Pulse wave velocity distribution in a cohort study: from arterial stiffness to early vascular aging

BACKGROUND: By contrast with other southern European people, north Portuguese population registers an especially high prevalence of hypertension and stroke incidence. We designed a cohort study to identify individuals presenting accelerated and premature arterial aging in the Portuguese population. METHOD: Pulse wave velocity (PWV) was measured in randomly sampled population dwellers aged 18-96 years from northern Portugal, and used as a marker of early vascular aging (EVA). Of the 3038 individuals enrolled, 2542 completed the evaluation. RESULTS: Mean PWV value for the entire population was 8.4?m/s (men: 8.6?m/s; women: 8.2?m/s; P??10?m/s). Logistic regression models indicated gender differences concerning the risk of developing large artery damage, with women having the same odds of PWV above 10?m/s 10 years later than men. CONCLUSION: The population PWV values were higher than expected in a low cardiovascular risk area (Portugal). High prevalence rates of EVA and noteworthy large artery damage in young ages were found.Funded by the Life and Health Research Institute, Minho University, Guimarães, Portugal

Temperature-sensitive colloidal phase behavior induced by critical Casimir forces

We report Monte Carlo simulations of phase behavior of colloidal suspensions with near-critical binary solvents using effective pair potentials from experiments. At off-critical solvent composition, the calculated phase diagram agrees well with measurements of the experimental system, indicating that many-body effects are limited. Close to the critical composition, however, agreement between experiment and simulation becomes poorer, signaling the increased importance of many-body effects. Both at and off the critical solvent concentration, the colloidal phase diagram is qualitatively similar to those of molecular systems and obeys the principle of corresponding states with one striking difference: it occurs in a narrow temperature interval of <1C below the solvent phase separation temperature.This work was supported by the Foundation for Fundamental Research on Matter (FOM). P. S. acknowledges support from the Innovational Research Incentives Scheme (VIDI grant) of the Netherlands Organization for Scientific Research (NWO). A. V. V. acknowledges financial support by the Department of Theory and Bio-Systems at the Max Planck Institute of Colloids and Interfaces. We thank A. Maciolek and D. T. F. Mohry for helpful discussions

Quantitative analysis of high-resolution microendoscopic images for diagnosis of neoplasia in patients with Barrett’s esophagus

Background and Aims: Previous studies show that microendoscopic images can be interpreted visually to identify the presence of neoplasia in patients with Barrett’s esophagus (BE), but this approach is subjective and requires clinical expertise. This study describes an approach for quantitative image analysis of microendoscopic images to identify neoplastic lesions in patients with BE. Methods: Images were acquired from 230 sites from 58 patients by using a fiberoptic high-resolution microendoscope during standard endoscopic procedures. Images were analyzed by a fully automated image processing algorithm, which automatically selected a region of interest and calculated quantitative image features. Image features were used to develop an algorithm to identify the presence of neoplasia; results were compared with a histopathology diagnosis. Results: A sequential classification algorithm that used image features related to glandular and cellular morphology resulted in a sensitivity of 84% and a specificity of 85%. Applying the algorithm to an independent validation set resulted in a sensitivity of 88% and a specificity of 85%. Conclusions: This pilot study demonstrates that automated analysis of microendoscopic images can provide an objective, quantitative framework to assist clinicians in evaluating esophageal lesions from patients with BE. (Clinical trial registration number: NCT01384227 and NCT02018367.

The Nature of Composite LINER/HII Galaxies, As Revealed from High-Resolution VLA Observations

A sample of 37 nearby galaxies displaying composite LINER/HII and pure HII spectra was observed with the VLA in an investigation of the nature of their weak radio emission. The resulting radio contour maps overlaid on optical galaxy images are presented here, together with an extensive literature list and discussion of the individual galaxies. Radio morphological data permit assessment of the ``classical AGN'' contribution to the global activity observed in these ``transition'' LINER galaxies. One in five of the latter objects display clear AGN characteristics: these occur exclusively in bulge-dominated hosts.Comment: 31 pages, 27 figures, accepted by ApJ

The Radio Properties of Composite LINER/HII Galaxies

Arcsec-resolution VLA observations -- newly obtained as well as published -- of 40 nearby galaxies are discussed, completing a study of the radio properties of a magnitude-limited sample of nearby galaxies of the composite LINER/HII type. Our results reveal an overall detection rate of at least 25% AGN candidates among these composite sources. The general properties of these AGN candidates, as compared to non-AGN composite sources and HII galaxies, are discussed.Comment: Accepted for publication in ApJ

