The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701).

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Two observations highlight the importance of this review. The first observation is that high blood pressure is the most frequent comorbid condition in cancer registries which directly affects the prognosis of the patient. The second observation is that long-term cancer survivors now have a higher risk of cardiovascular disease than of recurrent cancer, and hypertension contributes to this risk. New approaches to cancer chemotherapy disrupt angiogenesis; subjects receiving these agents often have an associated increase in blood pressure. In this article we concentrate on observations published over the past 2 years in this rapidly developing field, outline putative mechanisms and time frames for these prohypertensive effects, and conclude with some management recommendations based on current knowledge.

Essential oil components from turmeric (Curcuma longa L.) are documented for neuroprotective, anti-cancer, anti-thrombotic and antioxidant effects. The present study aimed to investigate the disease-modifying potential of curcuma oil (C. oil), a lipophilic component from C. longa L., in hyperlipidaemic hamsters. Male golden Syrian hamsters were fed a chow or high-cholesterol (HC) and fat-rich diet with or without C. oil (30, 100 and 300 mg/kg) for 28 d. In HC diet-fed hamsters, C. oil significantly reduced plasma total cholesterol, LDL-cholesterol and TAG, and increased HDL-cholesterol when compared with the HC group. Similar group comparisons showed that C. oil treatment reduced hepatic cholesterol and oxidative stress, and improved liver function. Hyperlipidaemia-induced platelet activation, vascular dysfunction and repressed eNOS mRNA expression were restored by the C. oil treatment. Furthermore, aortic cholesterol accumulation and CD68 expression were also reduced in the C. oil-treated group. The effect of C. oil at 300 mg/kg was comparable with the standard drug ezetimibe. Delving into the probable anti-hyperlipidaemic mechanism at the transcript level, the C. oil-treated groups fed the chow and HC diets were compared with the chow diet-fed group. The C. oil treatment significantly increased the hepatic expression of PPARa, LXRa, CYP7A1, ABCA1, ABCG5, ABCG8 and LPL accompanied by reduced SREBP-2 and HMGCR expression. C. oil also enhanced ABCA1, ABCG5 and ABCG8 expression and suppressed NPC1L1 expression in the jejunum. In the present study, C. oil demonstrated an anti-hyperlipidaemic effect and reduced lipid-induced oxidative stress, platelet activation and vascular dysfunction. The anti-hyperlipidaemic effect exhibited by C. oil seems to be mediated by the modulation of PPARa, LXRa and associated genes involved in lipid metabolism and transport.

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There is a critical need for cerebroprotective interventions to improve the suboptimal outcomes of patients with ischemic stroke treated with reperfusion strategies. We found that nuclear pyruvate kinase muscle 2 (PKM2), a modulator of systemic inflammation, was upregulated in neutrophils after the onset of ischemic stroke both in humans and in mice. Therefore, we determined the role of PKM2 in stroke pathogenesis utilizing murine models with preexisting comorbidities. We generated novel myeloid cell-specific PKM2-/- mice on wild-type (PKM2fl/flLysMCre+) and hyperlipidemic background (PKM2fl/flLysMCre+Apoe-/-). Controls were littermate PKM2fl/flLysMCre- or PKM2fl/flLysMCre-Apoe-/- mice. Genetic deletion of PKM2 in myeloid cells limited inflammatory response in peripheral neutrophils and reduced neutrophil extracellular traps following cerebral ischemia/reperfusion, suggesting PKM2 promotes neutrophil hyperactivation in the setting of stroke. In the filament and autologous clot/rtPA stroke models, irrespective of sex, deletion of PKM2 in myeloid cells either in wild-type or hyperlipidemic mice reduced infarcts and enhanced long-term sensorimotor recovery. Laser speckle imaging revealed improved regional cerebral blood flow in myeloid cell-specific PKM2-deficient mice that was concomitant with reduced post-ischemic cerebral thrombo-inflammation (intracerebral fibrin(ogen), platelet (CD41-positive) deposition, neutrophil infiltration, and inflammatory cytokines). Mechanistically, PKM2 regulates post-ischemic inflammation in peripheral neutrophils by promoting STAT3 phosphorylation. To enhance the translational significance, we inhibited PKM2 nuclear translocation using a small molecule and found significantly reduced neutrophil hyperactivation and improved short-term and long-term functional outcomes following stroke. Collectively, these findings identify PKM2 as a novel therapeutic target to improve brain salvage and recovery following reperfusion.

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To investigate the consequences of hybridization between species, we studied three replicate hybrid populations that formed naturally between two swordtail fish species, estimating their fine-scale genetic map and inferring ancestry along the genomes of 690 individuals. In all three populations, ancestry from the "minor" parental species is more common in regions of high recombination and where there is linkage to fewer putative targets of selection. The same patterns are apparent in a reanalysis of human and archaic admixture. These results support models in which ancestry from the minor parental species is more likely to persist when rapidly uncoupled from alleles that are deleterious in hybrids. Our analyses further indicate that selection on swordtail hybrids stems predominantly from deleterious combinations of epistatically interacting alleles. U nderstanding speciation is central to understanding evolution, but so much about the process still puzzles us. Foundational work in evolutionary biology envisioned speciation as an ordered process in which reproductive barriers, once established, prevent gene flow between species (1). We now realize, however, that speciation is much more dynamic, with evidence of historical and ongoing hybridization visible in the genomes of myriad species (2-5). The ubiquity of hybridization raises the question of how species that interbreed remain distinct.At least part of the answer lies in widespread selection on hybrid genomes (1). Analyses of hominin and swordtail fish hybrids indicate that ancestry from the "minor" parent species (the parent that contributed less to the gene pool of hybrids) is decreased near functionally important elements (4, 6, 7), presumably because such regions are enriched for harmful alleles. Aside from these observations, however, little is known about how hybrid genomes evolve. Decades of experimental work have demonstrated that Bateson-Dobzhansky-Muller incompatibilities (BDMIs) are a central mechanism underlying reproductive isolation once species are formed (8-10), but the importance of BDMIs in the evolution of hybrid genomes remains unknown, as does the role of other modes of selection. When there is introgression from a species with a smaller effective population size, hybrids may suffer from increased genetic load ("hybridization load") due to the introduction of weakly deleterious alleles (6,11,12). Depending on the environment in which hybrids find themselves, alleles that underlie ecological adaptations in the parental species may also be deleterious (13,14). Complicating matters further, the sources of selection on hybrids will likely vary from system to system, depending on the extent of genetic and ecological differentiation between the parental species as well as the differences in their effective population sizes.Regardless of the source of selection, however, one feature is expected to play a central role in mediating its effects: variation in recombination rates along the genome (6,11,(15)(16)(17). In models of BDMIs, neutral ancest...