Background. Several studies have shown antifibrotic effects of angiotensin converting enzyme (ACE) inhibitors as well as of angiotensin receptor 1 (AT1) antagonists, however, prospective trials with ...clinical end points comparing these effects do not exist. COL4A3−/− mice develop a non-hypertensive progressive renal fibrosis. We used this animal model to compare the potential of ACE inhibitor vs AT1 antagonist to prevent renal fibrosis irrespective of blood pressure-dependent involvement by the renin system. Methods. COL4A3−/− mice were treated with placebo, ramipril or candesartan. Blood pressure, proteinuria, serum urea and lifespan were monitored. Renal matrix was characterized by immuno-histochemistry, light and electron microscopy. Further biochemical analysis was provided using cDNA microarray and western blot techniques. Results. Untreated mice died of renal failure after 71±6 days. Ramipril and candesartan both delayed onset and reduced the extent of proteinuria. Both had minor effects on blood pressure and postponed onset of uraemia. Ramipril increased lifespan by 111% to 150±21 days (P<0.01), whereas candesartan resulted in only a 38% prolongation to 98±16 days (P<0.01). Ramipril reduced glomerular and tubulo-interstitial fibrosis and numbers of activated fibroblasts to a greater extent than candesartan. Microarray and western blot analysis revealed a higher antifibrotic potential of ramipril in terms of downregulation of TGFβ, connective tissue growth factor, metalloproteinases and extracellular matrix proteins. Conclusions. The results indicate an antifibrotic, nephroprotective effect of ACE inhibitors and AT1 antagonists in an animal model of progressive renal fibrosis. The greater antifibrotic effect of ramipril at the maximal therapeutic doses employed may not be explained by different antiproteinuric or blood pressure lowering properties, but by—in contrast to candesartan—its ability to hinder the proinflammatory, profibrotic activation of the angiotensin receptor 2.
Background. Alport syndrome is caused by mutations in genes encoding for the α3, α4 or α5 chain of type IV collagen leading to excessive production of fibrotic tissue and end-stage renal failure. ...HMG-CoA-reductase-inhibitors exhibit pleiotropic effects by which they modulate the production of connective tissue. The aim of this study was to examine the anti-fibrotic effect of the HMG-CoA-reductase-inhibitor, cerivastatin, in COL4A3 knockout mice, an animal model of Alport syndrome with progressive renal fibrosis. Methods. Forty homozygous COL4A3 knockout mice received cerivastatin, starting 28 or 49 days after birth. Mice were sacrificed at day 52 or 66 after birth. Immunohistochemistry against laminin and fibronectin was performed. Inflammatory cell infiltration was determined by F4/80- and CD3-staining. Myofibroblasts were identified by an α-smooth muscle actin staining. Expression of the profibrotic cytokines, TGF-β1 and CTGF, were determined by immunoblot. Results. The lifespan of treated COL4A3 knockout mice was increased by 28% compared with untreated animals (71 ± 6 vs 91 ± 9 days, P < 0.01). Early cerivastatin treatment reduced cholesterol levels (113 ± 13 vs 141 ± 19 mmol/l in untreated animals, P < 0.05) and serum urea (164 vs 235 mmol/l, day 66, P < 0.05). Treatment also decreased proteinuria (5.5 vs 12 g/l at day 66, P < 0.05). Deposition of laminin and fibronectin, expression of TGF-β and CTGF was reduced. Infiltration of T-cells and macrophages as well as myofibroblasts appeared to be reduced in kidneys from cerivastatin-treated mice. Conclusion. Cerivastatin prolongs the lifespan of COL4A3 knockout mice, reduces proteinuria and delays uraemia. These effects are associated with decreased renal fibrosis and a reduction of inflammatory cell infiltration.
Abstract
The current study investigated college students' experiences of a gamified informatics course. We surveyed 139 students aged 18–31 years (
M
= 20 years,
SD
= 1.5) enrolled in an ...undergraduate informatics course focused on social networking technologies. Surveys were conducted at 3 time points during the course (beginning, middle, and end). Overall, we found positive trends with respect to students' perceptions of gamification's impact on their learning, achievement, and engagement in the course material. Although students who played and identified variously with recreational games were more alike than not, we did uncover one notable difference with respect to how students' gaming frequency impacted their engagement in the course. Nongamers expressed somewhat less motivation to do well in the course than frequent gamers. For all other measures of engagement, however, nongamers appeared to be equally engaged by the gamified format of the course as gamers. There were virtually no differences between male and female students' perceptions of gamification. This study contributes new insight into the conditions under which gamification succeeds or fails in educational settings. These insights will be useful to designers and instructors of gamified learning environments as they seek to engage and support a variety of learners.
