Heterogeneity of severe asthma in childhood: confirmation by cluster analysis of children in the National Institutes of Health/National Heart, Lung, and Blood Institute Severe Asthma Research Program.

Background: Asthma in children is a heterogeneous disorder with many phenotypes. Although unsupervised cluster analysis is a useful tool for identifying phenotypes, it has not been applied to school-age children with persistent asthma across a wide range of severities.

Objectives: This study determined how children with severe asthma are distributed across a cluster analysis and how well these clusters conform to current definitions of asthma severity.

Predictors of substance abuse treatment need and receipt among homeless women.

Many homeless women do not receive needed treatment for substance abuse. This study identified social network and other predisposing factors associated with perceived need for and receipt of substance abuse treatment among 273 homeless women who screened positive for past-year substance abuse. Perceived treatment need was more likely among women with drug-using sex partners, a denser network, and an arrest history but less likely for those with a minor child and a longer history of homelessness.

Vaccination of patients with mild and severe asthma with a 2009 pandemic H1N1 influenza virus vaccine.

Background: Asthma was the most common comorbidity of patients hospitalized with 2009 H1N1 influenza.

Objective: We sought to assess the immunogenicity and safety of an unadjuvanted, inactivated 2009 H1N1 vaccine in patients with severe versus mild-to-moderate asthma.

Methods: We conducted an open-label study involving 390 participants (age, 12-79 years) enrolled in October-November 2009.

Dopamine Release and Uptake Impairments and Behavioral Alterations Observed in Mice that Model Fragile X Mental Retardation Syndrome.

In this study we evaluated the relationship between amphetamine-induced behavioral alterations and dopamine release and uptake characteristics in Fmr1 knockout (Fmr1 KO) mice, which model fragile X syndrome. The behavioral analyses, obtained at millisecond temporal resolution and 2 mm spatial resolution using a force-plate actometer, revealed that Fmr1 KO mice express a lower degree of focused stereotypy compared to wild type (WT) control mice after injection with 10 mg/kg (ip) amphetamine. To identify potentially related neurochemical mechanisms underlying this phenomenon, we measured electrically-evoked dopamine release and uptake using fast-scan cyclic voltammetry at carbon-fiber microelectrodes in striatal brain slices.

Sampling to reduce respondent burden in personal network studies and its effect on estimates of structural measures.

Recently, researchers have been increasingly interested in collecting personal network data. Collecting this type of data is particularly burdensome on the respondents, who need to elicit the names of alters, answer questions about each alter (network composition), and evaluate the strength of possible relationships among the named alters (network structure). In line with McCarty et al.

Use of the Asthma Control Questionnaire to predict future risk of asthma exacerbation.

Background: Direct correlation of assessments of a validated composite measure such as the Asthma Control Questionnaire (ACQ) and risk of exacerbation has not been previously demonstrated in a randomized controlled trial.

Objective: To evaluate the ability of the ACQ score over time to predict risk of a future asthma exacerbation.

Methods: This analysis included data from a 12-week placebo-controlled trial (N = 292) of AMG 317, an IL-4 receptor α antagonist, in patients with moderate to severe atopic asthma.

Racial differences in biologic predictors of severe asthma: Data from the Severe Asthma Research Program.

Background: Biologic factors are known to contribute to asthma severity. It is unknown whether these factors differentially contribute to asthma severity in black compared with white subjects.

Objective: We sought to assess the extent to which racial disparities between black and white subjects with severe asthma are attributable to physiologic, immunoinflammatory, and sociodemographic variables.

Determinants of exhaled breath condensate pH in a large population with asthma.

Background: Exhaled breath condensate (EBC) pH is 2 log orders below normal during acute asthma exacerbations and returns to normal with antiinflammatory therapy. However, the determinants of EBC pH, particularly in stable asthma, are poorly understood. We hypothesized that patients with severe asthma would have low EBC pH and that there would be an asthma subpopulation of patients with characteristically low values.

