Stroke : hope through research /

Mode of access: Internet.

Stroke : research highlights /

Mode of access: Internet.

The mouse sulfate anion transporter gene Sat1 (Slc26a1): Cloning, tissue distribution, gene structure, functional characterization, and transcriptional regulation by thyroid hormone

Sulfate (SO42-) is required for bone/cartilage formation and cellular metabolism. sat-1 is a SO42- anion transporter expressed on basolateral membranes of renal proximal tubules, and is suggested to play an important role in maintaining SO42- homeostasis. As a first step towards studying its tissue-specific expression, hormonal regulation, and in preparation for the generation of knockout mice, we have cloned and characterized the mouse sat-1 cDNA (msat-1), gene (sat1; Slc26a1) and promoter region. msat-1 encodes a 704 amino acid protein (75.4 kDa) with 12 putative transmembrane domains that induce SO42- (also oxalate and chloride) transport in Xenopus oocytes. msat-1 mRNA was expressed in kidney, liver, cecum, calvaria, brain, heart, and skeletal muscle. Two distinct transcripts were expressed in kidney and liver due to alternative utilization of the first intron, corresponding to an internal portion of the 5'-untranslated region. The Sa1 gene (similar to6 kb) consists of 4 exons. Its promoter is similar to52% G+C rich and contains a number of well-characterized cis-acting elements, including sequences resembling hormone responsive elements T3REs and VDREs. We demonstrate that Sat1 promoter driven basal transcription in OK cells was stimulated by tri-iodothyronine. Site-directed mutagenesis identified an imperfect T3RE at -454-bp in the Sat1 promoter to be responsible for this activity. This study represents the first characterization of the structure and regulation of the Sat1 gene encoding a SO42-/chloride/oxalate anion transporter.

Are diagnosis specific outcome indicators based on administrative data useful in assessing quality of hospital care?

Background: Hospital performance reports based on administrative data should distinguish differences in quality of care between hospitals from case mix related variation and random error effects. A study was undertaken to determine which of 12 diagnosis-outcome indicators measured across all hospitals in one state had significant risk adjusted systematic ( or special cause) variation (SV) suggesting differences in quality of care. For those that did, we determined whether SV persists within hospital peer groups, whether indicator results correlate at the individual hospital level, and how many adverse outcomes would be avoided if all hospitals achieved indicator values equal to the best performing 20% of hospitals. Methods: All patients admitted during a 12 month period to 180 acute care hospitals in Queensland, Australia with heart failure (n = 5745), acute myocardial infarction ( AMI) ( n = 3427), or stroke ( n = 2955) were entered into the study. Outcomes comprised in-hospital deaths, long hospital stays, and 30 day readmissions. Regression models produced standardised, risk adjusted diagnosis specific outcome event ratios for each hospital. Systematic and random variation in ratio distributions for each indicator were then apportioned using hierarchical statistical models. Results: Only five of 12 (42%) diagnosis-outcome indicators showed significant SV across all hospitals ( long stays and same diagnosis readmissions for heart failure; in-hospital deaths and same diagnosis readmissions for AMI; and in-hospital deaths for stroke). Significant SV was only seen for two indicators within hospital peer groups ( same diagnosis readmissions for heart failure in tertiary hospitals and inhospital mortality for AMI in community hospitals). Only two pairs of indicators showed significant correlation. If all hospitals emulated the best performers, at least 20% of AMI and stroke deaths, heart failure long stays, and heart failure and AMI readmissions could be avoided. Conclusions: Diagnosis-outcome indicators based on administrative data require validation as markers of significant risk adjusted SV. Validated indicators allow quantification of realisable outcome benefits if all hospitals achieved best performer levels. The overall level of quality of care within single institutions cannot be inferred from the results of one or a few indicators.

