Asthma Phenotypes in Childhood

INTRODUCTION: Asthma is no longer thought of as a single disease, but rather a collection of varying symptoms expressing different disease patterns. One of the ongoing challenges is understanding the underlying pathophysiological mechanisms that may be responsible for the varying responses to treatment. Areas Covered: This review provides an overview of our current understanding of the asthma phenotype concept in childhood and describes key findings from both conventional and data-driven methods. Expert Commentary: With the vast amounts of data generated from cohorts, there is hope that we can elucidate distinct pathophysiological mechanisms, or endotypes. In return, this would lead to better patient stratification and disease management, thereby providing true personalised medicine

Immunohistochemical analysis of oxidative stress and DNA repair proteins in normal mammary and breast cancer tissues

<p>Abstract</p> <p>Background</p> <p>During the course of normal cellular metabolism, oxygen is consumed and reactive oxygen species (ROS) are produced. If not effectively dissipated, ROS can accumulate and damage resident proteins, lipids, and DNA. Enzymes involved in redox regulation and DNA repair dissipate ROS and repair the resulting damage in order to preserve a functional cellular environment. Because increased ROS accumulation and/or unrepaired DNA damage can lead to initiation and progression of cancer and we had identified a number of oxidative stress and DNA repair proteins that influence estrogen responsiveness of MCF-7 breast cancer cells, it seemed possible that these proteins might be differentially expressed in normal mammary tissue, benign hyperplasia (BH), ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC).</p> <p>Methods</p> <p>Immunohistochemistry was used to examine the expression of a number of oxidative stress proteins, DNA repair proteins, and damage markers in 60 human mammary tissues which were classified as BH, DCIS or IBC. The relative mean intensity was determined for each tissue section and ANOVA was used to detect statistical differences in the relative expression of BH, DCIS and IBC compared to normal mammary tissue.</p> <p>Results</p> <p>We found that a number of these proteins were overexpressed and that the cellular localization was altered in human breast cancer tissue.</p> <p>Conclusions</p> <p>Our studies suggest that oxidative stress and DNA repair proteins not only protect normal cells from the damaging effects of ROS, but may also promote survival of mammary tumor cells.</p

Broad Antibody Mediated Cross-Neutralization and Preclinical Immunogenicity of New Codon-Optimized HIV-1 Clade CRF02_AG and G Primary Isolates

Creation of an effective vaccine for HIV has been an elusive goal of the scientific community for almost 30 years. Neutralizing antibodies are assumed to be pivotal to the success of a prophylactic vaccine but previous attempts to make an immunogen capable of generating neutralizing antibodies to primary “street strain” isolates have resulted in responses of very limited breadth and potency. The objective of the study was to determine the breadth and strength of neutralizing antibodies against autologous and heterologous primary isolates in a cohort of HIV-1 infected Nigerians and to characterize envelopes from subjects with particularly broad or strong immune responses for possible use as vaccine candidates in regions predominated by HIV-1 CRF02_AG and G subtypes. Envelope vectors from a panel of primary Nigerian isolates were constructed and tested with plasma/sera from the same cohort using the PhenoSense HIV neutralizing antibody assay (Monogram Biosciences Inc, USA) to assess the breadth and potency of neutralizing antibodies. The immediate goal of this study was realized by the recognition of three broadly cross-neutralizing sera: (NG2-clade CRF02_AG, NG3-clade CRF02_AG and NG9- clade G). Based on these findings, envelope gp140 sequences from NG2 and NG9, complemented with a gag sequence (Clade G) and consensus tat (CRF02_AG and G) antigens have been codon-optimized, synthesized, cloned and evaluated in BALB/c mice. The intramuscular administration of these plasmid DNA constructs, followed by two booster DNA immunizations, induced substantial specific humoral response against all constructs and strong cellular responses against the gag and tat constructs. These preclinical findings provide a framework for the design of candidate vaccine for use in regions where the HIV-1 epidemic is driven by clades CRF02_AG and G

Biomechanical analysis and modeling of different vertebral growth patterns in adolescent idiopathic scoliosis and healthy subjects

<p>Abstract</p> <p>Background</p> <p>The etiology of AIS remains unclear, thus various hypotheses concerning its pathomechanism have been proposed. To date, biomechanical modeling has not been used to thoroughly study the influence of the abnormal growth profile (i.e., the growth rate of the vertebral body during the growth period) on the pathomechanism of curve progression in AIS. This study investigated the hypothesis that AIS progression is associated with the abnormal growth profiles of the anterior column of the spine.</p> <p>Methods</p> <p>A finite element model of the spinal column including growth dynamics was utilized. The initial geometric models were constructed from the bi-planar radiographs of a normal subject. Based on this model, five other geometric models were generated to emulate different coronal and sagittal curves. The detailed modeling integrated vertebral body growth plates and growth modulation spinal biomechanics. Ten years of spinal growth was simulated using AIS and normal growth profiles. Sequential measures of spinal alignments were compared.</p> <p>Results</p> <p>(1) Given the initial lateral deformity, the AIS growth profile induced a significant Cobb angle increase, which was roughly between three to five times larger compared to measures utilizing a normal growth profile. (2) Lateral deformities were absent in the models containing no initial coronal curvature. (3) The presence of a smaller kyphosis did not produce an increase lateral deformity on its own. (4) Significant reduction of the kyphosis was found in simulation results of AIS but not when using the growth profile of normal subjects.</p> <p>Conclusion</p> <p>Results from this analysis suggest that accelerated growth profiles may encourage supplementary scoliotic progression and, thus, may pose as a progressive risk factor.</p

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Recycling Attitudes and Behavior among a Clinic-Based Sample of Low-Income Hispanic Women in Southeast Texas

We examined attitudes and behavior surrounding voluntary recycling in a population of low-income Hispanic women. Participants (N = 1,512) 18–55 years of age completed a self-report survey and responded to questions regarding household recycling behavior, recycling knowledge, recycling beliefs, potential barriers to recycling (transportation mode, time), acculturation, demographic characteristics (age, income, employment, marital status, education, number of children, birth country), and social desirability. Forty-six percent of participants (n = 810) indicated that they or someone else in their household recycled. In a logistic regression model controlling for social desirability, recycling behavior was related to increased age (P<0.05), lower acculturation (P<0.01), knowing what to recycle (P<0.01), knowing that recycling saves landfill space (P<0.05), and disagreeing that recycling takes too much time (P<0.001). A Sobel test revealed that acculturation mediated the relationship between recycling knowledge and recycling behavior (P<0.05). We offer new information on recycling behavior among Hispanic women and highlight the need for educational outreach and intervention strategies to increase recycling behavior within this understudied population

Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV

The Protease Inhibitor Alpha-2-Macroglobuline-Like-1 Is the p170 Antigen Recognized by Paraneoplastic Pemphigus Autoantibodies in Human

Paraneoplastic pemphigus (PNP) is a devastating autoimmune blistering disease, involving mucocutaneous and internal organs, and associated with underlying neoplasms. PNP is characterized by the production of autoantibodies targeting proteins of the plakin and cadherin families involved in maintenance of cell architecture and tissue cohesion. Nevertheless, the identity of an antigen of Mr 170,000 (p170), thought to be critical in PNP pathogenesis, has remained unknown