National income inequality predicts women's preferences for masculinized faces better than health does

This article is available open access through the publisher’s website at the link below. Copyright @ 2010 The Royal Society

Pilot Study to Assess Breathing During Sight-Read Stringed Instrument Performance

For many musicians, one common occurrence during a performance is the presence of stage fright. Stage fright, though not always expressed can influence the confidence and self-esteem of a performer, and thus can affect the quality of the performance. Every day musicians are affected by stage fright, and there has been no exact solution as to how to lessen the feeling of anxiety musicians feel before performing. No data has been collected to find the correlation between the regularity of breathing and the level of stage fright that a person feels during their performance. A way to quantify regularity of breathing could be crucial to enhancing a musician\u27s musical ability, as well as eliminating the discomfort of stage fright during performance. The purpose of this study is to quantitatively assess the regularity of breathing during a sight-read stringed instrument performance, while gaining more insight as to how stage fright is hindering the quality of the performance

Pilot Study to Assess Breathing During Sight-Read Stringed Instrument Performance

For many musicians, one common occurrence during a performance is the presence of stage fright. Stage fright, though not always expressed can influence the confidence and self-esteem of a performer, and thus can affect the quality of the performance. Every day musicians are affected by stage fright, and there has been no exact solution as to how to lessen the feeling of anxiety musicians feel before performing. No data has been collected to find the correlation between the regularity of breathing and the level of stage fright that a person feels during their performance. A way to quantify regularity of breathing could be crucial to enhancing a musician\u27s musical ability, as well as eliminating the discomfort of stage fright during performance. The purpose of this study is to quantitatively assess the regularity of breathing during a sight-read stringed instrument performance, while gaining more insight as to how stage fright is hindering the quality of the performance

Basal protein phosphatase 2A activity restrains cytokine expression: Role for MAPKs and tristetraprolin

PP2A is a master controller of multiple inflammatory signaling pathways. It is a target in asthma; however the molecular mechanisms by which PP2A controls inflammation warrant further investigation. In A549 lung epithelial cells in vitro we show that inhibition of basal PP2A activity by okadaic acid (OA) releases restraint on MAPKs and thereby increases MAPK-mediated pro-asthmatic cytokines, including IL-6 and IL-8. Notably, PP2A inhibition also impacts on the anti-inflammatory protein - tristetraprolin (TTP), a destabilizing RNA binding protein regulated at multiple levels by p38 MAPK. Although PP2A inhibition increases TTP mRNA expression, resultant TTP protein builds up in the hyperphosphorylated inactive form. Thus, when PP2A activity is repressed, pro-inflammatory cytokines increase and anti-inflammatory proteins are rendered inactive. Importantly, these effects can be reversed by the PP2A activators FTY720 and AAL(s), or more specifically by overexpression of the PP2A catalytic subunit (PP2A-C). Moreover, PP2A plays an important role in cytokine expression in cells stimulated with TNFα; as inhibition of PP2A with OA or PP2A-C siRNA results in significant increases in cytokine production. Collectively, these data reveal the molecular mechanisms of PP2A regulation and highlight the potential of boosting the power of endogenous phosphatases as novel anti-inflammatory strategies to combat asthmatic inflammation

Cooling or Warming the Esophagus to Reduce Esophageal Injury During Left Atrial Ablation in the Treatment of Atrial Fibrillation.

Ablation of the left atrium using either radiofrequency (RF) or cryothermal energy is an effective treatment for atrial fibrillation (AF) and is the most frequent type of cardiac ablation procedure performed. Although generally safe, collateral injury to surrounding structures, particularly the esophagus, remains a concern. Cooling or warming the esophagus to counteract the heat from RF ablation, or the cold from cryoablation, is a method that is used to reduce thermal esophageal injury, and there are increasing data to support this approach. This protocol describes the use of a commercially available esophageal temperature management device to cool or warm the esophagus to reduce esophageal injury during left atrial ablation. The temperature management device is powered by standard water-blanket heat exchangers, and is shaped like a standard orogastric tube placed for gastric suctioning and decompression. Water circulates through the device in a closed-loop circuit, transferring heat across the silicone walls of the device, through the esophageal wall. Placement of the device is analogous to the placement of a typical orogastric tube, and temperature is adjusted via the external heat-exchanger console

Subcortical nuclei volumes are associated with cognition in children post-convulsive status epilepticus: Results at nine years follow-up

