Staphylococcal enterotoxin sensitization in a community-based population : a potential role in adult-onset asthma

Background: Recent studies suggest that Staphylococcus aureus enterotoxin sensitization is a risk factor for asthma. However, there is a paucity of epidemiologic evidence on adult-onset asthma in community-based populations. Objective: We sought to evaluate the epidemiology and the clinical significance of staphylococcal enterotoxin sensitization in community-based adult populations. Methods: The present analyses were performed using the baseline data set of Korean adult population surveys, consisting of 1080 adults (mean age=60.2years) recruited from an urban and a rural community. Questionnaires, methacholine challenge tests, and allergen skin tests were performed for defining clinical phenotypes. Sera were analysed for total IgE and enterotoxin-specific IgE using ImmunoCAP. Results: Staphylococcal enterotoxin sensitization (0.35kU/L) had a prevalence of 27.0%. Risk factors were identified as male sex, current smoking, advanced age (61years), and inhalant allergen sensitization. Current asthma was mostly adult onset (18years old) and showed independent associations with high enterotoxin-specific IgE levels in multivariate logistic regression tests. In multivariate linear regressions, staphylococcal enterotoxin-specific IgE level was identified as the major determinant factor for total IgE level. Conclusions and Clinical Relevance: Staphylococcal enterotoxin sensitization was independently associated with adult-onset asthma in adult community populations. Strong correlations between the enterotoxin-specific IgE and total IgE levels support the clinical significance. The present findings warrant further studies for the precise roles of staphylococcal enterotoxin sensitization in the asthma pathogenesis

Surgical Navigation System for Transsphenoidal Pituitary Surgery Applying U-Net-Based Automatic Segmentation and Bendable Devices

Conventional navigation systems used in transsphenoidal pituitary surgery have limitations that may lead to organ damage, including long image registration time, absence of alarms when approaching vital organs and lack of 3-D model information. To resolve the problems of conventional navigation systems, this study proposes a U-Net-based, automatic segmentation algorithm for optical nerves and internal carotid arteries, by training patient computed tomography angiography images. The authors have also developed a bendable endoscope and surgical tool to eliminate blind regions that occur when using straight, rigid, conventional endoscopes and surgical tools during transsphenoidal pituitary surgery. In this study, the effectiveness of a U-Net-based navigation system integrated with bendable surgical tools and a bendable endoscope has been demonstrated through phantom-based experiments. In order to measure the U-net performance, the Jaccard similarity, recall and precision were calculated. In addition, the fiducial and target registration errors of the navigation system and the accuracy of the alarm warning functions were measured in the phantom-based environment. © 2019 by the authors.1

Evaluation of the pathogenicity of GJB3 and GJB6 variants associated with nonsyndromic hearing loss

AbstractA number of genes responsible for hearing loss are related to ion recycling and homeostasis in the inner ear. Connexins (Cx26 encoded by GJB2, Cx31 encoded by GJB3 and Cx30 encoded by GJB6) are core components of gap junctions in the inner ear. Gap junctions are intercellular communication channels and important factors that are associated with hearing loss. To date, a molecular genetics study of GJB3 and GJB6 as a causative gene for hearing loss has not been performed in Korea. This study was therefore performed to elucidate the genetic characteristics of Korean patients with nonsyndromic sensorineural hearing loss and to determine the pathological mechanism of hearing loss by analyzing the intercellular communication function of Cx30 and Cx31 variants. Sequencing analysis of the GJB3 and GJB6 genes in our population revealed a total of nine variants, including four novel variants in the two genes. Three of the novel variants (Cx31-p.V27M, Cx31-p.V43M and Cx-30-p.I248V) and two previously reported variants (Cx31-p.V84I and Cx30-p.A40V) were selected for functional studies using a pathogenicity prediction program and assessed for whether the mutations were located in a conserved region of the protein. The results of biochemical and ionic coupling tests showed that both the Cx31-p.V27M and Cx31-p.V84I variants did not function normally when each was expressed as a heterozygote with the wild-type Cx31. This study demonstrated that two variants of Cx31 were pathogenic mutations with deleterious effect. This information will be valuable in understanding the pathogenic role of GJB3 and GJB6 mutations associated with hearing loss

