Flow diversion with the Pipeline Embolization Device is increasingly used for endovascular treatment of intracranial aneurysms due to high reported obliteration rates and low associated morbidity. ...While obliteration of covered branches in the anterior circulation is generally asymptomatic, this has not been studied within the posterior circulation. The aim of this study was to evaluate the association between branch coverage and occlusion, as well as associated ischemic events in a cohort of patients with posterior circulation aneurysms treated with the Pipeline Embolization Device.
A retrospective review of prospectively maintained databases at 8 academic institutions from 2009 to 2016 was performed to identify patients with posterior circulation aneurysms treated with the Pipeline Embolization Device. Branch coverage following placement was evaluated, including the posterior inferior cerebellar artery, anterior inferior cerebellar artery, superior cerebellar artery, and posterior cerebral artery. If the Pipeline Embolization Device crossed the ostia of the contralateral vertebral artery, its long-term patency was assessed as well.
A cohort of 129 consecutive patients underwent treatment of 131 posterior circulation aneurysms with the Pipeline Embolization Device. Adjunctive coiling was used in 40 (31.0%) procedures. One or more branches were covered in 103 (79.8%) procedures. At a median follow-up of 11 months, 11% were occluded, most frequently the vertebral artery (34.8%). Branch obliteration was most common among asymptomatic aneurysms (
< .001). Ischemic complications occurred in 29 (22.5%) procedures. On multivariable analysis, there was no significant difference in ischemic complications in cases in which a branch was covered (
= .24) or occluded (
= .16).
There was a low occlusion incidence in end arteries following branch coverage at last follow-up. The incidence was higher in the posterior cerebral artery and vertebral artery where collateral supply is high. Branch occlusion was not associated with a significant increase in ischemic complications.
Exenatide (exendin-4) is an incretin mimetic currently marketed as an antidiabetic agent for patients with type 2 diabetes. In preclinical models, a reduction in body weight has also been shown in ...low-fat-fed, leptin receptor-deficient rodents.
To more closely model the polygenic and environmental state of human obesity, we characterized the effect of exenatide on food intake and body weight in high-fat-fed, normal (those with an intact leptin signaling system) rodents. As glucagon-like peptide-1 receptor agonism has been found to elicit behaviors associated with visceral illness in rodents, we also examined the effect of peripheral exenatide on kaolin consumption and locomotor activity.
High-fat-fed C57BL/6 mice and Sprague-Dawley rats were treated with exenatide (3, 10 and 30 microg/kg/day) for 4 weeks via subcutaneously implanted osmotic pumps. Food intake and body weight were assessed weekly. At 4 weeks, body composition and plasma metabolic profiles were measured. Kaolin consumption and locomotor activity were measured in fasted Sprague-Dawley rats following a single intraperitoneal injection of exenatide (0.1-10 microg/kg). Exenatide treatment in mice and rats dose-dependently decreased food intake and body weight; significant reductions in body weight gain were observed throughout treatment at 10 and 30 microg/kg/day (P<0.05). Decreased body weight gain was associated with a significant decrease in fat mass (P<0.05) with sparing of lean tissue. Plasma cholesterol, triglycerides and insulin were also significantly reduced (P<0.05). Exenatide at 10 microg/kg significantly reduced food intake (P<0.05) but failed to induce kaolin intake. In general, locomotor activity was reduced at doses of exenatide that decreased food intake, although a slightly higher dose was required to produce significant changes in activity.
Systemic exenatide reduces body weight gain in normal, high-fat-fed rodents, a model that parallels human genetic variation and food consumption patterns, and may play a role in metabolic pathways mediating food intake.
Peptide YY (PYY) is a 36 amino-acid peptide secreted from ileal L cells following meals. The cleaved subpeptide PYY3-36 is biologically active and may constitute the majority of circulating PYY-like ...immunoreactivity. The peptide family that includes PYY, pancreatic peptide and neuropeptide Y is noted for its orexigenic effect following intracerebroventricular administration.
To investigate the effects of peripheral (intraperitoneal and chronic subcutaneous) infusions of PYY3-36 on food intake, body weight and glycemic indices.
Food intake was measured in normal mice and in several rodent models of obesity and type II diabetes. In marked contrast to the reported central orexigenic effects, in the present study, PYY3-36 acutely inhibited food intake by up to 45%, with an ED(50) of 12.5 microg/kg in fasted female NIH/Swiss mice. A 4-week infusion reduced weight gain in female ob/ob mice, without affecting the cumulative food intake. In diet-induced obese male mice, PYY3-36 infusion reduced cumulative food intake, weight gain and epididymal fat weight (as a fraction of carcass) with similar ED(50)'s (466, 297 and 201 microg/kg/day, respectively) and prevented a diet-induced increase in HbA1c. Infusion at 100 microg/kg/day for 8 weeks in male fa/fa rats reduced the weight gain (288+/-11 vs 326+/-12 g in saline-infused controls; P<0.05), similar to effects in a pair-fed group. In female ob/ob and db/db mice, there was no acute effect of PYY3-36 on plasma glucose concentrations. In male diabetic fatty Zucker rats, PYY3-36 infused for 4 weeks reduced HbA1c and fructosamine (ED(50)'s 30 and 44 microg/kg/day).
