Eye Closure Interacts with Music to Influence Vividness and Content of Directed Imagery

Goal-directed, intentional mental imagery generation supports a range of daily self-regulatory activities, such as planning, decision-making, and recreational escapism. Many clinical interventions for mood and anxiety disorders also use imagery and their effectiveness can be affected by an individual's ability to manipulate vividness and content of mental imagery. Prior literature points towards music as a promising candidate to influence imagination in such settings, but basic questions remain regarding how music affects mental imagery and how it interacts with basic, well-established parameters, such as facilitatory effects of eye closure. One hundred participants listened to music and a silent control whilst performing a guided mental imagery task. Specifically, participants saw a short video of a figure journeying towards a landmark and imagined a continuation of the journey with either closed or open eyes. After each trial, participants reported vividness and content of their imagined journeys. Bayesian Mixed Effects Models obtained strong evidence of greater vividness, duration, as well as distance travelled in music conditions compared to silent conditions. Additionally, interactive effects of music and eye closure were found for both vividness and the emotional valence of imagined content, where music effects were disproportionately amplified by eye closure. Findings further support music's potential to manipulate the perceptual, spatial-temporal, as well as emotional sentiment of deliberately generated mental imagery

The relation between plasma tyrosine concentration and fatigue in primary biliary cirrhosis and primary sclerosing cholangitis

BACKGROUND: In primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) fatigue is a major clinical problem. Abnormal amino acid (AA) patterns have been implicated in the development of fatigue in several non-hepatological conditions but for PBC and PSC no data are available. This study aimed to identify abnormalities in AA patterns and to define their relation with fatigue. METHODS: Plasma concentrations of tyrosine, tryptophan, phenylalanine, valine, leucine and isoleucine were determined in plasma of patients with PBC (n = 45), PSC (n = 27), chronic hepatitis C (n = 22) and healthy controls (n = 73). Fatigue and quality of life were quantified using the Fisk fatigue severity scale, a visual analogue scale and the SF-36. RESULTS: Valine, isoleucine, leucine were significantly decreased in PBC and PSC. Tyrosine and phenylalanine were increased (p < 0.0002) and tryptophan decreased (p < 0.0001) in PBC. In PBC, but not in PSC, a significant inverse relation between tyrosine concentrations and fatigue and quality of life was found. Patients without fatigue and with good quality of life had increased tyrosine concentrations compared to fatigued patients. Multivariate analysis indicated that this relation was independent from disease activity or severity or presence of cirrhosis. CONCLUSION: In patients with PBC and PSC, marked abnormalities in plasma AA patterns occur. Normal tyrosine concentrations, compared to increased concentrations, may be associated with fatigue and diminished quality of life

Regulation of neutrophil senescence by microRNAs

Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF. This is then followed by their subsequent removal by phagocytic cells such as macrophages, thereby preventing unwanted inflammation and tissue damage. Neutrophils translate mRNA to make new proteins that are important in maintaining functional longevity. We therefore hypothesised that neutrophil functions and lifespan might be regulated by microRNAs expressed within human neutrophils. Total RNA from highly purified neutrophils was prepared and subjected to microarray analysis using the Agilent human miRNA microarray V3. We found human neutrophils expressed a selected repertoire of 148 microRNAs and that 6 of these were significantly upregulated after a period of 4 hours in culture, at a time when the contribution of apoptosis is negligible. A list of predicted targets for these 6 microRNAs was generated from http://mirecords.biolead.org and compared to mRNA species downregulated over time, revealing 83 genes targeted by at least 2 out of the 6 regulated microRNAs. Pathway analysis of genes containing binding sites for these microRNAs identified the following pathways: chemokine and cytokine signalling, Ras pathway, and regulation of the actin cytoskeleton. Our data suggest that microRNAs may play a role in the regulation of neutrophil senescence and further suggest that manipulation of microRNAs might represent an area of future therapeutic interest for the treatment of inflammatory disease

Insulin resistance in type 1 diabetes: what is ‘double diabetes’ and what are the risks?