Lay Description
What is already known about this topic:
Several studies show positive effects of gamification on student achievement, engagement, and motivation.
Fewer studies show mixed or negative effects on student achievement, engagement, and motivation.
Few studies probe how different types of students respond to gamified learning experiences.
What this paper adds:
New insight into the conditions under which gamification succeeds or fails in educational settings.
Gamers and nongamers were more alike than not in their response to gamification.
Nongamers were somewhat less motivated to succeed in the course than gamers.
No significant gender differences were found.
Implications for practice and/or policy:
Gamification can be an effective way to engage university students, regardless of their gender or prior experiences with gaming.
Abstract
Funding Acknowledgements
Type of funding sources: Private hospital(s). Main funding source(s): Mayo Clinic
Background/Introduction
Syncope is a common presentation in heart failure (HF) ...patients. However, the associations between syncope and prognosis in HF patients with the cardiac implantable electronic device (CIED) have not been demonstrated. It is unclear whether syncope increases all-cause mortality in HF patients with CIED.
Purpose
We aimed to examine the association between syncope and all-cause mortality in the largest cohort of HF with reduced ejection fraction (HFrEF), mid-ranged ejection fraction (HFmEF), and preserved ejection fraction (HFpEF) patients with and without CIED.
Methods
A retrospective cohort of patients with HF and syncope at our hospital between 2010 and 2015 were identified, and 1:1 propensity was matched with a control group of HF patients without syncope. A chart review was conducted. The multivariate Cox regression model was applied to estimate the association between syncope and the all-cause mortality endpoint.
Results
3,449 HF patients were diagnosed with syncope (mean age, 72.8±14.5 years; 41.5% women), and the propensity-matched control HF patients without syncope (n=3,449) aged 72.8±14.3 years, and 42.5% women were selected. Cardiac implantable electronic devices were implanted more in HF patients with syncope (32.5% versus 13.7%, p<0.001). Implantable cardioverter defibrillators were implanted more in HF patients with syncope (15.6% versus 8.3%, p<0.001) as well as pacemakers (16.9% versus 7.5%, p<0.001) and cardiac resynchronization therapy devices (6.9% versus 4.8%, p=0.015). Among HF patients with CIED, syncope significantly increased the risk of all-cause mortality in HFrEF patients (hazard ratio HR=1.479, 95% confidence interval CI: 1.197-1.828, p<0.001) but not in HFpEF (HR=0.980, 95%CI: 0.793-1.210, p=0.849)(Figure 1). Syncope also tended to increase the risk of all-cause mortality in HFmEF patients with CIED but was not significant (HR=1.193, 95%CI: 0.762-1.865, p=0.762)(Figure 1). Among HF patients without CIED, syncope did not increase the risk of all-cause mortality in HFrEF (HR=0.923, 95%CI: 0.806-1.057, p=0.247), HFmEF (HR=1.074, 95%CI: 0.848-1.360, p=0.554), or HFpEF (HR=0.964, 95%CI: 0.883-1.052, p=0.406).
Conclusions
Syncope significantly increased the risk of all-cause mortality in HFrEF patients but not in HFmEF or HFpEF patients with CIED. The association of syncope and increased mortality in HFrEF patients with CIED suggests that syncope may be a marker and a factor of mortality and warrants further investigation.
Ongoing experimental efforts in Antarctica seek to detect ultra-high energy neutrinos by measurement of radio-frequency (RF) Askaryan radiation generated by the collision of a neutrino with an ice ...molecule. An array of RF antennas, deployed either in-ice or in-air, is used to infer the properties of the neutrino. To evaluate their experimental sensitivity, such experiments require a refractive index model for ray tracing radio-wave trajectories from a putative in-ice neutrino interaction point to the receiving antennas; this gives the degree of signal absorption or ray bending from source to receiver. The gradient in the density profile over the upper 200 meters of Antarctic ice, coupled with Fermat's least-time principle, implies ray "bending" and the existence of "forbidden" zones for predominantly horizontal signal propagation at shallow depths. After re-deriving the formulas describing such shadowing, we report on experimental results that, somewhat unexpectedly, demonstrate the existence of electromagnetic wave transport modes from nominally shadowed regions. Finally, the fact that this shadow-signal propagation is observed both at South Pole and the Ross Ice Shelf in Antarctica suggests that the effect may be a generic property of polar ice, with potentially important implications for experiments seeking to detect neutrinos.
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