Publication date: 2018
Source:Principles and Practice of Pediatric Infectious Diseases
Author(s): Raymond A. Strikas, Alison C. Mawle, Larry K. Pickering, Walter A. Orenstein
http://ift.tt/2vsVijj
Παρασκευή 21 Ιουλίου 2017
6 Active Immunization
Estimating environmental value losses from earth materials excavation and infilling for large-scale airport construction: a case of Dalian Offshore Airport, Dalian, China
Abstract
Large-scale airport construction removes large quantities of earth materials, resulting in serious environmental pollution and ecosystem damage. However, studies of environmental concerns caused by the materials used in airport construction are still preliminary, and those case studies on the impacts of large-scale offshore airport development are very limited. China's Dalian Offshore Airport is considered here to study the environmental value loss from 240 million m3 of materials excavations and 21 km2 of artificial island infillings. The findings show that the calculated annual environmental value loss for the development of the Dalian Offshore Airport is approximately US$7.75 million, including US$1.81 million and US$1.47 million of direct economic loss of timber resources and marine biology resources, respectively, and US$1.53 million and US$2.79 million value losses of forest and marine ecosystem services damaged caused by materials excavation and infilling, respectively. The conclusions of this study provide an important foundation to quantitatively analyse the environmental impact of the Dalian Offshore Airport's development and can be used as a reference for similar engineering and environment impact assessment programs.
http://ift.tt/2txieR7
Peroxisome proliferator-activated receptor gamma expression in peripheral blood mononuclear cells and angiopoietin-like protein 4 levels in obese children and adolescents
Abstract
Purpose
The peroxisome proliferator-activated receptor γ (PPARγ) is highly expressed in adipose tissue and functions as transcriptional regulator of metabolism and adipocyte differentiation. Angiopoietin-like protein 4 (ANGPTL4), a central player in various aspects of energy homoeostasis, is induced by PPARγ. The aim of this study was to evaluate ANGPTL4 plasma levels and PPARγ gene expression in peripheral blood mononuclear cells (PBMCs) of children and adolescents with obesity and their association with metabolic parameters.
Methods
Seventy children and adolescents (35 obese and 35 age- and gender-matched control subjects), were selected. PBMCs were separated and their total RNA was extracted. After cDNA synthesis, PPARG gene expression was analyzed by real-time PCR. Relative differences in gene expression were calculated by ΔCt method using β-actin as a normalizer. Serum ANGPTL4 and insulin were measured using ELISA, and insulin resistance (IR) was calculated by the homeostatic model assessment of insulin resistance (HOMA-IR). Fasting plasma glucose (FPG), triglyceride, total cholesterol, LDL-C and HDL-C were also measured.
Results
The expression of the PPARG gene as well as the plasma ANGPTL4 levels were significantly diminished in obese subjects as compared to control ones. However, they were not significantly different in obese children with IR compared to obese children without IR or in those with or without metabolic syndrome. A significant positive correlation was found between PPARγ and ANGPTL4 (r = 0.364, p = 0.002). PPARγ expression levels were also significantly correlated with FPG (r = −0.35, p = 0.003).
Conclusion
PPARγ is decreased in childhood obesity and may be responsible for diminished ANGPTL4 levels.
http://ift.tt/2uJ0qBM
Editorial Board
Source:Journal of Autoimmunity, Volume 82
http://ift.tt/2uHNkFw
Development of autoantibodies precedes clinical manifestations of autoimmune diseases: A comprehensive review
Source:Journal of Autoimmunity
Author(s): Wen-Tao Ma, Christopher Chang, M. Eric Gershwin, Zhe-Xiong Lian
The etiology of autoimmune diseases is due to a combination of genetic predisposition and environmental factors that alter the expression of immune regulatory genes through various mechanisms including epigenetics. Both humoral and cellular elements of the adaptive immune system play a role in the pathogenesis of autoimmune diseases and the presence of autoantibodies have been detected in most but not all autoimmune diseases before the appearance of clinical symptoms. In some cases, the presence or levels of these autoantibodies portends not only the risk of developing a corresponding autoimmune disease, but occasionally the severity as well. This observation is intriguing because it suggests that we can, to some degree, predict who may or may not develop autoimmune diseases. However, the role of autoantibodies in the pathogenesis of autoimmune diseases, whether they actually affect disease progression or are merely an epiphenomenon is still not completely clear in many autoimmune diseases. Because of these gaps in our knowledge, the ability to accurately predict a future autoimmune disease can only be considered a relative risk factor. Importantly, it raises the critical question of defining other events that may drive a patient from a preclinical to a clinical phase of disease.
http://ift.tt/2uiLTKR
Motion monitoring during a course of lung radiotherapy with anchored electromagnetic transponders
Abstract
Purpose
Anchored electromagnetic transponders for tumor motion monitoring during lung radiotherapy were clinically evaluated. First, intrafractional motion patterns were analyzed as well as their interfractional variations. Second, intra- and interfractional changes of the geometric transponder positions were investigated.
Materials and methods
Intrafractional motion data from 7 patients with an upper or middle lobe tumor and three implanted transponders each was used to calculate breathing amplitudes, overall motion amount and motion midlines in three mutual perpendicular directions and three-dimensionally (3D) for 162 fractions. For 6 patients intra- and interfractional variations in transponder distances and in the size of the triangle defined by the transponder locations over the treatment course were determined.
