The Antioxidant Potential of the Mediterranean Diet in Patients at High Cardiovascular Risk: An In-Depth Review of the PREDIMED

Cardiovascular disease (CVD) is the leading global cause of death. Diet is known to be important in the prevention of CVD. The PREDIMED trial tested a relatively low-fat diet versus a high-fat Mediterranean diet (MedDiet) for the primary prevention of CVD. The resulting reduction of the CV composite outcome resulted in a paradigm shift in CV nutrition. Though many dietary factors likely contributed to this effect, this review focuses on the influence of the MedDiet on endogenous antioxidant systems and the effect of dietary polyphenols. Subgroup analysis of the PREDIMED trial revealed increased endogenous antioxidant and decreased pro-oxidant activity in the MedDiet groups. Moreover, higher polyphenol intake was associated with lower incidence of the primary outcome, overall mortality, blood pressure, inflammatory biomarkers, onset of new-onset type 2 diabetes mellitus (T2DM), and obesity. This suggests that polyphenols likely contributed to the lower incidence of the primary event in the MedDiet groups. In this article, we summarize the potential benefits of polyphenols found in the MedDiet, specifically the PREDIMED cohort. We also discuss the need for further research to confirm and expand the findings of the PREDIMED in a non-Mediterranean population and to determine the exact mechanisms of action of polyphenols

Influence of patient symptoms and physical findings on general practitioners' treatment of respiratory tract infections: a direct observation study

BACKGROUND: The high rate of antibiotic prescriptions general practitioners (GPs) make for respiratory tract infections (RTI) are often explained by non-medical reasons e.g. an effort to meet patient expectations. Additionally, it is known that GPs to some extent believe in the necessity of antibiotic treatment in patients with assumed bacterial infections and therefore attempt to distinguish between viral and bacterial infections by history taking and physical examination. The influence of patient complaints and physical examination findings on GPs' prescribing behaviour was mostly investigated by indirect methods such as questionnaires. METHODS: Direct, structured observation during a winter "cough an cold period" in 30 (single handed) general practices. All 273 patients with symptoms of RTI (age above 14, median 37 years, 51% female) were included. RESULTS: The most frequent diagnoses were 'uncomplicated upper RTI/common cold' (43%) followed by 'bronchitis' (26%). On average, 1.8 (95%-confidence interval (CI): 1.7–2.0) medicines per patient were prescribed (cough-and-cold preparations in 88% of the patients, antibiotics in 49%). Medical predictors of antibiotic prescribing were pathological findings in physical examination such as coated tonsils (odds ratio (OR) 15.4, 95%-CI: 3.6–66.2) and unspecific symptoms like fatigue (OR 3.1, 95%-CI 1.4–6.7), fever (OR 2.2, 95%-CI: 1.1–4.5) and yellow sputum (OR 2.1, 95%-CI: 1.1–4.1). Analysed predictors explained 70% of the variance of antibiotic prescribing (R(2 )= 0,696). Efforts to reduce antibiotic prescribing, e.g. recommendations for self-medication, counselling on home remedies or delayed antibiotic prescribing were rare. CONCLUSIONS: Patient complaints and pathological results in physical examination were strong predictors of antibiotic prescribing. Efforts to reduce antibiotic prescribing should account for GPs' beliefs in those (non evidence based) predictors. The method of direct observation was shown to be accepted both by patients and GPs and offered detailed insights into the GP-patient-interaction

Identification and characterization of a novel non-structural protein of bluetongue virus

Bluetongue virus (BTV) is the causative agent of a major disease of livestock (bluetongue). For over two decades, it has been widely accepted that the 10 segments of the dsRNA genome of BTV encode for 7 structural and 3 non-structural proteins. The non-structural proteins (NS1, NS2, NS3/NS3a) play different key roles during the viral replication cycle. In this study we show that BTV expresses a fourth non-structural protein (that we designated NS4) encoded by an open reading frame in segment 9 overlapping the open reading frame encoding VP6. NS4 is 77–79 amino acid residues in length and highly conserved among several BTV serotypes/strains. NS4 was expressed early post-infection and localized in the nucleoli of BTV infected cells. By reverse genetics, we showed that NS4 is dispensable for BTV replication in vitro, both in mammalian and insect cells, and does not affect viral virulence in murine models of bluetongue infection. Interestingly, NS4 conferred a replication advantage to BTV-8, but not to BTV-1, in cells in an interferon (IFN)-induced antiviral state. However, the BTV-1 NS4 conferred a replication advantage both to a BTV-8 reassortant containing the entire segment 9 of BTV-1 and to a BTV-8 mutant with the NS4 identical to the homologous BTV-1 protein. Collectively, this study suggests that NS4 plays an important role in virus-host interaction and is one of the mechanisms played, at least by BTV-8, to counteract the antiviral response of the host. In addition, the distinct nucleolar localization of NS4, being expressed by a virus that replicates exclusively in the cytoplasm, offers new avenues to investigate the multiple roles played by the nucleolus in the biology of the cell

Frequency of nut consumption and mortality risk in the PREDIMED nutrition intervention trial

