Completely contractive projections on operator algebras

The main goal of this paper is to find operator algebra variants of certain deep results of Stormer, Friedman and Russo, Choi and Effros, Effros and Stormer, Robertson and Youngson, Youngson, and others, concerning projections on C*-algebras and their ranges. (See papers of these authors referenced in the bibliography.) In particular we investigate the `bicontractive projection problem' and related questions in the category of operator algebras. To do this, we will add the ingredient of `real positivity' from recent papers of the first author with Read.Comment: To appear Pacific J Math; several corrections and small improvements. Keywords Operator algebra, completely contractive map, projection, conditional expectation, bicontractive projection, real positive, noncommutative Banach-Stone theore

Hyperosmolarity potentiates toxic effects of benzalkonium chloride on conjunctival epithelial cells in vitro

International audiencePurpose: Benzalkonium chloride (BAK), the most commonly used preservative in eye drops, is known to induce ocular irritation symptoms and dry eye in long-term treated patients and animal models. As tear film hyperosmolarity is diagnostic of some types of dry eye disease, we determined in vitro on conjunctival epithelial cells the cytoxicity of BAK in hyperosmolar conditions through cell viability, apoptosis, and oxidative stress assays.Methods: The Wong Kilbourne derivative of Chang conjunctival epithelial cells were cultured for 24 h or 48 h either in NaCl-induced hyperosmolar conditions (400–425–500 mOsM), in low concentrations of BAK (10−4%, 3.10−4%, and 5.10−4%), or in combination of both. We investigated cell viability through lysosomal integrity evaluation, cell death (cell membrane permeability and chromatin condensation), and oxidative stress (reactive oxygen species, superoxide anion) using spectrofluorimetry. Immunohistochemistry was performed for cytoskeleton shrinkage (phalloidin staining), mitochondrial permeability transition pore (cytochrome c release), the apoptosis effector active caspase-3, and the caspase-independent apoptosis factor AIF. We also observed early effects induced by the experimental conditions on the conjunctival cell layers using phase contrast imaging of live cells.Results: As compared to standard culture solutions, hyperosmolar stress potentiated BAK cytotoxicity on conjunctival cells through the induction of oxidative stress; reduction of cell viability; cell membrane permeability increase; cell shrinkage with cell blebbing, as shown in phase contrast imaging of live cells; and chromatin condensation. Like BAK, but to a much lesser extent, hyperosmolarity increased cell death in a concentration-dependent manner through a caspase-dependent apoptosis characterized by a release of cytochrome c in the cytoplasm from mitochondria and the activation of caspase-3. Moreover, the caspase-independent apoptosis factor AIF was found translocated from mitochondria to the nucleus in both conditions.Conclusions: This study showed increased cytotoxic effects of BAK in hyperosmotic conditions, with characteristic cell death processes, namely caspase-dependent and independent apoptosis and oxidative stress. As BAK is known to disrupt tear film, which could promote evaporative dry eye and tear hyperosmolarity, BAK could promote the conditions enhancing its own cytotoxicity. This in vitro hyperosmolarity model thus highlights the risk of inducing a vicious cycle and the importance of avoiding BAK in patients with dry eye conditions

Effect of a Mobile Phone Intervention on Quitting Smoking in a Young Adult Population of Smokers: Randomized Controlled Trial

