Training Programs for Improving Speech Perception in Noise: A Review.

Understanding speech in the presence of noise is difficult and challenging, even for people with normal hearing. Accurate pitch perception, coding and decoding of temporal and intensity cues, and cognitive factors are involved in speech perception in noise (SPIN); disruption in any of these can be a barrier to SPIN. Because the physiological representations of sounds can be corrected by exercises, training methods for any impairment can be used to improve speech perception.

Insights into the present and future of cartilage regeneration and joint repair.

Knee osteoarthritis is the most common joint disease. It causes pain and suffering for affected patients and is the source of major economic costs for healthcare systems. Despite ongoing research, there is a lack of knowledge regarding disease mechanisms, biomarkers, and possible cures.

Differentiation of induced pluripotent stem cells into definitive endoderm on Activin A-functionalized gradient surfaces.

Activin A plays a central role in the differentiation of stem cells into definitive endoderm, the first step in embryonic development and function development in many organ systems. The aims of this study were to induce controlled and fine-tuned cell differentiation using a gradient nanotechnology and compare this with a classic protocol and to investigate how induced pluripotent stem cells differentiated depending on the gradual increase of Activin A. The density difference was tested by attaching Activin A to a gold nanoparticle gradient for high-precision density continuity.

Metabolic effects of Lactobacillus reuteri DSM 17938 in people with type 2 diabetes: A randomized controlled trial.

Aims: To investigate the metabolic effects of 12-week oral supplementation with Lactobacillus reuteri DSM 17938 in patients with type 2 diabetes on insulin therapy.

Materials And Methods: In a double-blind trial, we randomized 46 people with type 2 diabetes to placebo or a low (10  CFU/d) or high dose (10  CFU/d) of L. reuteri DSM 17938 for 12 weeks.

ARAP2 promotes GLUT1-mediated basal glucose uptake through regulation of sphingolipid metabolism.

Lipid droplet formation, which is driven by triglyceride synthesis, requires several droplet-associated proteins. We identified ARAP2 (an ADP-ribosylation factor 6 GTPase-activating protein) in the lipid droplet proteome of NIH-3T3 cells and showed that knockdown of ARAP2 resulted in decreased lipid droplet formation and triglyceride synthesis. We also showed that ARAP2 knockdown did not affect fatty acid uptake but reduced basal glucose uptake, total levels of the glucose transporter GLUT1, and GLUT1 levels in the plasma membrane and the lipid micro-domain fraction (a specialized plasma membrane domain enriched in sphingolipids).

Increased expression of IRF4 and ETS1 in CD4+ cells from patients with intermittent allergic rhinitis.

Background:   The transcription factor (TF) IRF4 is involved in the regulation of Th1, Th2, Th9, and Th17 cells, and animal studies have indicated an important role in allergy. However, IRF4 and its target genes have not been examined in human allergy.

Methods:   IRF4 and its target genes were examined in allergen-challenged CD4(+) cells from patients with IAR, using combined gene expression microarrays and chromatin immunoprecipitation chips (ChIP-chips), computational target prediction, and RNAi knockdowns.

The formation of lipid droplets: possible role in the development of insulin resistance/type 2 diabetes.

Neutral lipids are stored in so-called lipid droplets, which are formed as small primordial droplets at microsomal membranes and increase in size by a fusion process. The fusion is catalyzed by the SNARE proteins SNAP23, syntaxin-5 and VAMP4. SNAP23 is involved in the insulin dependent translocation of GLUT4 to the plasma membrane, and has an important role in the development of insulin resistance.

A pathway-based approach to find novel markers of local glucocorticoid treatment in intermittent allergic rhinitis.

Background: Glucocorticoids (GCs) may affect the expression of hundreds of genes in different cells and tissues from patients with intermittent allergic rhinitis (IAR). It is a formidable challenge to understand these complex changes by studying individual genes. In this study, we aimed to identify (i) pathways affected by local GC treatment and (ii) examine if those pathways could be used to find novel markers of local GC treatment in nasal fluids from patients with IAR.