Experience as a moderator of involvement and satisfaction on brand loyalty in a business-to-business setting 02-314R

This paper examines the relative influence of two key antecedents of brand loyalty-satisfaction and involvement and the moderating role of experience, using a sample of business buyers. The central argument of this paper is that the strength of the effect of these variables on attitudinal brand loyalty will vary with the level of customer experience with purchasing the service. Building on previous research which examined low-risk, customer product settings [Kim, J., Lim, J.S., & Bhargava, M. (1998). The role of affect in attitude formation: A classical conditioning approach. Journal of the Academy of Marketing Science 26 (2): pp. 143-152; Shiv, B., & Fedorikhin, A. (1999). Heart and mind in conflict: The interplay of affect and cognition in consumer decision-making. Journal of Consumer Research 26: 278], this study shows that for a high-risk setting, involvement with the service category will be more dominant in its influence on brand loyalty than satisfaction with the preferred brand. Furthermore, it was found that experience moderated the influence of involvement and satisfaction on attitudinal brand loyalty for a high-risk business-to-business service. This study provides new insights into the theory and practice of buyer behavior and business-to-business brands. Crown Copyright (C) 2004 Published by Elsevier Inc. All rights reserved.

Impact of premorbid undernutrition on outcome in stroke patients

Background and Purpose - To assess the prevalence of premorbid undernutrition and its impact on outcomes 1 month after stroke. Methods - The study recruited from consecutive stroke admissions during a 10-month period. Premorbid nutritional status ( using the subjective global assessment [SGA]), premorbid functioning ( modified Rankin scale [MRS]), and stroke severity ( National Institutes of Health Stroke Scale [NIHSS] score) were assessed at admission. The associations between premorbid nutritional status, poor outcome ( defined as MRS greater than or equal to 3), and mortality were examined before and after adjustment for confounding variables, including age, gender, stroke risk factors, stroke severity, and admission serum albumin. Results - Thirty of 185 patients were assessed as having undernutrition at admission. Significant unadjusted associations were observed between undernutrition and poor outcome (odds ratio [OR], 3.4; 95% CI, 1.3 to 8.7; P = 0.01), and mortality (OR, 3.1, 95% CI, 1.3 to 7.7; P = 0.02) at 1 month. NIHSS, age, and premorbid MRS were also significantly associated with poor outcomes. After adjustment for these factors, the effect size of associations remained important but not significant ( poor outcome: OR, 2.4; 95% CI, 0.7 to 9.0, P = 0.18; mortality: OR, 3.2; 95% CI, 1.0 to 10.4, P = 0.05). Conclusions - Premorbid undernutrition, as assessed using the SGA, appears to be an independent predictor of poor stroke outcome. Stroke prevention strategies should target undernutrition in the population at risk for stroke to improve outcomes.

Sequence, circulating levels, and expression of C-type natriuretic peptide in a euryhaline elasmobranch, Carcharhinus leucas

The present study has examined expression and circulating levels of C-type natriuretic peptide (CNP) in the euryhaline bull shark, Carcharhinus leucas. Complementary DNA and deduced amino acid sequence for CNP in C leucas were determined by RACE methods. Homology of CNP amino acid sequence in C. leucas was high both for proCNP and for mature CNP when compared with previously identified elasmobranch CNPs. Mature CNP sequence in C. leucas was identical to that in Triakis seyllia and Seyliorhinus canicula. Levels of expression of CNP mRNA were significantly decreased in the atrium but did not change in either the brain or ventricle following acclimation to a SW environment. However, circulating levels of CNP significantly increased from 86.0 +/- 7.9 fmol ml(-1) in FW to 144.9 +/- 19.5 fmol ml(-1) in SW. The results presented demonstrate that changes in environmental salinity influences both synthesis of CNP from the heart and also circulating levels in C. leucas. Potential stimulus for release and modes of action are discussed. (c) 2005 Elsevier Inc. All rights reserved.