This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR mhealth and uhealth, is properly cited. The complete bibliographic information, a link to the original publication on http://mhealth.jmir.org/, as well as this copyright and license information must be included.Background: Digital mobile technology presents a promising medium for reaching young adults with smoking cessation interventions because they are the heaviest users of this technology. Objective: The aim of this study was to determine the efficacy of an evidence-informed smartphone app for smoking cessation, Crush the Crave (CTC), on reducing smoking prevalence among young adult smokers in comparison with an evidence-informed self-help guide, On the Road to Quitting (OnRQ). Methods: A parallel, double-blind, randomized controlled trial with 2 arms was conducted in Canada to evaluate CTC. In total, 1599 young adult smokers (aged 19 to 29 years) intending to quit smoking in the next 30 days were recruited online and randomized to receive CTC or the control condition OnRQ for a period of 6 months. The primary outcome measure was self-reported continuous abstinence at the 6-month follow-up. Results: Overall follow-up rates were 57.41% (918/1599) and 60.48% (967/1599) at 3 and 6 months, respectively. Moreover, 45.34% (725/1599) of participants completed baseline, 3-, and 6-month follow-up. Intention-to-treat analysis (last observation carried forward) showed that continuous abstinence (N=1599) at 6 months was not significantly different at 7.8% (64/820) for CTC versus 9.2% (72/779) for OnRQ (odds ratio; OR 0.83, 95% CI 0.59-1.18). Similarly, 30-day point prevalence abstinence at 6 months was not significantly different at 14.4% (118/820) and 16.9% (132/779) for CTC and OnRQ, respectively (OR 0.82, 95% CI 0.63-1.08). However, these rates of abstinence were favorable compared with unassisted 30-day quit rates of 11.5% among young adults. Secondary measures of quit attempts and the number of cigarettes smoked per day at 6-month follow-up did not reveal any significant differences between groups. For those who completed the 6-month follow-up, 85.1% (359/422) of young adult smokers downloaded CTC as compared with 81.8% (346/423) of OnRQ, χ21(N=845)=1.6, P=.23. Furthermore, OnRQ participants reported significantly higher levels of overall satisfaction (mean 3.3 [SD 1.1] vs mean 2.6 [SD 1.3]; t644=6.87, P<.001), perceived helpfulness (mean 5.8 [SD 2.4] vs mean 4.3 [SD 2.6], t657=8.0, P<.001), and frequency of use (mean 3.6 [SD 1.2] vs mean 3.2 [SD 1.1], t683=5.7, P<.001) compared with CTC participants. Conclusions: CTC was feasible for delivering cessation support but was not superior to a self-help guide in helping motivated young adults to quit smoking. CTC will benefit from further formative research to address satisfaction and usage. As smartphone apps may not serve as useful alternatives to printed self-help guides, there is a need to conduct further research to understand how digital mobile technology smoking cessation interventions for smoking cessation can be improved. Trial Registration: ClinicalTrials.gov NCT01983150; http://clinicaltrials.gov/ct2/show/NCT01983150 (Archived by WebCite at http://www.webcitation.org/6VGyc0W0i)This work was supported by a grant from Health Canada, Federal Tobacco Control Strategy (Agreement #: 6549-15-2011/8300125) and a grant from the Canadian Institutes of Health Research (Grant #: MOP-130303). NBB received salary support from the Canadian Cancer Society Research Institute (Grant #: 2011-701019 & Grant# 2017-704507)

The Chemokine CCL2 Protects Against Methylmercury Neurotoxicity

Industrial pollution due to heavy metals such as mercury is a major concern for the environment and public health. Mercury, in particular methylmercury (MeHg), primarily affects brain development and neuronal activity, resulting in neurotoxic effects. Because chemokines can modulate brain functions and are involved in neuroinflammatory and neurodegenerative diseases, we tested the possibility that the neurotoxic effect of MeHg may interfere with the chemokine CCL2. We have used an original protocol in young mice using a MeHg-contaminated fish-based diet for 3 months relevant to human MeHg contamination. We observed that MeHg induced in the mice cortex a decrease in CCL2 concentrations, neuronal cell death, and microglial activation. Knock-out (KO) CCL2 mice fed with a vegetal control food already presented a decrease in cortical neuronal cell density in comparison with wild-type animals under similar diet conditions, suggesting that the presence of CCL2 is required for normal neuronal survival. Moreover, KO CCL2 mice showed a pronounced neuronal cell death in response to MeHg. Using in vitro experiments on pure rat cortical neurons in culture, we observed by blockade of the CCL2/CCR2 neurotransmission an increased neuronal cell death in response to MeHg neurotoxicity. Furthermore, we showed that sod genes are upregulated in brain of wild-type mice fed with MeHg in contrast to KO CCL2 mice and that CCL2 can blunt in vitro the decrease in glutathione levels induced by MeHg. These original findings demonstrate that CCL2 may act as a neuroprotective alarm system in brain deficits due to MeHg intoxicatio