Allergen challenge of peripheral blood mononuclear cells from patients with seasonal allergic rhinitis increases IL-17RB, which regulates basophil apoptosis and degranulation.

Background: Previously, expression profiling has been used to analyse allergen-challenged T-helper type 2 cells, nasal biopsies and nasal fluid cells from patients with seasonal allergic rhinitis (SAR). Allergen-challenged peripheral blood mononuclear cells (PBMCs) provide a human in vitro model of how antigen-presenting cells, CD4+ T cells and effector cells such as basophils interact in allergic inflammation.

Objective: To identify novel genes and pathways in allergen-challenged PBMCs from patients with SAR using gene expression profiling and functional studies.

Network properties of complex human disease genes identified through genome-wide association studies.

Background: Previous studies of network properties of human disease genes have mainly focused on monogenic diseases or cancers and have suffered from discovery bias. Here we investigated the network properties of complex disease genes identified by genome-wide association studies (GWAs), thereby eliminating discovery bias.

Principal Findings: We derived a network of complex diseases (n = 54) and complex disease genes (n = 349) to explore the shared genetic architecture of complex diseases.

A haplotype in the inducible T-cell tyrosine kinase is a risk factor for seasonal allergic rhinitis.

Background: Identification of disease-associated single nucleotide polymorphisms (SNPs) in seasonal allergic rhinitis (SAR) may be facilitated by focusing on genes in a disease-associated pathway.

Objective: To search for SNPs in genes that belong to the T-cell receptor (TCR) pathway and that change in expression in allergen-challenged CD4+ cells from patients with SAR.

Methods: CD4+ cells from patients with SAR were analysed with gene expression microarrays.

A module-based analytical strategy to identify novel disease-associated genes shows an inhibitory role for interleukin 7 Receptor in allergic inflammation.

Background: The identification of novel genes by high-throughput studies of complex diseases is complicated by the large number of potential genes. However, since disease-associated genes tend to interact, one solution is to arrange them in modules based on co-expression data and known gene interactions. The hypothesis of this study was that such a module could be a) found and validated in allergic disease and b) used to find and validate one ore more novel disease-associated genes.

Gender differences in inflammatory proteins and pathways in seasonal allergic rhinitis.

In model organisms, thousands of genes differ in expression between females and males. It is not known if differences on a similar scale are found in humans nor how this relates to disease. However, in allergic disease gender differences in the levels of both inflammatory cells and proteins have been shown.

The effects of hypoxia and hypercapnia on renal and heart function, haemodynamics and plasma hormone levels in stable COPD patients.

Background: Fluid retention with oedema is an important clinical problem in advanced chronic obstructive pulmonary disease (COPD).

Objective: The aim of this study was to investigate cardiovascular, hormonal, renal and pulmonary function data and their possible relation to fluid retention in COPD.

Methods: The study group consisted of 25 stable outpatients with COPD.

IgGs and Mabs against the beta2-adrenoreceptor block A-V conduction in mouse hearts: A possible role in the pathogenesis of ventricular arrhythmias.

Autoantibodies against beta-adrenoceptors might be involved in different cardiomyopathic diseases such as idopathic dilated cardiomyopathy, Chagas' disease and ventricular arrhythmias. To study the effects of such antibodies on the whole heart, we made use of a new technique allowing the measurement of Ca++ transients as well as action potentials in Langendorff preparations of mouse hearts. Mouse antibodies directed against the second extracellular loop of the beta2-adrenoceptor induced conduction blocks which could be washed away by the beta2-adrenoceptor inverse agonist ICI118,551, confirming the specificity and non-toxicity of these events.

Hyperinsulinemia: effect on cardiac mass/function, angiotensin II receptor expression, and insulin signaling pathways.