PURPOSE: The purpose of the present study was to investigate the relationship between subcortical nuclei volume and cognition in children with post-convulsive status epilepticus (CSE). METHODS: Structural T1-weighted magnetic resonance imaging (MRI) scans (Siemens Avanto, 1.5 T) and neuropsychological assessments (full-scale intelligence quotient (FSIQ) and Global Memory Scores (GMS)) were collected from subjects at a mean 8.5 years post-CSE (prolonged febrile seizures (PFS), n = 30; symptomatic/known, n = 28; and other, n = 12) and from age- and sex-matched healthy controls (HC). Subjects with CSE were stratified into those with lower cognitive ability (LCA) (CSE+, n = 22) and those without (CSE-, n = 48). Quantitative volumetric analysis using Functional MRI of the Brain Software Library (FSL) (Analysis Group, FMRIB, Oxford) provided segmented MRI brain volumes. Univariate analysis of covariance (ANCOVA) was performed to compare subcortical nuclei volumes across subgroups. Multivariable linear regression was performed for each subcortical structure and for total subcortical volume (SCV) to identify significant predictors of LCA (FSIQ <85) while adjusting for etiology, age, socioeconomic status, sex, CSE duration, and intracranial volume (ICV); Bonferroni correction was applied for the analysis of individual subcortical nuclei. RESULTS: Seventy subjects (11.8 ± 3.4 standard deviation (SD) years; 34 males) and 72 controls (12.1 ± 3.0SD years; 29 males) underwent analysis. Significantly smaller volumes of the left thalamus, left caudate, right caudate, and SCV were found in subjects with CSE+ compared with HC, after adjustment for intracranial, gray matter (GM), or cortical/cerebellar volume. When compared with subjects with CSE-, subjects with CSE+ also had smaller volumes of the left thalamus, left pallidum, right pallidum, and SCV. Individual subcortical nuclei were not associated, but SCV was associated with FSIQ (p = 0.005) and GMS (p = 0.014). Intracranial volume and etiology were similarly predictive. CONCLUSIONS: Nine years post-CSE, SCV is significantly lower in children who have LCA compared with those that do not. However, in this cohort, we are unable to determine whether the relationship is independent of ICV or etiology. Future, larger scale studies may help tease this out

Activating protein phosphatase 2A (PP2A) enhances tristetraprolin (TTP) anti-inflammatory function in A549 lung epithelial cells

© 2016. Chronic respiratory diseases are driven by inflammation, but some clinical conditions (severe asthma, COPD) are refractory to conventional anti-inflammatory therapies. Thus, novel anti-inflammatory strategies are necessary. The mRNA destabilizing protein, tristetraprolin (TTP), is an anti-inflammatory molecule that functions to induce mRNA decay of cytokines that drive pathogenesis of respiratory disorders. TTP is regulated by phosphorylation and protein phosphatase 2A (PP2A) is responsible for dephosphorylating (and hence activating) TTP, amongst other targets. PP2A is activated by small molecules, FTY720 and AAL(S), and in this study we examine whether these compounds repress cytokine production in a cellular model of airway inflammation using A549 lung epithelial cells stimulated with tumor necrosis factor α (TNFα) in vitro. PP2A activators significantly increase TNFα-induced PP2A activity and inhibit mRNA expression and protein secretion of interleukin 8 (IL-8) and IL-6; two key pro-inflammatory cytokines implicated in respiratory disease and TTP targets. The effect of PP2A activators is not via an increase in TNFα-induced TTP mRNA expression; instead we demonstrate a link between PP2A activation and TTP anti-inflammatory function by showing that specific knockdown of TTP with siRNA reversed the repression of TNFα-induced IL-8 and IL-6 mRNA expression and protein secretion by FTY720. Therefore we propose that PP2A activators affect the dynamic equilibrium regulating TTP; shifting the equilibrium from phosphorylated (inactive) towards unphosphorylated (active) but unstable TTP. PP2A activators boost the anti-inflammatory function of TTP and have implications for future pharmacotherapeutic strategies to combat inflammation in respiratory disease

Hereditary sensory neuropathy type 1-associated deoxysphingolipids cause neurotoxicity, acute calcium handling abnormalities and mitochondrial dysfunction in vitro

