The Toll-like receptor 5 ligand flagellin promotes asthma by priming allergic responses to indoor allergens.

Allergic asthma is a complex disease characterized by eosinophilic pulmonary inflammation, mucus production and reversible airway obstruction. Exposure to indoor allergens is a risk factor for asthma, but this disease is also associated with high household levels of total and particularly Gram-negative bacteria. The ability of bacterial products to act as adjuvants suggests they might promote asthma by priming allergic sensitization to inhaled allergens.

Comparison of physician-, biomarker-, and symptom-based strategies for adjustment of inhaled corticosteroid therapy in adults with asthma: the BASALT randomized controlled trial.

Context: No consensus exists for adjusting inhaled corticosteroid therapy in patients with asthma. Approaches include adjustment at outpatient visits guided by physician assessment of asthma control (symptoms, rescue therapy, pulmonary function), based on exhaled nitric oxide, or on a day-to-day basis guided by symptoms.

Objective: To determine if adjustment of inhaled corticosteroid therapy based on exhaled nitric oxide or day-to-day symptoms is superior to guideline-informed, physician assessment-based adjustment in preventing treatment failure in adults with mild to moderate asthma.

An investigation into PEEK-on-PEEK as a bearing surface candidate for cervical total disc replacement.

Background Context: Total disc replacement (TDR) is a relatively new reconstructive non-fusion technology for the spine that aims to overcome some of the limitations of fusion technology. The first generation artificial discs were mainly based on well-known material combinations from total hip replacement.

Purpose: To evaluate the feasibility of PEEK-on-PEEK as a bearing surface material for use in cervical TDR.

IL-13 in asthma and allergic disease: asthma phenotypes and targeted therapies.

Decades of research in animal models have provided abundant evidence to show that IL-13 is a key T(H)2 cytokine that directs many of the important features of airway inflammation and remodeling in patients with allergic asthma. Several promising focused therapies for asthma that target the IL-13/IL-4/signal transducer and activator of transcription 6 pathway are in development, including anti-IL-13 mAbs and IL-4 receptor antagonists. The efficacy of these new potential asthma therapies depends on the responsiveness of patients.

Long-acting β2-agonist step-off in patients with controlled asthma.

Background: Because of concerns about the safety of long-acting β(2)-agonist (LABA) use in patients with asthma, withdrawal of the LABA is recommended by the US Food and Drug Administration once asthma is controlled by combination therapy with a LABA and inhaled corticosteroid (ICS).

Objective: To perform a systematic review and meta-analysis assessing evidence supporting the discontinuation of LABA therapy once asthma control has been achieved with a combination of ICS and LABA.

Data Sources: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched (through August 2010), references of identified studies and selected narrative review articles were evaluated, registries of clinical trials were reviewed, and manufacturers of LABAs were contacted.

The semantics of Chemical Markup Language (CML) for computational chemistry : CompChem.

: This paper introduces a subdomain chemistry format for storing computational chemistry data called CompChem. It has been developed based on the design, concepts and methodologies of Chemical Markup Language (CML) by adding computational chemistry semantics on top of the CML Schema. The format allows a wide range of ab initio quantum chemistry calculations of individual molecules to be stored.

Cationic polythiophene-surfactant self-assembly complexes: phase transitions, optical response, and sensing.

The absorption and photoluminescence spectra of the cationic conjugated polyelectrolyte poly[3-(6-trimethylammoniumhexyl)thiophene] (P3TMAHT) were observed to be dramatically altered in the presence of anionic surfactants due to self-assembly through ionic complex formation. Small-angle neutron scattering (SANS), UV/vis, and photoluminescence spectroscopy were used to probe the relationship between the supramolecular complex organization and the photophysical response of P3TMAHT in the presence of industrially important anionic surfactants. Subtle differences in the surfactant mole fraction and chemical structure (e.

L-Carnitine-supplementation in advanced pancreatic cancer (CARPAN)--a randomized multicentre trial.

Background: Cachexia, a >10% loss of body-weight, is one factor determining the poor prognosis of pancreatic cancer. Deficiency of L-Carnitine has been proposed to cause cancer cachexia.

Findings: We screened 152 and enrolled 72 patients suffering from advanced pancreatic cancer in a prospective, multi-centre, placebo-controlled, randomized and double-blinded trial to receive oral L-Carnitine (4 g) or placebo for 12 weeks.

Do small airway abnormalities characterize asthma phenotypes? In search of proof.

The role of small airway abnormalities in asthma pathogenesis has been extensively studied and debated for several decades. However, whether or not small airway abnormalities play a relevant role in specific phenotypes of asthmatic patients and contribute to clinical presentation is largely unknown. In the present review, we evaluated available data on the role of small airways in severe asthma, with a further focus on asthma in smokers and asthma in the elderly.

Alveolar macrophages from overweight/obese subjects with asthma demonstrate a proinflammatory phenotype.

Rationale: Obesity is associated with increased prevalence and severity of asthma. Adipose tissue macrophages can contribute to the systemic proinflammatory state associated with obesity. However, it remains unknown whether alveolar macrophages have a unique phenotype in overweight/obese patients with asthma.

Studying enzymatic bioreactions in a millisecond microfluidic flow mixer.

In this study, the pre-steady state development of enzymatic bioreactions using a microfluidic mixer is presented. To follow such reactions fast mixing of reagents (enzyme and substrate) is crucial. By using a highly efficient passive micromixer based on multilaminar flow, mixing times in the low millisecond range are reached.