In this review, we explore the concept of ‘double diabetes’, a combination of type 1 diabetes with features of insulin resistance and type 2 diabetes. After considering whether double diabetes is a useful concept, we discuss potential mechanisms of increased insulin resistance in type 1 diabetes before examining the extent to which double diabetes might increase the risk of cardiovascular disease (CVD). We then go on to consider the proposal that weight gain from intensive insulin regimens may be associated with increased CV risk factors in some patients with type 1 diabetes, and explore the complex relationships between weight gain, insulin resistance, glycaemic control and CV outcome. Important comparisons and contrasts between type 1 diabetes and type 2 diabetes are highlighted in terms of hepatic fat, fat partitioning and lipid profile, and how these may differ between type 1 diabetic patients with and without double diabetes. In so doing, we hope this work will stimulate much-needed research in this area and an improvement in clinical practice

Zinc sulfate as an adjunct to methylphenidate for the treatment of attention deficit hyperactivity disorder in children: A double blind and randomized trial [ISRCTN64132371]

BACKGROUND: Attention-deficit hyperactivity disorder is an early-onset, clinically heterogenous disorder of inattention, hyperactivity, and impulsiveness. The diagnosis and treatment of attention-deficit hyperactivity disorder continues to raise controversy, and, there is also an increase in treatment options. In this 6-week double blind, placebo controlled-trial, we assessed the effects of zinc plus methylphenidate in the treatment of children with attention deficit hyperactivity disorder. To the best of our knowledge, this study is the first double blind and placebo controlled clinical trial assessing the adjunctive role of zinc in ADHD. METHODS: Our subjects were 44 outpatient children (26 boys and 18 girls) between the ages of 5–11 (mean ± SD was 7.88 ± 1.67) who clearly met the DSM IV diagnostic criteria for attention-deficit hyperactivity disorder and they were randomized to methylphenidate 1 mg/kg/day + zinc sulfate 55 mg/day (with approximately 15 mg zinc element) (group 1) and methylphenidate 1 mg/kg/day + placebo (sucrose 55 mg) (group 2) for a 6 week double blind clinical trial. The principal measure of the outcome was the Teacher and Parent ADHD Rating Scale. Patients were assessed by a child psychiatrist at baseline, 14, 28 and 42 days after the medication started. RESULTS: The present study shows the Parent and Teacher Rating Scale scores improved with zinc sulfate over this 6-week, double blind and placebo controlled trial. The behavior of the two treatments was not homogeneous across the time. The difference between the two protocols was significant as indicated by the effect on the group, the between-subjects factor (F = 4.15, d.f. = 1, P = 0.04; F = 4.50, d.f. = 1, P = 0.04 respectively). The difference between the two groups in the frequency of side effects was not significant. CONCLUSIONS: This double-blind, placebo-controlled study demonstrated that zinc as a supplementary medication might be beneficial in the treatment of children with attention-deficit hyperactivity disorder. However, further investigations and different doses of zinc are required to replicate these findings in children with ADHD

Antihyperlipidemic and antiperoxidative effect of Diasulin, a polyherbal formulation in alloxan induced hyperglycemic rats

BACKGROUND: This study was undertaken to investigation the effect of Diasulin, a poly herbal drug composed of ethanolic extract of ten medicinal plants on blood glucose, plasma insulin, tissue lipid profile, and lipidperoxidation in alloxan induced diabetes. METHODS: Ethanolic extract of Diasulin a, poly herbal drug was administered orally (200 mg/kg body weight) for 30 days. The different doses of Diasulin on blood glucose and plasma insulin in diabetic rats were studied and the levels of lipid peroxides [TBARS, and Hydroperoxide] and tissue lipids [cholesterol, triglyceride, phospholipides and free fatty acids] were also estimated in alloxan induced diabetic rats. The effects were compared with glibenclamide. RESULT: Treatment with Diasulin and glibenclamide resulted in a significant reduction of blood glucose and increase in plasma insulin. Diasulin also resulted in a significant decrease in tissue lipids and lipid peroxide formation. The effect produced by Diasulin was comparable with that of glibenclamide. CONCLUSION: The decreased lipid peroxides and tissue lipids clearly showed the antihyperlipidemic and antiperoxidative effect of Diasulin apart from its antidiabetic effect

Effects of an attention demanding task on dynamic stability during treadmill walking

