Long-term (10 years) prognostic value of a normal thallium-201 myocardial exercise scintigraphy in patients with coronary artery disease documented by angiography

In order to assess the prognostic significance of normal exercise thallium-210 myocardial scintigraphy in patients with documented coronary artery disease, we studied the incidence of cardiac death and non-fatal myocardial infarction in 69 symptomatic patients without prior Q wave myocardial infarction, who demonstrated one or more significant coronary lesions (stenosis ≤70%) on an angiogram performed within 3 months of scintigraphy (Group 1). These patients were compared to a second group of 136 patients with an abnormal exercise scintigram, defined by the presence of reversible defect(s) and angiographically proven coronary artery disease (Group 2), and to a third group of 102 patients with normal exercise scintigraphy without significant coronary lesions (stenosis ≥30%) or with normal coronary angiography (Group 3). In contrast to coronary lesions observed in Group 2, patients in Group I presented more frequently with single- vessel disease (83% vs 35%, P>0·0001) and with more distal lesions (55% vs 23%, P>0·0001). Over a mean follow-up period of 8·6 years, one fatal and eight non-fatal cases of myocardial infarction were observed in Group 1. The majority of patients in Group 1 were treated medically: only 24 (35%) underwent myocardial revascularization, usually by coronary angioplasty. There was no significant difference in the incidence of combined major cardiac events (cardiac death, non-fatal myocardial infarction) in patients with normal exercise scintigraphy, with or without documented coronary artery disease (Groups 1 and 3), while the incidence was higher in Group 2. However, while the mortality remained very low in Group 1, the incidence of non-fatal myocardial infraction was not different from that of Group 2, where most patients underwent revascularization procedures. In conclusion, patients with coronary artery disease and a normal exercise thallium-201 myocardial scintigram usually have mild coronary lesions (single-vessel disease, distal location) and good long-term prognosis, with a low incidence of cardiac deat

Meningeal defects alter the tangential migration of cortical interneurons in Foxc1hith/hith mice

<p>Abstract</p> <p>Background</p> <p>Tangential migration presents the primary mode of migration of cortical interneurons translocating into the cerebral cortex from subpallial domains. This migration takes place in multiple streams with the most superficial one located in the cortical marginal zone. While a number of forebrain-expressed molecules regulating this process have emerged, it remains unclear to what extent structures outside the brain, like the forebrain meninges, are involved.</p> <p>Results</p> <p>We studied a unique <it>Foxc1 </it>hypomorph mouse model (<it>Foxc1^hith/hith</it>) with meningeal defects and impaired tangential migration of cortical interneurons. We identified a territorial correlation between meningeal defects and disruption of interneuron migration along the adjacent marginal zone in these animals, suggesting that impaired meningeal integrity might be the primary cause for the observed migration defects. Moreover, we postulate that the meningeal factor regulating tangential migration that is affected in homozygote mutants is the chemokine Cxcl12. In addition, by using chromatin immunoprecipitation analysis, we provide evidence that the <it>Cxcl12 </it>gene is a direct transcriptional target of Foxc1 in the meninges. Further, we observe migration defects of a lesser degree in Cajal-Retzius cells migrating within the cortical marginal zone, indicating a less important role for Cxcl12 in their migration. Finally, the developmental migration defects observed in <it>Foxc1^hith/hith</it>mutants do not lead to obvious differences in interneuron distribution in the adult if compared to control animals.</p> <p>Conclusions</p> <p>Our results suggest a critical role for the forebrain meninges to promote during development the tangential migration of cortical interneurons along the cortical marginal zone and Cxcl12 as the factor responsible for this property.</p