Improving Detection Accuracy of Lung Cancer Serum Proteomic Profiling via Two-Stage Training Process

<p>Abstract</p> <p>Background</p> <p>Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS) is a frequently used technique for cancer biomarker research. The specificity of biomarkers detected by SELDI can be influenced by concomitant inflammation. This study aimed to increase detection accuracy using a two-stage analysis process.</p> <p>Methods</p> <p>Sera from 118 lung cancer patients, 72 healthy individuals, and 31 patients with inflammatory disease were randomly divided into training and testing groups by 3:2 ratio. In the training group, the traditional method of using SELDI profile analysis to directly distinguish lung cancer patients from sera was used. The two-stage analysis of distinguishing the healthy people and non-healthy patients (1^st-stage) and then differentiating cancer patients from inflammatory disease patients (2^nd-stage) to minimize the influence of inflammation was validated in the test group.</p> <p>Results</p> <p>In the test group, the one-stage method had 87.2% sensitivity, 37.5% specificity, and 64.4% accuracy. The two-stage method had lower sensitivity (> 70.1%) but statistically higher specificity (80%) and accuracy (74.7%). The predominantly expressed protein peak at 11480 Da was the primary splitter regardless of one- or two-stage analysis. This peak was suspected to be SAA (Serum Amyloid A) due to the similar m/z countered around this area. This hypothesis was further tested using an SAA ELISA assay.</p> <p>Conclusions</p> <p>Inflammatory disease can severely interfere with the detection accuracy of SELDI profiles for lung cancer. Using a two-stage training process will improve the specificity and accuracy of detecting lung cancer.</p

A functional promoter polymorphism in monocyte chemoattractant protein–1 is associated with increased susceptibility to pulmonary tuberculosis

We examined the distribution of single nucleotide polymorphisms (SNPs) in nitric oxide synthase 2A, monocyte chemoattractant protein–1 (MCP-1), regulated on activation, normal T cell expressed and secreted, and macrophage inflammatory protein–1α genes in tuberculosis patients and healthy controls from Mexico. The odds of developing tuberculosis were 2.3- and 5.4-fold higher in carriers of MCP-1 genotypes AG and GG than in homozygous AA. Cases of homozygous GG had the highest plasma levels of MCP-1 and the lowest plasma levels of IL-12p40, and these values were negatively correlated. Furthermore, stimulation of monocytes from healthy carriers of the genotype GG with Mycobacterium tuberculosis antigens yielded higher MCP-1 and lower IL-12p40 concentrations than parallel experiments with monocytes from homozygous AA. Addition of anti–MCP-1 increased IL-12p40 levels in cultures of M. tuberculosis–stimulated monocytes from homozygous GG, and addition of exogenous MCP-1 reduced IL-12p40 production by M. tuberculosis–stimulated monocytes from homozygous AA. Furthermore, we could replicate our results in Korean subjects, in whom the odds of developing tuberculosis were 2.8- and 6.9-fold higher in carriers of MCP-1 genotypes AG and GG than in homozygous AA. Our findings suggest that persons bearing the MCP-1 genotype GG produce high concentrations of MCP-1, which inhibits production of IL-12p40 in response to M. tuberculosis and increases the likelihood that M. tuberculosis infection will progress to active pulmonary tuberculosis

Polarity-tunable magnetic tunnel junctions based on ferromagnetism at oxide heterointerfaces

Complex oxide systems have attracted considerable attention because of their fascinating properties, including the magnetic ordering at the conducting interface between two band insulators, such as LaAlO3 (LAO) and SrTiO3 (STO). However, the manipulation of the spin degree of freedom at the LAO/STO heterointerface has remained elusive. Here, we have fabricated hybrid magnetic tunnel junctions consisting of Co and LAO/STO ferromagnets with the insertion of a Ti layer in between, which clearly exhibit magnetic switching and the tunnelling magnetoresistance (TMR) effect below 10 K. The magnitude and the of the TMR are strongly dependent on the direction of the rotational magnetic field parallel to the LAO/STO plane, which is attributed to a strong Rashba-type spin orbit coupling in the LAO/STO heterostructure. Our study provides a further support for the existence of the macroscopic ferromagnetism at LAO/STO heterointerfaces and opens a novel route to realize interfacial spintronics devices.Comment: 25 pages, 5 figure