Carvedilol blocks beta(2)- more than beta(1)-adrenoceptors in human heart

Objective: To understand the basis of the effectiveness of carvedilol in heart failure by determining its specific properties at human heart and beta(2)-adrenoceptors. Methods: The positive inotropic effects of noradrenaline (in the presence of the beta(2)-selective antagonist ICI118551) and adrenaline (in the presence of the beta(1)-selective antagonist CGP20712), mediated through beta(1)- and beta(2)-adrenoceptors, respectively, were investigated in atrial and ventricular trabeculae. The patch-clamp technique was used to investigate effects of noradrenaline and adrenaline on L-type Ca2+ current in human atrial myocytes. Results: Carvedilol was a 13-fold more potent competitive antagonist of the effects of adrenaline at 1 2-adrenoceptors (-logK(B) = 10.13 +/- 0.08) than of noradrenaline at beta(1)-adrenoceptors (-logK(B) = 9.02 +/- 0.07) in human right atrium. Chronic carvedilol treatment of patients with non-terminal heart failure reduced the inotropic sensitivity of atrial trabeculae to noradrenaline and adrenaline 5.6-fold and 91.2-fold, respectively, compared to beta(1)-blocker-treated patients, consistent with persistent preferential blockade of beta(2)-adrenoceptors. In terminal heart failure carvedilol treatment reduced 1.8-fold and 25.1-fold the sensitivity of right ventricular trabeculae to noradrenaline and adrenaline, respectively, but metoprolol treatment did not reduce the sensitivity to the catecholamines. Increases of current (I-Ca,I-L) produced by noradrenaline and adrenaline were not different in atrial myocytes obtained from non-terminal heart failure patients treated with metoprolol or carvedilol, consistent with dissociation of both beta-blockers from the receptors. Conclusions: Carvedilol blocks human cardiac beta(2)-adrenoceptors more than beta(1)-adrenoceptors, thereby conceivably contributing to the beneficial effects in heart failure. The persistent blockade of beta-adrenoceptors is attributed to accumulation of carvedilol in cardiac tissue. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

Circadian blood pressure variation after acute stroke

We aimed to characterise the patterns of circadian blood pressure (BP) variation after acute stroke and determine whether any relationship exists between these patterns and stroke outcome. BP was recorded manually every 4 h for 48 h following acute stroke. Patients were classified according to the percentage fall in mean systolic BP (SBP) at night compared to during the day as: dippers (fall >= 10-= 20%); non-dippers (>= 0-

Increased health care utilization and increased antiretroviral use in HIV-infected individuals with mental health disorders

Objectives The aims of the study were to describe the prevalence and associations of mental health disorder (MHD) among a cohort of HIV-infected patients attending the Victorian HIV/AIDS Service between 1984 and 2000, and to examine whether antiretroviral therapy use or mortality was influenced by MHD (defined as a record of service provision by psychiatric services on the Victorian Psychiatric Case Register). It was hypothesized that HIV-positive individuals with MHD would have poorer treatment outcomes, reduced responses to highly active antiretroviral therapy (HAART) and increased mortality compared with those without MHD. Methods This is a retrospective cohort of 2981 individuals (73% of the Victorian population diagnosed with HIV infection) captured on an HIV database which was electronically matched with the public Victorian Psychiatric Case Register (VPCR) (accounting for 95% of public system psychiatry service provision). The prevalence, dates and recorded specifics of mental health disorders at the time of the electronic match on 1 June 2000 are described. The association with recorded MHD, gender, age, AIDS illness, HIV exposure category, duration and type of antiviral therapy, treatment era (prior to 1986, post-1987 and pre-HAART, and post-HAART) on hospitalization and mortality at 1 September 2001 was assessed. Results Five hundred and twenty-five individuals (17.6% of the Victorian HIV-positive population) were recorded with MHD, most frequently coded as attributable to substance dependence/abuse or affective disorder. MHD was diagnosed prior to HIV in 33% and, of those diagnosed after HIV, 93.8% were recorded more than 1 year after the HIV diagnosis. Schizophrenia was recorded in 6% of the population with MHD. Hospitalizations for both psychiatric and nonpsychiatric illness were more frequent in those with MHD (relative risk 5.4; 95% confidence interval 3.7, 8.2). The total number of antiretrovirals used (median 6.4 agents vs 5.5 agents) was greater in those with MHD. When adjusted for antiretroviral treatment era, HIV exposure category, CD4 cell count and antiretroviral therapy, survival was not affected by MHD. Conclusions MHD is frequent in this population with HIV infection and is associated with increased healthcare utilization but not with reduced survival.

Binding and hydrodynamic properties of muscarinic receptor subtypes solubilized in 3-(3-cholamidopropyl)dimethylammonio-2-hydroxy-1-propanesulfonate

The muscarinic receptor from the cerebral cortex, heart, and lacrimal gland can be solubilized in the zwitterionic detergent 3-(3-cholamidopropyl)dimethylammonio-2-hydroxy-1-propane sulfonate (CHAPSO) with retention of high affinity [3H]N-methyls-copolamine binding. However, in this detergent there are significant differences in the binding properties of the receptors, compared with those observed in membranes and digitonin solution. Some agents retain a degree of selectivity. In the heart and cortex, agonists can bind with high affinity to a receptor-GTP-binding protein complex. A second, lower affinity, agonist binding state is also present, which resembles a class of sites seen in membranes but not in digitonin solution. The high affinity agonist binding state has been resolved from the lower affinity state on sucrose density gradient centrifugation. Hydrodynamic analysis suggests that the high affinity state is approximately 110,000 Da larger than the lower affinity state. The binding properties of the receptor in CHAPSO can be altered to those seen in digitonin by exchanging detergents after CHAPSO solubilization.