Enantiospecific pharmacokinetics of intravenous dexmedetomidine in beagles

The goal of this study was to investigate the pharmacokinetic (PK) behaviour of dexmedetomidine in dogs administered as a pure enantiomer versus as part of a racemic mixture. Eight unmedicated intact purpose-bread beagles were included. Two intravenous treatments of either medetomidine or dexmedetomidine were administered at 10- to 14-day intervals. Atipamezole or saline solution was administered intramuscularly 45&nbsp;min later. Venous blood samples were collected into EDTA collection tubes, and the quantification of dexmedetomidine and levomedetomidine was performed by chiral LC–MS/MS. All dogs appeared sedated after each treatment without complication. Plasma concentrations of levomedetomidine were measured only in the racemic group and were 51.4% (51.4%–56.1%) lower than dexmedetomidine. Non-compartmental analysis (NCA) was performed for both drugs, while dexmedetomidine data were further described using a population pharmacokinetic approach. A standard two-compartment mammillary model with linear elimination with combined additive and multiplicative error model for residual unexplained variability was established for dexmedetomidine. An exponential model was finally retained to describe inter-individual variability on parameters of clearance (Cl1) and central and peripheral volumes of distribution (V1, V2). No effect of occurrence, levomedetomidine or atipamezole could be observed on dexmedetomidine PK parameters. Dexmedetomidine did not undergo significantly different PK when administered alone or as part of the racemic mixture in otherwise unmedicated dogs

Foxc1 is required by pericytes during fetal brain angiogenesis

Summary Brain pericytes play a critical role in blood vessel stability and blood–brain barrier maturation. Despite this, how brain pericytes function in these different capacities is only beginning to be understood. Here we show that the forkhead transcription factor Foxc1 is expressed by brain pericytes during development and is critical for pericyte regulation of vascular development in the fetal brain. Conditional deletion of Foxc1 from pericytes and vascular smooth muscle cells leads to late-gestation cerebral micro-hemorrhages as well as pericyte and endothelial cell hyperplasia due to increased proliferation of both cell types. Conditional Foxc1 mutants do not have widespread defects in BBB maturation, though focal breakdown of BBB integrity is observed in large, dysplastic vessels. qPCR profiling of brain microvessels isolated from conditional mutants showed alterations in pericyte-expressed proteoglycans while other genes previously implicated in pericyte–endothelial cell interactions were unchanged. Collectively these data point towards an important role for Foxc1 in certain brain pericyte functions (e.g. vessel morphogenesis) but not others (e.g. barriergenesis)

Major Differences in Diet across Three Linguistic Regions of Switzerland: Results from the First National Nutrition Survey menuCH.

Switzerland is a multilingual country located between Germany, France and Italy, which differ by dietary habits and related outcomes. We explored differences in food consumption as well as compliance to the Swiss food-based dietary guidelines (FBDG) across the German-, French-, and Italian-speaking regions. The 2014-2015 nationwide cross-sectional survey was conducted among a stratified random sample of 2057 adults aged 18 to 75 years. Trained dietitians assessed food consumption via two non-consecutive 24-h dietary recalls using the international validated software GloboDiet &lt;sup&gt;®&lt;/sup&gt; . Recorded foods and beverages were classified into six groups and 31 subgroups relevant for assessing compliance to the FBDG (Swiss Food Pyramid). Usual daily intake distributions were modelled and weighted for sampling design, non-response, weekdays and season. Participation rate was 38%. Significant differences across regions were observed in 18 of 31 food subgroups ( &lt;i&gt;p&lt;/i&gt; ≤ 0.01). Weighted mean daily intakes in the German-, French- and Italian-speaking regions were, respectively, 245 g, 155 g, 140 g for soft drinks, 273 g, 214 g, 135 g for coffee, 127 g, 72 g, 109 g for milk, 32 g, 45 g, 43 g for red meat, 18 g, 29 g, 34 g for fish/seafood, 8.1 g, 6.4 g, 3.7 g for butter, and 206 g, 214 g, 168 g for vegetables. The seven FBDGs were followed by &lt;1% of the population. Four in 10 participants met ≥3 FBDG. Eighteen percent of participants ate ≥5 portions of fruit and vegetables a day, without regional differences. Food consumption substantially differed across the three linguistic regions of Switzerland. Adherence to FBDG was uniformly low. This highlights the potential influence of culture on diet. Nutritional education along with public health interventions are needed and may be most efficient if regionally targeted

Retinoic Acid Regulates Endothelial β-catenin Expression and Pericyte Numbers in the Developing Brain Vasculature