BackgroundProspective studies in non-Mediterranean populations have consistently related increasing nut consumption to lower coronary heart disease mortality. A small protective effect on all-cause and cancer mortality has also been suggested. To examine the association between frequency of nut consumption and mortality in individuals at high cardiovascular risk from Spain, a Mediterranean country with a relatively high average nut intake per person.MethodsWe evaluated 7,216 men and women aged 55 to 80 years randomized to 1 of 3 interventions (Mediterranean diets supplemented with nuts or olive oil and control diet) in the PREDIMED (‘PREvención con DIeta MEDiterránea’) study. Nut consumption was assessed at baseline and mortality was ascertained by medical records and linkage to the National Death Index. Multivariable-adjusted Cox regression and multivariable analyses with generalized estimating equation models were used to assess the association between yearly repeated measurements of nut consumption and mortality.ResultsDuring a median follow-up of 4.8 years, 323 total deaths, 81 cardiovascular deaths and 130 cancer deaths occurred. Nut consumption was associated with a significantly reduced risk of all-cause mortality (P for trend 3 servings/week (32% of the cohort) had a 39% lower mortality risk (hazard ratio (HR) 0.61; 95% CI 0.45 to 0.83). A similar protective effect against cardiovascular and cancer mortality was observed. Participants allocated to the Mediterranean diet with nuts group who consumed nuts >3 servings/week at baseline had the lowest total mortality risk (HR 0.37; 95% CI 0.22 to 0.66).ConclusionsIncreased frequency of nut consumption was associated with a significantly reduced risk of mortality in a Mediterranean population at high cardiovascular risk.Please see related commentary: http://www.biomedcentral.com/1741-7015/11/165.Trial registrationClinicaltrials.gov. International Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005

Effect of within-species plant genotype mixing on habitat preference of a polyphagous insect predator

The effects of within-species plant genotype mixing on the habitat preference of a polyphagous ladybird were studied. Plant species diversity is often claimed to positively affect habitat preferences of insect predators, but the effects of within-species genotype diversity have not been extensively studied. In a field experiment with different barley (Hordeum vulgare) genotypes in mixed and pure stands, adult seven-spot ladybird Coccinella septempunctata, a polyphagous predator, preferred a specific combination of genotypes over the single genotypes alone before aphids had arrived in the crop, and again when aphids were emigrating. In laboratory experiments on adult ladybird orientation to odour from barley, ladybirds were attracted/arrested by the mixed odour of the same barley genotype mixture that was preferred in the field. Exposure of one barley genotype to volatiles from the other also caused the odour of the exposed plants to become more attractive to ladybirds. The results support the hypothesis that plant volatiles may attract or arrest foraging adult ladybirds, contributing to the selection of favourable habitats, and they show that within-species plant genotype mixing can shape interactions within multitrophic communities

Wnt5a Regulates Ventral Midbrain Morphogenesis and the Development of A9–A10 Dopaminergic Cells In Vivo

Wnt5a is a morphogen that activates the Wnt/planar cell polarity (PCP) pathway and serves multiple functions during development. PCP signaling controls the orientation of cells within an epithelial plane as well as convergent extension (CE) movements. Wnt5a was previously reported to promote differentiation of A9–10 dopaminergic (DA) precursors in vitro. However, the signaling mechanism in DA cells and the function of Wnt5a during midbrain development in vivo remains unclear. We hereby report that Wnt5a activated the GTPase Rac1 in DA cells and that Rac1 inhibitors blocked the Wnt5a-induced DA neuron differentiation of ventral midbrain (VM) precursor cultures, linking Wnt5a-induced differentiation with a known effector of Wnt/PCP signaling. In vivo, Wnt5a was expressed throughout the VM at embryonic day (E)9.5, and was restricted to the VM floor and basal plate by E11.5–E13.5. Analysis of Wnt5a−/− mice revealed a transient increase in progenitor proliferation at E11.5, and a precociously induced NR4A2+ (Nurr1) precursor pool at E12.5. The excess NR4A2+ precursors remained undifferentiated until E14.5, when a transient 25% increase in DA neurons was detected. Wnt5a−/− mice also displayed a defect in (mid)brain morphogenesis, including an impairment in midbrain elongation and a rounded ventricular cavity. Interestingly, these alterations affected mostly cells in the DA lineage. The ventral Sonic hedgehog-expressing domain was broadened and flattened, a typical CE phenotype, and the domains occupied by Ngn2+ DA progenitors, NR4A2+ DA precursors and TH+ DA neurons were rostrocaudally reduced and laterally expanded. In summary, we hereby describe a Wnt5a regulation of Wnt/PCP signaling in the DA lineage and provide evidence for multiple functions of Wnt5a in the VM in vivo, including the regulation of VM morphogenesis, DA progenitor cell division, and differentiation of NR4A2+ DA precursors

The Role of bZIP Transcription Factors in Green Plant Evolution: Adaptive Features Emerging from Four Founder Genes

BACKGROUND: Transcription factors of the basic leucine zipper (bZIP) family control important processes in all eukaryotes. In plants, bZIPs are regulators of many central developmental and physiological processes including photomorphogenesis, leaf and seed formation, energy homeostasis, and abiotic and biotic stress responses. Here we performed a comprehensive phylogenetic analysis of bZIP genes from algae, mosses, ferns, gymnosperms and angiosperms. METHODOLOGY/PRINCIPAL FINDINGS: We identified 13 groups of bZIP homologues in angiosperms, three more than known before, that represent 34 Possible Groups of Orthologues (PoGOs). The 34 PoGOs may correspond to the complete set of ancestral angiosperm bZIP genes that participated in the diversification of flowering plants. Homologous genes dedicated to seed-related processes and ABA-mediated stress responses originated in the common ancestor of seed plants, and three groups of homologues emerged in the angiosperm lineage, of which one group plays a role in optimizing the use of energy. CONCLUSIONS/SIGNIFICANCE: Our data suggest that the ancestor of green plants possessed four bZIP genes functionally involved in oxidative stress and unfolded protein responses that are bZIP-mediated processes in all eukaryotes, but also in light-dependent regulations. The four founder genes amplified and diverged significantly, generating traits that benefited the colonization of new environments