Uniform definition of asthma severity, control, and exacerbations: document presented for the World Health Organization Consultation on Severe Asthma.

Asthma is a global health problem affecting around 300 million individuals of all ages, ethnic groups and countries. It is estimated that around 250,000 people die prematurely each year as a result of asthma. Concepts of asthma severity and control are important in evaluating patients and their response to treatment, as well as for public health, registries, and research (clinical trials, epidemiologic, genetic, and mechanistic studies), but the terminology applied is not standardized, and terms are often used interchangeably.

Controlling cardiomyocyte length: the role of renin and PPAR-{gamma}.

Aims: Renin and peroxisome proliferator-activated receptor (PPAR-γ) interact directly with cardiomyocytes and influence protein synthesis. We investigated their effects and interaction on the size of cardiomyocytes.

Methods And Results: Effects of renin and PPAR-γ activation were studied in cultured adult rat ventricular cardiomyocytes, transgenic mice with a cardiomyocyte-restricted knockout of PPAR-γ, and transgenic rats overexpressing renin, TGR(mRen2)27.

Re-examining the directional-ordering transition in the compass model with screw-periodic boundary conditions.

We study the directional-ordering transition in the two-dimensional classical and quantum compass models on the square lattice by means of Monte Carlo simulations. An improved algorithm is presented which builds on the Wolff cluster algorithm in one-dimensional subspaces of the configuration space. This improvement allows us to study classical systems up to L=512.

Permanent make-up colorants may cause severe skin reactions.

Background: In recent years, cosmetic tattoos [permanent make-up (PMU)] on eyelids, eyebrows and lips have become increasingly popular. However, most colorants are manufactured for non-medical purposes, without any established history of safe use in humans.

Objectives: To investigate severe adverse reactions, such as swelling, burning, and the development of papules, of the lips and the surrounding area in 4 patients who had had at least two PMU procedures on their lips.

Mast cell phenotype, location, and activation in severe asthma. Data from the Severe Asthma Research Program.

Rationale: Severe asthma (SA) remains poorly understood. Mast cells (MC) are implicated in asthma pathogenesis, but it remains unknown how their phenotype, location, and activation relate to asthma severity.

Objectives: To compare MC-related markers measured in bronchoscopically obtained samples with clinically relevant parameters between normal subjects and subjects with asthma to clarify their pathobiologic importance.

Predicting intermediate phenotypes in asthma using bronchoalveolar lavage-derived cytokines.

An important problem in realizing personalized medicine is the development of methods for identifying disease subtypes using quantitative proteomics. Recently we found that bronchoalveolar lavage (BAL) cytokine patterns contain information about dynamic lung responsiveness. In this study, we examined physiological data from 1,048 subjects enrolled in the US Severe Asthma Research Program (SARP) to identify four largely separable, quantitative intermediate phenotypes.

TLR4/MyD88-induced CD11b+Gr-1 int F4/80+ non-migratory myeloid cells suppress Th2 effector function in the lung.

In humans, environmental exposure to a high dose of lipopolysaccharide (LPS) protects from allergic asthma, the immunological underpinnings of which are not well understood. In mice, exposure to a high LPS dose blunted house dust mite-induced airway eosinophilia and T-helper 2 (Th2) cytokine production. Although adoptively transferred Th2 cells induced allergic airway inflammation in control mice, they were unable to do so in LPS-exposed mice.

Personal network correlates of alcohol, cigarette, and marijuana use among homeless youth.

Background: Youth who are homeless and on their own are among the most marginalized individuals in the United States and face multiple risks, including use of substances. This study investigates how the use of alcohol, cigarettes, and marijuana among homeless youth may be influenced by characteristics of their social networks.

Methods: Homeless youth aged 13-24 were randomly sampled from 41 service and street sites in Los Angeles County (N=419).