Paternal low protein diet affects adult offspring cardiovascular and metabolic function in mice

Although the association between maternal periconceptional diet and adult offspring health is well characterised, our understanding of the impact of paternal nutrition at the time of conception on offspring phenotype remains poorly defined. Therefore, we determined the effect of a paternal preconception low protein diet (LPD on adult offspring cardiovascular and metabolic health in mice. Male C57BL/6 mice were fed either normal protein diet (NPD; 18% casein or LPD (9% casein for 7 wk before mating. At birth, a reduced male-to-female ratio (P = 0.03 and increased male offspring weight (P = 0.009 were observed in litters from LPD compared with NPD stud males with no differences in mean litter size. LPD offspring were heavier than NPD offspring at 2 and 3 wk of age (P <0.02. However, no subsequent differences in body weight were observed. Adult male offspring derived from LPD studs developed relative hypotension (decreased by 9.2 mmHg and elevated heart rate (P <0.05, whereas both male and female offspring displayed vascular dysfunction and impaired glucose tolerance relative to NPD offspring. At cull (24 wk, LPD males had elevated adiposity (P = 0.04, reduced heart-to-body weight ratio (P = 0.04, and elevated circulating TNF-α levels (P = 0.015 compared with NPD males. Transcript expression in offspring heart and liver tissue was reduced for genes involved in calcium signaling (Adcy, Plcb, Prkcb and metabolism (Fto in LPD offspring (P <0.03. These novel data reveal the impact of suboptimal paternal nutrition on adult offspring cardiovascular and metabolic homeostasis, and provide some insight into the underlying regulatory mechanisms.

Illness perceptions predict reassurance following a negative exercise stress testing result

Many patients are not reassured after receiving normal results following cardiac investigations. While previous studies have shown anxiety to be a contributing factor, little research has investigated the influence of patients’ illness perceptions on reassurance. In this study we investigated whether illness perceptions predicted patients’ reassurance following normal exercise stress test results. Sixty-two chest pain patients without prior diagnosed cardiac pathology completed questionnaires assessing anxiety and illness perceptions prior to exercise stress testing. Patients completed a reassurance questionnaire immediately following their appointment and again one month later. Illness perceptions (consequences, timeline, identity, illness concern, and emotional effect) but not anxiety, significantly predicted reassurance immediately following testing. We found both state anxiety and illness perceptions to predict reassurance one month later. After controlling for anxiety, longer timeline and lower treatment control beliefs predicted lower reassurance. The results suggest that an intervention targeting patients who have high anxiety and negative illness perceptions prior to testing may improve reassurance and decrease disability and the subsequent use of medical care.

The ‘first three years’ movement and the infant brain:a review of critiques

This article reviews a particular aspect of the critique of the increasing focus on the brain and neuroscience; what has been termed by some, 'neuromania'. It engages with the growing literature produced in response to the 'first three years' movement: an alliance of child welfare advocates and politicians that draws on the authority of neuroscience to argue that social problems such as inequality, poverty, educational underachievement, violence and mental illness are best addressed through 'early intervention' programmes to protect or enhance emotional and cognitive aspects of children's brain development. The movement began in the United States in the early 1990s and has become increasingly vocal and influential since then, achieving international legitimacy in the United States, Canada, New Zealand, Australia, the UK and elsewhere. The movement, and the brain-based culture of expert-led parent training that has grown with it, has been criticised for claiming scientific authority whilst taking a cavalier approach to scientific method and evidence; for being overly deterministic about the early years of life; for focusing attention on individual parental failings rather than societal or structural problems, for adding to the expanding anxieties of parents and strengthening the intensification of parenting and, ultimately, for redefining the parent-child relationship in biologised, instrumental and dehumanised terms. © 2014 John Wiley & Sons Ltd.