Hereditary sensory neuropathy type 1 (HSN-1) is a peripheral neuropathy most frequently caused by mutations in the SPTLC1 or SPTLC2 genes, which code for two subunits of the enzyme serine palmitoyltransferase (SPT). SPT catalyzes the first step of de novo sphingolipid synthesis. Mutations in SPT result in a change in enzyme substrate specificity, which causes the production of atypical deoxysphinganine and deoxymethylsphinganine, rather than the normal enzyme product, sphinganine. Levels of these abnormal compounds are elevated in blood of HSN-1 patients and this is thought to cause the peripheral motor and sensory nerve damage that is characteristic of the disease, by a largely unresolved mechanism. In this study, we show that exogenous application of these deoxysphingoid bases causes dose- and time-dependent neurotoxicity in primary mammalian neurons, as determined by analysis of cell survival and neurite length. Acutely, deoxysphingoid base neurotoxicity manifests in abnormal Ca2+ handling by the endoplasmic reticulum (ER) and mitochondria as well as dysregulation of cell membrane store-operated Ca2+ channels. The changes in intracellular Ca2+ handling are accompanied by an early loss of mitochondrial membrane potential in deoxysphingoid base-treated motor and sensory neurons. Thus, these results suggest that exogenous deoxysphingoid base application causes neuronal mitochondrial dysfunction and Ca2+ handling deficits, which may play a critical role in the pathogenesis of HSN-1

Trichloroethylene Exposure during Cardiac Valvuloseptal Morphogenesis Alters Cushion Formation and Cardiac Hemodynamics in the Avian Embryo

It is controversial whether trichloroethylene (TCE) is a cardiac teratogen. We exposed chick embryos to 0, 0.4, 8, or 400 ppb TCE/egg during the period of cardiac valvuloseptal morphogenesis (2–3.3 days’ incubation). Embryo survival, valvuloseptal cellularity, and cardiac hemodynamics were evaluated at times thereafter. TCE at 8 and 400 ppb/egg reduced embryo survival to day 6.25 incubation by 40–50%. At day 4.25, increased proliferation and hypercellularity were observed within the atrioventricular and outflow tract primordia after 8 and 400 ppb TCE. Doppler ultrasound revealed that the dorsal aortic and atrioventricular blood flows were reduced by 23% and 30%, respectively, after exposure to 8 ppb TCE. Equimolar trichloroacetic acid (TCA) was more potent than TCE with respect to increasing mortality and causing valvuloseptal hypercellularity. These results independently confirm that TCE disrupts cardiac development of the chick embryo and identifies valvuloseptal development as a period of sensitivity. The hypercellular valvuloseptal profile is consistent with valvuloseptal heart defects associated with TCE exposure. This is the first report that TCA is a cardioteratogen for the chick and the first report that TCE exposure depresses cardiac function. Valvuloseptal hypercellularity may narrow the cardiac orifices, which reduces blood flow through the heart, thereby compromising cardiac output and contributing to increased mortality. The altered valvuloseptal formation and reduced hemodynamics seen here are consistent with such an outcome. Notably, these effects were observed at a TCE exposure (8 ppb) that is only slightly higher than the U.S. Environmental Protection Agency maximum containment level for drinking water (5 ppb)

The phosphorylated form of FTY720 activates PP2A, represses inflammation and is devoid of S1P agonism in A549 lung epithelial cells

Protein phosphatase 2A (PP2A) activity can be enhanced pharmacologically by PP2A-activating drugs (PADs). The sphingosine analog FTY720 is the best known PAD and we have shown that FTY720 represses production of pro-inflammatory cytokines responsible for respiratory disease pathogenesis. Whether its phosphorylated form, FTY720-P, also enhances PP2A activity independently of the sphingosine 1-phosphate (S1P) pathway was unknown. Herein, we show that FTY720-P enhances TNF-induced PP2A phosphatase activity and significantly represses TNF-induced interleukin 6 (IL-6) and IL-8 mRNA expression and protein secretion from A549 lung epithelial cells. Comparing FTY720 and FTY720-P with S1P, we show that unlike S1P, the sphingosine analogs do not induce cytokine production on their own. In fact, FTY720 and FTY720-P significantly repress S1P-induced IL-6 and IL-8 production. We then examined their impact on expression of cyclooxygenase 2 (COX-2) and resultant prostaglandin E2 (PGE2) production. S1P did not increase production of this pro-inflammatory enzyme because COX-2 mRNA gene expression is NF-κB-dependent, and unlike TNF, S1P did not activate NF-κB. However, TNF-induced COX-2 mRNA expression and PGE2 secretion is repressed by FTY720 and FTY720-P. Hence, FTY720-P enhances PP2A activity and that PADs can repress production of pro-inflammatory cytokines and enzymes in A549 lung epithelial cells in a manner devoid of S1P agonism