<p>Abstract</p> <p>Background</p> <p>People exhibit increased difficulty balancing when they perform secondary attention-distracting tasks while walking. However, a previous study by Grabiner and Troy (<it>J. Neuroengineering Rehabil</it>., 2005) found that young healthy subjects performing a concurrent Stroop task while walking on a motorized treadmill exhibited <it>decreased </it>step width variability. However, measures of variability do not directly quantify how a system responds to perturbations. This study re-analyzed data from Grabiner and Troy 2005 to determine if performing the concurrent Stroop task directly affected the dynamic stability of walking in these same subjects.</p> <p>Methods</p> <p>Thirteen healthy volunteers walked on a motorized treadmill at their self-selected constant speed for 10 minutes both while performing the Stroop test and during undisturbed walking. This Stroop test consisted of projecting images of the name of one color, printed in text of a different color, onto a wall and asking subjects to verbally identify the color of the text. Three-dimensional motions of a marker attached to the base of the neck (C5/T1) were recorded. Marker velocities were calculated over 3 equal intervals of 200 sec each in each direction. Mean variability was calculated for each time series as the average standard deviation across all strides. Both "local" and "orbital" dynamic stability were quantified for each time series using previously established methods. These measures directly quantify how quickly small perturbations grow or decay, either continuously in real time (local) or discretely from one cycle to the next (orbital). Differences between Stroop and Control trials were evaluated using a 2-factor repeated measures ANOVA.</p> <p>Results</p> <p>Mean variability of trunk movements was significantly reduced during the Stroop tests compared to normal walking. Conversely, local and orbital stability results were mixed: some measures showed slight increases, while others showed slight decreases. In many cases, different subjects responded differently to the Stroop test. While some of our comparisons reached statistical significance, many did not. In general, measures of variability and dynamic stability reflected different properties of walking dynamics, consistent with previous findings.</p> <p>Conclusion</p> <p>These findings demonstrate that the decreased movement variability associated with the Stroop task did <it>not </it>translate to greater dynamic stability.</p

Pharmacokinetics of Two Common Antiretroviral Regimens in Older HIV-Infected Patients: A Pilot Study

The pharmacokinetics (PK) of antiretrovirals (ARVs) in older HIV-infected patients are poorly described. Here, the steady-state PK of 2 common ARV regimens (tenofovir [TFV]/emtricitabine [FTC]/efavirenz [EFV]; TFV/FTC/atazanavir [ATV]/ritonavir [RTV]) in older non-frail HIV-infected patients are presented

HSP90 inhibitors disrupt a transient HSP90-HSF1 interaction and identify a noncanonical model of HSP90-mediated HSF1 regulation

Heat shock factor 1 (HSF1) initiates a broad transcriptional response to proteotoxic stress while also mediating a cancer-specific transcriptional program. HSF1 is thought to be regulated by molecular chaperones, including Heat Shock Protein 90 (HSP90). HSP90 is proposed to sequester HSF1 in unstressed cells, but visualization of this interaction in vivo requires protein crosslinking. In this report, we show that HSP90 binding to HSF1 depends on HSP90 conformation and is only readily visualized for the ATP-dependent, N-domain dimerized chaperone, a conformation only rarely sampled by mammalian HSP90. We have used this mutationally fixed conformation to map HSP90 binding sites on HSF1. Further, we show that ATP-competitive, N-domain targeted HSP90 inhibitors disrupt this interaction, resulting in the increased duration of HSF1 occupancy of the hsp70 promoter and significant prolongation of both the constitutive and heat-induced HSF1 transcriptional activity. While our data do not support a role for HSP90 in sequestering HSF1 monomers to suppress HSF1 transcriptional activity, our findings do identify a noncanonical role for HSP90 in providing dynamic modulation of HSF1 activity by participating in removal of HSF1 trimers from heat shock elements in DNA, thus terminating the heat shock response

Academic and social integration and study progress in problem based learning

The present study explores the effects of problem-based learning (PBL) on social and academic integration and study progress. Three hundred and five first-year students from three different psychology curricula completed a questionnaire on social and academic integration. Effects of a full-fledged PBL environment were compared to (1) effects of a conventional lecture-based learning environment, and (2) effects of a learning environment that combined lectures and other methods aimed at activating students. Lisrel analyses show direct positive effects of the learning environment on study progress: students in PBL obtained more credits compared to students in more conventional curricula. Moreover, the levels of social and academic integration were also higher among students in the PBL curriculum. The links between integration and study progress were less straightforward. Formal social integration positively affected study progress, but informal academic integration was negatively related to study progress