IntroductionHealth research is one mechanism to improve population-level health and should generally match the health needs of populations. However, there have been limited data to assess the trends in national-level cardiovascular research output, even as cardiovascular disease [CVD] has become the leading cause of morbidity and mortality worldwide.Materials and MethodsWe performed a time trends analysis of cardiovascular research publications (1999–2008) downloaded from Web of Knowledge using a iteratively-tested cardiovascular bibliometric filter with >90% precision and recall. We evaluated cardiovascular research publications, five-year running actual citation indices [ACIs], and degree of international collaboration measured through the ratio of the fractional count of addresses from one country against all addresses for each publication.Results and DiscussionGlobal cardiovascular publication volume increased from 40 661 publications in 1999 to 55 284 publications in 2008, which represents a 36% increase. The proportion of cardiovascular publications from high-income, Organization for Economic Cooperation and Development [OECD] countries declined from 93% to 84% of the total share over the study period. High-income, OECD countries generally had higher fractional counts, which suggest less international collaboration, than lower income countries from 1999–2008. There was an inverse relationship between cardiovascular publications and age-standardized CVD morbidity and mortality rates, but a direct, curvilinear relationship between cardiovascular publications and Human Development Index from 1999–2008.ConclusionsCardiovascular health research output has increased substantially in the past decade, with a greater share of citations being published from low- and middle-income countries. However, low- and middle-income countries with the higher burdens of cardiovascular disease continue to have lower research output than high-income countries, and thus require targeted research investments to improve cardiovascular health.
Endothelin converting Enzyme-1 (ECE-1) is essential for the production of Endothelin-1 (ET-1), which is associated with vasospasm following subarachnoid hemorrhage (SAH). We have previously demonstrated the presence of a catalytically active soluble form of ECE-1 in the media of endothelial cells. We aimed to determine if this form of ECE-1 exists in vivo, in cerebrospinal fluid (CSF) of SAH patients. We examined CSF taken from SAH subjects for the presence of soluble ECE-1 using a bradykinin based quenched fluorescent substrate assay. We obtained further confirmation by characterizing the CSF mediated cleavage products of BigET-1 and BigET 18 -34 (6 g/ml) using mass spectrometry. The specificity of cleavage was confirmed using the ECE-1 inhibitor CGS35066 5nmol/L. SAH CSF samples had mean ECE-1 activity of 0.127 ؎ 0.037 mols of substrate cleaved/ l of CSF/24 h. The C-terminal peptides generated upon the cleavage of BigET-1 and BigET 18 -34 were detected 48 h after incubation of these substrates with CSF. Cleavage of these substrates was inhibited by CGS35066. Results of Western blots also produced strong evidence for the presence of truncated soluble ECE-1 in CSF. These results strongly suggest the presence of a truncated but catalytically active form of ECE-1 in the CSF of SAH subjects. Further studies are necessary to determine the biological significance of soluble ECE-1 in CSF of SAH subjects, including an association with vasospasm after SAH. Endothelin-1 (ET-1) 1 is the most potent vasoconstrictor in the central nervous system. Elevated levels of ET-1 in cerebrospinal fluid (CSF) have been implicated in the pathogenesis of cerebral vasospasm following subarachnoid hemorrhage (SAH) (1). However, it is not known whether the production of ET-1 within the CSF space contributes to the pathogenesis of vasospasm. ET-1 is produced upon the cleavage of its precursor BigET-1 by the highly specific metalloprotease Endothelin Converting Enzyme-1 (ECE-1). The rate-limiting step of ET-1 production is the expression and localization of ECE-1, whose catalytic activity is confined to the extracellular C-terminal domain. Previously, we have demonstrated that the catalytically active C terminus can be shed from the cell surface (2). This results in the release of a truncated but catalytically active form of ECE-1 into the extracellular milieu.Although the presence of a soluble form of ECE-1 has been demonstrated in vitro, it is yet to be shown in any human biological fluid. In this study, we have used a combination of mass spectrometry, Western blotting as well as quenched fluorescent substrate (QFS) based enzyme assays to demonstrate for the first time the presence of catalytically active, soluble form of ECE-1 in CSF of SAH subjects. EXPERIMENTAL PROCEDURESCSF Sample Collection-CSF samples were obtained from a prospective biorepository of SAH and non-SAH hydrocephalus human subjects in accordance with local institutional review board approved protocol. Detailed descriptions of biorepository methods have been previously pu...
In a study of 592 children without Horner syndrome, the average pupillary size increased with age, but the degree of anisocoria remained stable with increasing age. Over half of the children studied had anisocoria up to 0.5 mm (62.84%), but rarely had anisocoria greater than 1.3 mm (3.70%). In children with a diagnosis of Horner syndrome, the majority had anisocoria greater than 1.3 mm, with the discrepancy in pupil size becoming more apparent in low levels of light intensity. Anisocoria greater than 1.3 mm is unlikely to be physiologic in a child; therefore, he or she should be carefully evaluated for other localizing signs, such as ptosis, anhidrosis, and neck mass. [J Pediatr Ophthalmol Strabismus. 2016;53(3):186-189.].
Introduction: Growing evidence suggest inflammation plays a key role in the pathogenesis of vasospasm (VSP) and secondary ischemic injury following subarachnoid hemorrhage (SAH). While elevations of select pro-inflammatory cytokines such interleukin (IL) 6 in cerebrospinal fluid (CSF) are linked to VSP in SAH, it is unclear which cytokines are measurable in SAH CSF. We explore a panel of cytokines and chemokines during peak VSP time window in human SAH in search for novel CSF biomarkers. Methods: CSF samples were collected through external ventricular drain from a prospective SAH cohort. Clinical outcome was evaluated at 3- and 6-months using modified Rankin scores (mRS). Poor outcome was defined as mRS>2. Angiographic VSP was defined as >50% reduction in caliber of any vessel on post-SAH day 7 cerebral angiogram. In 29 SAH subjects, we compared post-SAH day 5 CSF biomarker profile with respect to outcome and VSP using Milliplex panel (EMD Millipore) with 42 biomarkers. Continuous variables were compared using Wilcoxon rank sum test. Benjamin-Hochberg correction was used for multiple comparisons. Results: VSP occurred in 45% of the SAH cohort, and 52% of this cohort had good outcome at 3 month. Of the 42 biomarkers, 39 were measurable in SAH CSF. Elevated CSF IL-4 showed strongest trend towards association with good outcome at 3-month (p=0.0049) and at 6-months (p=0.02). Other CSF biomarkers showing trend toward association with outcome include epidermal growth factor (p=0.035), fractalkine (p=0.045), and platelet-derived growth factor AA (p=0.024). Elevation of a different cluster of biomarkers showed trend towards association with VSP: IL-5 (p=0.041), IL-17A (p=0.049), and IL-2 (p=0.047). No single marker reached significance at p<0.05 level after adjustment for multiple comparisons. Conclusions: Differential expression of cytokine and chemokines are present in CSF post SAH. Results from this small pilot study suggest a possible association between elevation of CSF anti-inflammatory cytokine IL-4 and good SAH outcome. This is consistent with animal studies showing IL-4 attenuates ischemic injury and promotes neuroprotection. Larger targeted studies are necessary to investigate the role of cytokines and specifically CSF IL-4 in SAH outcome.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.