Lymphatic and Immune Cell Cross-Talk Regulates Cardiac Recovery After Experimental Myocardial Infarction

Objective: Lymphatics play an essential pathophysiological role in promoting fluid and immune cell tissue clearance. Conversely, immune cells may influence lymphatic function and remodeling. Recently, cardiac lymphangiogenesis has been proposed as a therapeutic target to prevent heart failure after myocardial infarction (MI). We investigated the effects of gene therapy to modulate cardiac lymphangiogenesis post-MI in rodents. Second, we determined the impact of cardiac-infiltrating T cells on lymphatic remodeling in the heart. Approach and Results: Comparing adenoviral versus adeno-associated viral gene delivery in mice, we found that only sustained VEGF (vascular endothelial growth factor)-C(C156S)therapy, achieved by adeno-associated viral vectors, increased cardiac lymphangiogenesis, and led to reduced cardiac inflammation and dysfunction by 3 weeks post-MI. Conversely, inhibition of VEGF-C/-D signaling, through adeno-associated viral delivery of soluble VEGFR3 (vascular endothelial growth factor receptor 3), limited infarct lymphangiogenesis. Unexpectedly, this treatment improved cardiac function post-MI in both mice and rats, linked to reduced infarct thinning due to acute suppression of T-cell infiltration. Finally, using pharmacological, genetic, and antibody-mediated prevention of cardiac T-cell recruitment in mice, we discovered that both CD4(+)and CD8(+)T cells potently suppress, in part through interferon-gamma, cardiac lymphangiogenesis post-MI. Conclusions: We show that resolution of cardiac inflammation after MI may be accelerated by therapeutic lymphangiogenesis based on adeno-associated viral gene delivery of VEGF-C-C156S. Conversely, our work uncovers a major negative role of cardiac-recruited T cells on lymphatic remodeling. Our results give new insight into the interconnection between immune cells and lymphatics in orchestration of cardiac repair after injury.Peer reviewe

Additive scales in degenerative disease - calculation of effect sizes and clinical judgment

<p>Abstract</p> <p>Background</p> <p>The therapeutic efficacy of an intervention is often assessed in clinical trials by scales measuring multiple diverse activities that are added to produce a cumulative global score. Medical communities and health care systems subsequently use these data to calculate pooled effect sizes to compare treatments. This is done because major doubt has been cast over the clinical relevance of statistically significant findings relying on <it>p </it>values with the potential to report chance findings. Hence in an aim to overcome this pooling the results of clinical studies into a meta-analyses with a statistical calculus has been assumed to be a more definitive way of deciding of efficacy.</p> <p>Methods</p> <p>We simulate the therapeutic effects as measured with additive scales in patient cohorts with different disease severity and assess the limitations of an effect size calculation of additive scales which are proven mathematically.</p> <p>Results</p> <p>We demonstrate that the major problem, which cannot be overcome by current numerical methods, is the complex nature and neurobiological foundation of clinical psychiatric endpoints in particular and additive scales in general. This is particularly relevant for endpoints used in dementia research. 'Cognition' is composed of functions such as memory, attention, orientation and many more. These individual functions decline in varied and non-linear ways. Here we demonstrate that with progressive diseases cumulative values from multidimensional scales are subject to distortion by the limitations of the additive scale. The non-linearity of the decline of function impedes the calculation of effect sizes based on cumulative values from these multidimensional scales.</p> <p>Conclusions</p> <p>Statistical analysis needs to be guided by boundaries of the biological condition. Alternatively, we suggest a different approach avoiding the error imposed by over-analysis of cumulative global scores from additive scales.</p