TGF-beta1 improves cardiac performance via up-regulation of laminin receptor 37/67 in adult ventricular cardiomyocytes.

TGF-beta1 plays an important role in cardiac fibrosis, apoptosis, induction of hypertrophy and contractile dysfunction. This study investigates whether TGF-beta1 plays a role in laminin receptor 37/67 (37/67 LR)-dependent regulation of cardiac performance. Therefore, isolated adult cardiomyocytes were stimulated with TGF-beta1, the expression of the 37/67 LR was determined and cell shortening was investigated on cells attached to a non-specific, serum-based attachment substrate or to specific, laminin-coated dishes.

Pulmonary function abnormalities in HIV-infected patients during the current antiretroviral therapy era.

Rationale: Before the introduction of combination antiretroviral (ARV) therapy, patients infected with HIV had an increased prevalence of respiratory symptoms and lung function abnormalities. The prevalence and exact phenotype of pulmonary abnormalities in the current era are unknown. In addition, these abnormalities may be underdiagnosed.

When, where, why and with whom homeless women engage in risky sexual behaviors: A framework for understanding complex and varied decision-making processes.

Impoverished women worldwide are at high risk for contracting HIV/AIDS. This study explores how homeless women make risky sex decisions and the role that alcohol and drugs play in this process. We analyze 56 in-depth qualitative descriptions of recent sexual episodes among 28 women living in shelters in Los Angeles, California, USA.

Asthma phenotypes in adults and clinical implications.

It is becoming increasingly recognized that asthma is a heterogeneous disease, whether based on clinical factors, including the patient's age at diagnosis, symptom spectrum and treatment response, triggering factors, or the level and type of inflammation. Attempts to analyze the importance of these characteristics to the clinical presentation of asthma have led to the appreciation of numerous separate and overlapping asthma phenotypes. However, these approaches are 'biased' and based on the clinician/scientist's own experience.

Enhanced suppressive function of regulatory T cells from patients with immune-mediated diseases following successful ex vivo expansion.

Recent studies and our current data demonstrated the deficits in the numbers and/or functions of the CD4(+)CD25(+)Foxp3(+) Treg cells in the patients with autoimmune diseases, indicating that restoration of Treg cells in these patients could be a potential therapeutic approach. Here, we demonstrated that CD4(+)CD25(+)Foxp3(+) Treg cells can be purified, activated and expanded from peripheral blood of patients with immune-mediated diseases, to a similar degree to those from healthy donors. Within 3weeks, Treg cells from most patients could be expanded ex vivo 100-2000 fold and maintained their phenotypic characteristics.

New insights into paracrine mechanisms of human cardiac progenitor cells.

Aims: Cardiac progenitor cells (CPCs) have been shown to promote cardiac regeneration in vivo. Understanding the function of CPCs is essential for further implementation of these cells in the treatment of cardiac diseases. The present study tested the hypothesis that adult CPC exert paracrine effects that lead to an improvement in the functional characteristics of cardiomyocytes.

Surface sensitivity in scanning transmission x-ray microspectroscopy using secondary electron detection.

The successful integration of electron detection into an existing scanning transmission x-ray microspectroscope (STXM) at the Swiss Light Source is demonstrated. In conventional x-ray detection using a photomultiplier, STXM offers mainly bulk sensitivity combined with high lateral resolution. However, by implementation of a channeltron electron multiplier, the surface sensitivity can be established by the detection of secondary electrons emitted from the sample upon resonant excitation.

Current concepts in laser tattoo removal.

Today, more than 10% of the Western population has at least 1 tattoo, with prevalence of up to one-fourth in the cohort younger than 30 years of age. Many of these individuals come to regret their decision within months due to several reasons, often socially-related, and seek medical treatment. The discovery of selective photothermolysis has enabled the targeted destruction of tattoo pigments with only minimal damage to the surrounding tissue and limited risk of adverse effects, which contrasts previously used nonspecific methods.