Chronic aspiration shifts the immune response from adaptive immunity to innate immunity in a murine model of asthma.

Objective And Design: The hypothesis that aspiration of gastric fluid drives the anti-ovalbumin response toward a Th2 reaction even in animals not prone to Th2 responses was evaluated.

Subjects: Forty-eight male C57BL/6 mice were used.

Methods: Mice were sensitized and challenged with ovalbumin starting 5 weeks prior to the initiation of weekly aspirations of either gastric fluid or normal saline as a control.

Bronchodilators in heart failure patients with COPD: is it time for a clinical trial?

Chronic heart failure (HF) and chronic obstructive pulmonary disease (COPD) commonly coexist, and patients with both diseases fare worse than those with either disease alone. Several factors may contribute to worse outcomes, including an increased burden of care related to greater disease complexity, an overlap of symptoms resulting in misapplication of therapy, and the adverse effects of treatment for one disease on the symptoms and outcomes related to the other. For example, there are conflicting data about the cardiovascular risks of bronchodilators in HF patients who may experience worse outcomes with inhaled beta-2 agonists via arrhythmogenesis, ischemia, and/or attenuation of beta-blocker benefits.

Identifying differentiation stage of individual primary hematopoietic cells from mouse bone marrow by multivariate analysis of TOF-secondary ion mass spectrometry data.

The ability to self-renew and differentiate into multiple types of blood and immune cells renders hematopoietic stem and progenitor cells (HSPCs) valuable for clinical treatment of hematopoietic pathologies and as models of stem cell differentiation for tissue engineering applications. To study directed hematopoietic stem cell (HSC) differentiation and identify the conditions that recreate the native bone marrow environment, combinatorial biomaterials that exhibit lateral variations in chemical and mechanical properties are employed. New experimental approaches are needed to facilitate correlating cell differentiation stage with location in the culture system.

Mast cell TNF receptors regulate responses to Mycoplasma pneumoniae in surfactant protein A (SP-A)-/- mice.

Background: Mycoplasma pneumoniae (Mp) frequently colonizes the airways of patients with chronic asthma and likely contributes to asthma exacerbations. We previously reported that mice lacking surfactant protein A (SP-A) have increased airway hyperresponsiveness (AHR) during M pneumoniae infection versus wild-type mice mediated by TNF-α. Mast cells (MCs) have been implicated in AHR in asthma models and produce and respond to TNF-α.

Development of a telemedical monitoring concept for the care of malnourished geriatric home-dwelling patients: a pilot study.

Elderly patients are at high risk of malnutrition and sarcopenia, promoting further morbidity which in turn decreases quality of life and increases the claiming of medical services and associated costs. Early and sustained administration of oral nutritional supplements has been shown to improve the nutritional status with robust clinical benefit. Many patients however, poorly adhere to prescribed supplements, so consistent monitoring is needed.

Asthma outcomes: pulmonary physiology.

Background: Outcomes of pulmonary physiology have a central place in asthma clinical research.

Objective: At the request of National Institutes of Health (NIH) institutes and other federal agencies, an expert group was convened to provide recommendations on the use of pulmonary function measures as asthma outcomes that should be assessed in a standardized fashion in future asthma clinical trials and studies to allow for cross-study comparisons.

Methods: Our subcommittee conducted a comprehensive search of PubMed to identify studies that focused on the validation of various airway response tests used in asthma clinical research.

SHP-1 as a critical regulator of Mycoplasma pneumoniae-induced inflammation in human asthmatic airway epithelial cells.

Asthma is a chronic inflammatory disease in which airway epithelial cells are the first line of defense against exposure of the airway to infectious agents. Src homology protein (SHP)-1, a protein tyrosine phosphatase, is a negative regulator of signaling pathways that are critical to the development of asthma and host defense. We hypothesize that SHP-1 function is defective in asthma, contributing to the increased inflammatory response induced by Mycoplasma pneumoniae, a pathogen known to exacerbate asthma.

A quantitative study of the clustering of polycyclic aromatic hydrocarbons at high temperatures.

The clustering of polycyclic aromatic hydrocarbon (PAH) molecules is investigated in the context of soot particle inception and growth using an isotropic potential developed from the benchmark PAHAP potential. This potential is used to estimate equilibrium constants of dimerisation for five representative PAH molecules based on a statistical mechanics model. Molecular dynamics simulations are also performed to study the clustering of homomolecular systems at a range of temperatures.

Clinical value of endosonography in the assessment of laryngeal cancer.

Background: Endosonography has been successfully used in staging gastrointestinal cancer, but its value is as yet undetermined in laryngology.

Methods: This prospective study includes 84 patients undergoing microlaryngoscopy for laryngeal cancer. The results of endosonography were compared with those of CT and MRI in the 76 surgical cases.

Fluorinated colloidal gold immunolabels for imaging select proteins in parallel with lipids using high-resolution secondary ion mass spectrometry.

The local abundance of specific lipid species near a membrane protein is hypothesized to influence the protein's activity. The ability to simultaneously image the distributions of specific protein and lipid species in the cell membrane would facilitate testing these hypotheses. Recent advances in imaging the distribution of cell membrane lipids with mass spectrometry have created the desire for membrane protein probes that can be simultaneously imaged with isotope labeled lipids.