Treatment-resistant major depressive disorder: Canadian expert consensus on definition and assessment

Background: Treatment-resistant depression (TRD) is a debilitating chronic mental illness that confers increased morbidity and mortality, decreases the quality of life, impairs occupational, social, and offspring development, and translates into increased costs on the healthcare system. The goal of this study is to reach an agreement on the concept, definition, staging model, and assessment of TRD. Methods: This study involved a review of the literature and a modified Delphi process for consensus agreement. The Appraisal of Guidelines for Research & Evaluation II guidelines were followed for the literature appraisal. Literature was assessed for quality and strength of evidence using the grading, assessment, development, and evaluations system. Canadian national experts in depression were invited for the modified Delphi process based on their prior clinical and research expertize. Survey items were considered to have reached a consensus if 80% or more of the experts supported the statement. Results: Fourteen Canadian experts were recruited for three rounds of surveys to reach a consensus on a total of 27 items. Experts agreed that a dimensional definition for treatment resistance was a useful concept to describe the heterogeneity of this illness. The use of staging models and clinical scales was recommended in evaluating depression. Risk factors and comorbidities were identified as potential predictors for treatment resistance. Conclusions: TRD is a meaningful concept both for clinical practice and research. An operational definition for TRD will allow for opportunities to improve the validity of predictors and therapeutic options for these patients

Regulation of cardiac ryanodine receptor function by the cyclic-GMP dependent protein kinase G

Background: The cGMP-dependent protein kinase G (PKG) phosphorylates the cardiac ryanodine receptor (RyR2) in vitro. We aimed to determine whether modulation of endogenous PKG alters RyR2-mediated spontaneous Ca2+ release and whether this effect is linked to a change in RyR2 phosphorylation. Methods: & Results: Human embryonic kidney (HEK293) cells with inducible RyR2 expression were treated with the cGMP analogue 8-Br-cGMP (100 μM) to activate endogenous PKG. In cells transfected with luminal Ca2+ sensor, D1ER, PKG activation significantly reduced the threshold for RyR2-mediated spontaneous Ca2+ release (93.9 ± 0.4% of store size with vehicle vs. 91.7 ± 0.8% with 8-Br-cGMP, P = 0.04). Mutation of the proposed PKG phosphorylation sites, S2808 and S2030, either individually or as a combination, prevented the decrease in Ca2+ release threshold induced by endogenous PKG activation. Interestingly, despite a functional dependence on expression of RyR2 phosphorylation sites, 8-Br-cGMP activation of PKG did not promote a detectable change in S2808 phosphorylation (P = 0.9). Paradoxically, pharmacological inhibition of PKG with KT 5823 (1 μM) also reduced the threshold for spontaneous Ca2+ release through RyR2 without affecting S2808 phosphorylation. Silencing RNA knockdown of endogenous PKG expression also had no quantifiable effect on RyR2 S2808 phosphorylation (P = 0.9). However, unlike PKG inhibition with KT 5823, PKG knockdown did not alter spontaneous Ca2+ release propensity or luminal Ca2+ handling. Conclusion: In an intact cell model, activation of endogenous PKG reduces the threshold for RyR2-mediated spontaneous Ca2+ release in a manner dependent on the RyR2 phosphorylation sites S2808 and S2030. This study clarifies the regulation of RyR2 Ca2+ release by endogenous PKG and functionally implicates the role of RyR2 phosphorylation.Fil: Gonano, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. University of Otago; Nueva ZelandaFil: Aitken Buck, Hamish M.. University of Otago; Nueva ZelandaFil: Chakraborty, Akash D.. University of Otago; Nueva ZelandaFil: Worthington, Luke P. I.. University of Otago; Nueva ZelandaFil: Cully, Tanya R.. University of Otago; Nueva ZelandaFil: Lamberts, Regis R.. University of Otago; Nueva ZelandaFil: Vila Petroff, Martin Gerarde. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Jones, Peter P.. University of Otago; Nueva Zeland

Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

BACKGROUND: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. METHODS: In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. RESULTS: Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. CONCLUSIONS: Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials