifiers,aeration basins and sludge processors), inorder to determine levels of contaminationaccording to work stations. Culture methodswere used to investigate heterotrophic platecount, moulds and yeasts, total and fecalcoliforms, Pseudomonas aeruginosa andspecies belonging to Mycobacteriumtuberculosis complex, whereas these lastmicroorganisms were also analysed by PolymeraseChain Reaction (PCR) methods. Statisticalanalysis showed that pretreatment and primaryclarifiers were the stages with the highestemission of bioaerosols, and that bioaerosolconcentration at each stage depended on windspeed and daily inflow at the WWTP. Lowconcentrations of P. aeruginosa werefound isolated at pretreatment and primaryclarifiers; however, species of M.tuberculosis complex were not detected at anystage of the treatment plant.     

Effects of UV-B irradiated algae on zooplankton grazing

We tested the effects of UV-B stressed algae on grazing rates of zooplankton. Four algal species (Chlamydomonas reinhardtii, Cryptomonas sp., Scenedesmus obliquus and Microcystis aeruginosa) were used as food and fed to three zooplankton species (Daphnia galeata, Bosmina longirostris and Brachionus calyciflorus), representing different taxonomic groups. The phytoplankton species were cultured under PAR conditions, and under PAR supplemented with UV-B radiation at two intensities (0.3 W m^–2 and 0.7 W m^–2, 6 hours per day). Ingestion and incorporation experiments were performed at two food levels (0.1 and 1.0 mg C l^–1) using radiotracer techniques. The effect of food concentration on ingestion and incorporation rate was significant for all three zooplankton species, but the effect of UV-B radiation was more complex. The reactions of the zooplankton species to UV-B stressed algae were different. UV-B stressed algae did not affect Daphnia grazing rates. For Bosmina the rates increased when feeding on UV-B stressed Microcystis and decreased when feeding on UV-B stressed Chlamydomonas, compared with non-stressed algae. Brachionus grazing rates were increased when feeding on UV-B stressed Cryptomonas and UV-B stressed Scenedesmus, and decreased when feeding on UV-B stressed Microcystis, compared with non-stressed algae. These results suggest that on a short time scale UV-B radiation may result in increased grazing rates of zooplankton, but also in decreased grazing rates. Long term effects of UV-B radiation on phytoplankton and zooplankton communities are therefore difficult to predict.     

Detailed architecture of a DNA translocating machine: the high-resolution structure of the bacteriophage phi29 connector particle.

The three-dimensional crystal structure of the bacteriophage phi29 connector has been solved and refined to 2.1A resolution. This 422 kDa oligomeric protein connects the head of the phage to its tail and translocates the DNA into the prohead during packaging. Each monomer has an elongated shape and is composed of a central, mainly alpha-helical domain that includes a three-helix bundle, a distal alpha/beta domain and a proximal six-stranded SH3-like domain. The protomers assemble into a 12-mer, propeller-like, super-structure with a 35 A wide central channel. The surface of the channel is mainly electronegative, but it includes two lysine rings 20 A apart. On the external surface of the particle a hydrophobic belt extends to the concave area below the SH3-like domain, which forms a crown that retains the particle in the head. The lipophilic belt contacts the non-matching symmetry vertex of the capsid and forms a bearing for the connector rotation. The structure suggests a translocation mechanism in which the longitudinal displacement of the DNA along its axis is coupled to connector spinning.