Background Patients recovering from aneurysmal subarachnoid hemorrhage (SAH) are at risk for developing delayed cerebral ischemia (DCI). Experimental and human studies implicate the vasoconstrictor P450 eicosanoid 20-hydroxyeicosatetraenoic acid (20-HETE) in the pathogenesis of DCI. To date, no studies have evaluated the role of vasodilator epoxyeicosatrienoic acids (EETs) in DCI. Methods Using mass spectrometry, we measured P450 eicosanoids in cerebrospinal fluid (CSF) from 34 SAH patients from 1 to 14 days after admission. CSF eicosanoid levels were compared in patients who experienced DCI versus those who did not. We then studied the effect of EETs in a model of SAH using mice lacking the enzyme soluble epoxide hydrolase, which catabolizes EETs into their inactive diol. To assess changes in vessel morphology and cortical perfusion in the mouse brain we used optical microangiography, a non-invasive coherence based imaging technique. Results Along with increases in 20-HETE, we found that CSF levels of 14, 15-EET were elevated in SAH patients compared to control CSF, and levels were significantly higher in patients who experienced DCI compared to those who did not. Mice lacking sEH had elevated 14, 15-EET and were protected from the delayed decrease in microvascular cortical perfusion after SAH, compared to wild type mice. Conclusions Our findings suggest that P450 eicosanoids play an important role in the pathogenesis of DCI. While 20-HETE may contribute to the development of DCI, 14, 15-EET may afford protection against DCI. Strategies to enhance 14, 15-EET, including sEH inhibition, should be considered as part of a comprehensive approach to preventing DCI.

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Object Patients with aneurysmal subarachnoid hemorrhage (SAH) are at high risk for delayed cerebral ischemia (DCI) and stroke. Epoxyeicosatrienoic acids (EETs) play an important role in cerebral blood flow regulation and neuroprotection after brain injury. Polymorphisms in the gene for the enzyme soluble epoxide hydrolase (sEH), which inactivates EETs, are associated with ischemic stroke risk and neuronal survival after ischemia. In this prospective observational study of patients with SAH we compare vital and neurologic outcomes based on functional polymorphisms of sEH. Methods Allelic discrimination based on quantitative real-time PCR was used to differentiate wild type (WT) sEH from K55R heterozygotes (predictive of increased sEH activity and reduced EETs) and R287Q heterozygotes (predictive of decreased sEH activity and increased EETs). The primary outcome was new stroke after SAH. Secondary outcomes were mortality, Glasgow outcome scale (GOS) score and neurologic deterioration attributable to delayed cerebral ischemia (DCI). Results Multivariable logistic regression models adjusted for admission age and Glasgow coma scale revealed an increase in the odds of new stroke (OR 5.48 (1.51–19.91) and mortality (OR 7.62 (1.19–48.7) in the K55R group, but no change in the odds of new stroke 0.56 (0.16–1.96) or death 3.09 (0.51–18.52) in patients with R287Q genotype, compared to wild-type sEH. R287Q genotype was associated with reduced odds of having a GOS ≤ 3 (0.23 (0.06–0.82)). There were no significant differences in the odds of neurologic deterioration due to DCI. Conclusions Genetic polymorphisms of sEH are associated with neurologic and vital outcomes after aneurysmal subarachnoid hemorrhage.

Abstract:Recently, much of the literature on sharing in cities has focused on the sharing economy, in which people use online platforms to share underutilized assets in the marketplace. This view of sharing is too narrow for cities, as it neglects the myriad of ways, reasons, and scales in which citizens share in urban environments. Research presented here by the Liveable Cities team in the form of participant workshops in Lancaster and Birmingham, UK, suggests that a broader approach to Sustainability 2017, 9, 701; doi:10.3390/su9050701 www.mdpi.com/journal/sustainability Sustainability 2017, 9, 701 2 of 16 understanding sharing in cities is essential. The research also highlighted tools and methods that may be used to help to identify sharing in communities. The paper ends with advice to city stakeholders, such as policymakers, urban planners, and urban designers, who are considering how to enhance sustainability in cities through sharing.

:  Recent epidemiological studies have reported an increased risk of leukemia in adults and children near overhead high voltage powerlines at distances beyond the measured range of the direct electric and magnetic fields. Corona ions are emitted by powerlines, forming a plume that is carried away from the line by the wind. The plume generates highly variable disturbances in the atmospheric electric field of tens to a few hundred V/m on time scales from seconds to minutes. Such disturbances can be seen up to several hundred meters from powerlines. It is hypothesized that these random disturbances result in the disruption of nocturnal melatonin synthesis and related circadian rhythms, in turn leading to increased risk of a number of adverse health effects including leukemia. In support of the hypothesis, it is noted that melatonin is highly protective of oxidative damage to the human hemopoietic system. A review of electric field studies provides evidence that (i) diurnal variation in the natural atmospheric electric field may itself act as a weak Zeitgeber; (ii) melatonin disruption by electric fields occurs in rats; (iii) in humans, disturbances in circadian rhythms have been observed with artificial fields as low at 2.5 V/m. Specific suggestions are made to test the aspects of the hypothesis.