The acquisition of brain vascular properties, like tight junctions and pericytes, to form the blood-brain barrier (BBB) is crucial for a properly functioning central nervous system (CNS). Endothelial WNT signaling is a known driver of brain vascular development and BBB properties, however, it is unclear how endothelial WNT signaling is regulated. We recently showed that mouse embryos with disruptions in endothelial retinoic acid (RA) signaling have ectopic WNT signaling in the brain vasculature. Using immunohistochemistical analysis, we show that increased vascular WNT signaling in RA mutants (Pdgfbicre; dnRAR403-flox and Rdh10 mutants) is associated with elevated expression of the WNT transcriptional effector, β-catenin, in the brain endothelium. In vitro immunocytochemistry and proximity ligation studies in brain endothelial cells reveal that RA, through its receptor RARα, regulates β-catenin expression in brain endothelial cells via transcriptional suppression and phosphorylation events that targets β-catenin for proteasomal degradation, the latter dependent on PKCα. We find that one function of RA in regulating vascular WNT signaling is to modulate the pericyte numbers in the developing brain vasculature. RA-mediated regulation of vascular WNT signaling could be needed to prevent over-recruitment of pericytes that might impair endothelial-pericyte interactions crucial for vascular stability

Does compulsory voting increase support for leftist policy?

Citizens unequally participate in referendums, and this may systematically bias policy in favor of those who vote. Some view compulsory voting as an important tool to alleviate this problem, whereas others worry about its detrimental effects on the legitimacy and quality of democratic decision making. So far, however, we lack systematic knowledge about the causal effect of compulsory voting on public policy. We argue that sanctioned compulsory voting mobilizes citizens at the bottom of the income distribution and that this translates into an increase in support for leftist policies. We empirically explore the effects of a sanctioned compulsory voting law on direct-democratic decision making in Switzerland. We find that compulsory voting significantly increases electoral support for leftist policy positions in referendums by up to 20 percentage points. We discuss the implications of these results for our understanding of the policy consequences of electoral institutions

Introduction: Re-imagining Cities in Africa

The introduction presents the key concepts and core arguments of this special issue Re-Imagining African Cities: The Arts and Urban Politics that results from a workshop hosted by the Visual Culture Research Group at the Department of Anthropology, University of Basel, in 2016. Summarising and presenting the essays, it offers insights into how urban imagination and the physical cities interrelate in urban aesthetic practices. How do artists articulate their experiences and observations of the city? What position and relevance do the material city, the city image and the urban imagination have in the practice of these visual and performing artists? How does their work relate to the urban as a social space on the one hand and as an imagined entity on the other? The African and diasporic cities of Kinshasa, Paris, Cape Town, Lagos, Bamenda, Freetown, Johannesburg and Kampala are both the sites and research subjects of the authors and of the artists they present. The focus on visual and performative arts provides the vehicle and the critical means of observing, articulating and representing these entanglements of the material cities, their images and their societal as well as artistic imagination

Role of fatty acid transporters in epidermis: Implications for health and disease

Skin epidermis is an active site of lipid synthesis. The intercellular lipids of human stratum corneum (SC) are unique in composition and quite different from the lipids found in most biological membranes. The three major lipids in the SC are free fatty acids, cholesterol and ceramides. Fatty acids can be synthesized by keratinocytes de novo and, in addition, need to be taken up from the circulation. The latter process has been shown to be protein mediated, and several fatty acid transporters are expressed in skin. Recent studies of transgenic and knockout animal models for fatty acid transporters and the identification of fatty acid transport protein 4 (FATP4 or SLC27A4) mutations as causative for Ichthyosis Prematurity Syndrome highlight the vital roles of fatty acid transport and metabolism in skin homeostasis. This review provides an overview of our current understanding of the role of fatty acids and their transporters in cutaneous biology, including their involvement in epidermal barrier generation and skin inflammation

Cryptographic properties of Boolean functions defining elementary cellular automata

In this work, the algebraic properties of the local transition functions of elementary cellular automata (ECA) were analysed. Specifically, a classification of such cellular automata was done according to their algebraic degree, the balancedness, the resiliency, nonlinearity, the propagation criterion and the existence of non-zero linear structures. It is shown that there is not any ECA satisfying all properties at the same time