To investigate the association between hyperinsulinemia and cardiac hypertrophy, we treated rats with insulin for 7 wk and assessed effects on myocardial growth, vascularization, and fibrosis in relation to the expression of angiotensin II receptors (AT-R). We also characterized insulin signaling pathways believed to promote myocyte growth and interact with proliferative responses mediated by G protein-coupled receptors, and we assessed myocardial insulin receptor substrate-1 (IRS-1) and p110 alpha catalytic and p85 regulatory subunits of phospatidylinositol 3 kinase (PI3K), Akt, MEK, ERK1/2, and S6 kinase-1 (S6K1). Left ventricular (LV) geometry and performance were evaluated echocardiographically.

Influence of central inhibition of sympathetic nervous activity on myocardial metabolism in chronic heart failure: acute effects of the imidazoline I1-receptor agonist moxonidine.

Although beta-adrenergic blockade is beneficial in heart failure, inhibition of central sympathetic outflow using moxonidine has been associated with increased mortality. In the present study, we studied the acute effects of the imidazoline-receptor agonist moxonidine on haemodynamics, NA (noradrenaline) kinetics and myocardial metabolism. Fifteen patients with CHF (chronic heart failure) were randomized to a single dose of 0.

Ser49Gly of beta1-adrenergic receptor is associated with effective beta-blocker dose in dilated cardiomyopathy.

Objective: Our objective was to evaluate the influence of polymorphisms at codons 49 and 389 of the beta1-adrenergic receptor (beta1-AR) on the response to beta-blockers and outcome in patients with dilated cardiomyopathy.

Methods: We genotyped both codons of the beta1-AR in 375 patients with dilated cardiomyopathy and 492 control subjects.

Results: Neither of the polymorphisms was associated with susceptibility for dilated cardiomyopathy.

The therapeutic potential of immune therapy in idiopathic dilated cardiomyopathy.

Idiopathic dilated cardiomyopathy (DCM) is a heart muscle disease of unknown origin and the second most common reason for heart transplantation. Genetic factors, viral persistence and the presence of an autoimmune response against myocardial epitopes are believed to play a major pathogenic role in idiopathic DCM. Pathogenic circulating autoantibodies against several cardiac proteins have been detected in sera from idiopathic DCM patients.

Selective cerebral overexpression of growth hormone alters cardiac function, morphology, energy metabolism and catecholamines in transgenic mice.

Background: Growth hormone (GH) has important regulatory effects on cardiac morphology and function both during normal development as well as in pathophysiological settings such as myocardial infarction (MI) and congestive heart failure (CHF). In order to investigate in more detail the interaction between GH and sympathetic nervous system (SNS) system we studied the effects of selective cerebral GH overexpression on myocardial content of catecholamines, myocardial and brain energy metabolism as well as on cardiac function during resting and stress conditions in a transgenic mouse model.

Methods: Transgenic mice with selective bovine GH overexpression under control of glial fibrillary acidic protein promoter in the brain (GFAP-bGH, n=15) were created and compared to genetically matched non-transgenic mates (Control, n=15).

Beneficial effect on cardiac function by intravenous immunoglobulin treatment in patients with dilated cardiomyopathy is not due to neutralization of anti-receptor autoantibody.

Anti-beta1-adrenoceptor (beta1AR) autoantibodies have been shown to be pathophysiologically important in idiopathic dilated cardiomyopathy (DCM). Treatment with intravenous immunoglobulin (IVIG) has shown beneficial effects in both DCM and ischemic cardiomyopathy. However, the underlying mechanism has not been clarified.

Reduced sympathetic responsiveness as well as plasma and tissue noradrenaline concentration in growth hormone transgenic mice.

Aims: Acromegaly [overproduction of growth hormone (GH)] and GH deficiency have both been associated with alterations in autonomic nervous system function. The aim of this study was to investigate autonomic nervous system influence on heart rate (HR) in transgenic mice overexpressing bovine GH (bGH).

Methods: HR and HR variability (HRV) were measured in conscious young (8-13 weeks) and old (5-6 months) female bGH and control mice using telemetry.