Peripheral PYY3-36 administration reduced the food intake, body weight gain and glycemic indices in diverse rodent models of metabolic disease of both sexes. These findings justify further exploration of the potential physiologic and therapeutic roles of PYY3-36.
We report findings of strong anomalies in both mutual inductance and inelastic Raman spectroscopy measurements of single-unit-cell FeSe film grown on Nb-doped SrTiO3, which occur near the temperature ...where the superconductinglike energy gap opens. Analysis suggests that the anomaly is associated with a broadened ferroelectric transition in a thin layer near the FeSe/SrTiO3 interface. The coincidence of the ferroelectric transition and gap-opening temperatures adds credence to the central role played by the film-substrate interaction on the strong Cooper pairing in this system. We discuss scenarios that could explain such a coincidence.
A synthetic five-part molecular device has been prepared that uses a multistep electron transfer strategy similar to that of photosynthetic organisms to capture light energy and convert it to ...chemical potential in the form of long-lived charge separation. It consists of two covalently linked porphyrin moieties, one containing a zinc ion (P$_{Zn}$) and the other present as the free base (P). The metallated porphyrin bears a carotenoid polyene (C) and the other a diquinone species (Q$_A$-Q$_B$). Excitation of the free-base porphyrin in a chloroform solution of the pentad yields an initial charge-separated state, C-P$_{Zn}$-P$^{{\cdot}+}$-Q$_A^{{\cdot}-}$-Q$_B$, with a quantum yield of 0.85. Subsequent electron transfer steps lead to a final charge-separated state, C$^{{\cdot}+}$-P$_{Zn}$-P-Q$_A$-Q$_B^{{\cdot}-}$, which is formed with an overall quantum yield of 0.83 and has a lifetime of 55 microseconds. Irradiation of the free-base form of the pentad, C-P-P-Q$_A$-Q$_B$, gives a similar charge-separated state with a lower quantum yield (0.15 in dichloromethane), although the lifetime is increased to ∼340 microseconds. The artificial photosynthetic system preserves a significant fraction (∼1.0 electron volt) of the initial excitation energy (1.9 electron volts) in the long-lived, charge-separated state.
The antifibrotic effects of the peptide hormone relaxin on cardiac and renal fibrosis were studied in 9- to 10-month-old male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats ...(WKY). Rats (n=8 to 9 per group) were allocated into 3 groups: WKY controls, vehicle-treated SHR (SHR-V), and relaxin-treated SHR (SHR-R). Relaxin (0.5 mg/kg per day) was administered via subcutaneously implanted osmotic mini-pumps over 2 weeks before hearts and kidneys were harvested for analysis. Collagen content was analyzed by hydroxyproline assay, gel electrophoresis, and quantitative histology. Zymography was used to determine matrix metalloproteinase (MMP) expression and Western blotting to determine proliferating cell nuclear antigen (PCNA) expression and alpha-smooth muscle actin (alpha-SMA)/myofibroblast expression, whereas cardiac hypertrophy was assessed by myocyte size and real-time polymerase chain reaction of associated genes. The left ventricular (LV) myocardium of SHR-V contained increased collagen levels (by 25+/-1%, P<0.01 using biochemical analysis and 3-fold; P<0.01 using quantitative histology), enhanced expression of PCNA (by 70+/-8%; P<0.01), alpha-SMA (by 32+/-2%; P<0.05), and the collagen-degrading enzyme MMP-9 (by 70+/-6%; P<0.05) versus respective levels measured in WKY controls. The kidneys of SHR-V also contained increased collagen (25+/-2%, P<0.05 using biochemical analysis and 2.4-fold; P<0.01 using quantitative histology). Relaxin treatment significantly normalized collagen content in the LV (P<0.01) and kidney (P<0.05), completely inhibited cell proliferation (P<0.01) and fibroblast differentiation (P<0.05) in the LV, and increased MMP-2 expression (by 25+/-1%; P<0.05) without affecting MMP-9 in the LV compared with that measured in SHR-V. Thus, relaxin is a potent antifibrotic hormone with a rapid-occurring efficacy that may have therapeutic potential for hypertensive disease.
Co-design, co-development, and co-delivery (Co-3D for short) are activities within the co-production research pathway that are increasingly being used in climate change science and adaptation ...projects. However, the research community is still coming to understand how best to incorporate Co-3D in practice, as each project has a specific context around stakeholder relationships, governance arrangements, and capacity to actively participate. This paper outlines five case studies from Australia as examples of different projects engaging with Co-3D in different ways in order to explore how Co-3D is being used and might be improved. Crucially, we include the perceptions and experiences of researchers, funders and end users, as well as our own critical reflections. Each of the projects self-describes as using ‘co-production’, but the extent and format varies widely with different combinations of co-design, co-development and/or co-delivery used in each. Our findings show that without clear understanding of Co-3D within the co-production process, aspects of Co-3D may not be properly considered in planning or implementation. Co-3D activities are not completely distinct, rather they form a continuum of engagement and integration across phases of project work. Thus, the specific definitions and delineations between these terms may not be required for them to be applied. However, practical and explicit negotiation of what ‘co-production’ means in different project contexts is needed so that all parties understand their roles and responsibilities. Further, more evaluations of outcomes and stakeholder experiences are required. We provide seven principles of Co-3D that should be considered when embarking on co-production projects.
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