Results
Mean 3D values of all fractions were up to 4.0, 4.6 and 3.4 mm per patient for amplitude, overall motion amount and midline deviation, respectively. Intrafractional transponder distances varied with standard deviations up to 3.2 mm, while a maximal triangle shrinkage of 36.5% over 39 days was observed.
Conclusions
Electromagnetic real-time motion monitoring was feasible for all patients. Detected respiratory motion was on average modest in this small cohort without lower lobe tumors, but changes in motion midline were of the same size as the amplitudes and greater midline motion can be observed in some fractions. Intra- and interfractional variations of the geometric transponder positions can be large, so for reliable motion management correlation between transponder and tumor motion needs to be evaluated per patient.
http://ift.tt/2tmSMd1
Isoalantolactone derivative promotes glucose utilization in skeletal muscle cells and increases energy expenditure in db/db mice via activating AMPK-dependent signaling
Source:Molecular and Cellular Endocrinology
Author(s): Deepti Arha, E. Ramakrishna, Anand P. Gupta, Amit K. Rai, Aditya Sharma, Ishbal Ahmad, Mohammed Riyazuddin, Jiaur R. Gayen, Rakesh Maurya, Akhilesh K. Tamrakar
Augmenting glucose utilization and energy expenditure in skeletal muscle via AMP-activated protein kinase (AMPK) is an imperative mechanism for the management of type 2 diabetes. Chemical derivatives (2a-2h, 3, 4a-4d, 5) of the isoalantolactone (K007), a bioactive molecule from roots of Inula racemosa were synthesized to optimize the bioactivity profile to stimulate glucose utilization in skeletal muscle cells. Interestingly, 4a augmented glucose uptake, driven by enhanced translocation of glucose transporter 4 (GLUT4) to cell periphery in L6 rat skeletal muscle cells. The effect of 4a was independent to phosphatidylinositide-3-kinase (PI-3-K)/Akt pathway, but mediated through Liver kinase B1 (LKB1)/AMPK-dependent signaling, leading to activation of downstream targets acetyl coenzyme A carboxylase (ACC) and sterol regulatory element binding protein 1c (SREBP-1c). In db/db mice, 4a administration decreased blood glucose level and improved body mass index, lipid parameters and glucose tolerance associated with elevation of GLUT4 expression in skeletal muscle. Moreover, 4a increased energy expenditure via activating substrate utilization and upregulated the expression of thermogenic transcription factors and mitochondrial proteins in skeletal muscle, suggesting the regulation of energy balance. These findings suggest the potential implication of isoalantolactone derivatives for the management of diabetes.
http://ift.tt/2uHcrrU
Selective ER-α agonist alleviates vascular endothelial dysfunction in ovariectomized type 2 diabetic rats
Source:Molecular and Cellular Endocrinology
Author(s): Seema Bansal, Kanwaljit Chopra
Postmenopausal diabetic women represent a specific risk group with a greater incidence of vascular deficits as compared with age-matched men or non-diabetic women. 17β-estradiol is the mainstay therapy for menopause and associated complications; however, its vasculoprotective effect is lost in women with diabetes. Although, exact mechanism of dichotomous effect of estrogen has not been delineated but it may be due to, differential activation of ER-α and β during disease conditions such as diabetes. Thus main objective of our study was to characterize the specific estrogen receptor which could be selectively targeted to achieve vasculoprotection in postmenopausal diabetic situation. A significant impairment in glycemic and lipid profile, decreased ACh-induced endothelium dependent relaxation, impaired endothelial integrity, and rise in inflammatory and oxidative stress markers were observed in ovariectomized type 2 diabetic rats as compared to sham rats. These markers were further correlated with aortic eNOS levels. Treatment with selective ER-α receptor agonist markedly while 17β-estradiol partially ameliorated these alterations along with enhanced aortic eNOS levels. However, ER-β agonist did not show any effect. Our data suggests that selective ER-α activation could be an important pharmacological target, to mimic the beneficial effect of estradiol in cardiovascular disorders, especially in postmenopausal diabetic state.
http://ift.tt/2ujbiUE
Bisphenol A affects trophoblast invasion by inhibiting CXCL8 expression in decidual stromal cells
Source:Molecular and Cellular Endocrinology
Author(s): Xiaoqian Li, Yina Wang, Pu Wei, Dongyan Shi, Shuang Wen, Fengjiao Wu, Lixin Liu, Ninghe Ye, Hong Zhou
Bisphenol A (BPA), an environmental endocrine-disrupting organic chemical, has been positively associated with the rate of implantation failure of in vitro fertilization. However, the underlying mechanisms remain unclear. To reveal the impact and the underlying mechanism of BPA on the crosstalk between trophoblast and decidual stromal cells (DSCs), we determined whether BPA was able to affect trophoblast invasion in vitro. We found that BPA significantly inhibited CXCL8 expression in DSCs, which hindered trophoblast invasion, and activated the phosphorylation of ERK in DSCs. U0126, an inhibitor of ERK activation, remarkably rescued trophoblast invasion and the inhibition of CXCL8 expression caused by BPA treatment. Moreover, the nuclear estrogen receptor antagonist ICI 182,780 and transmembrane G protein-coupled receptor GPR30 (membrane estrogen receptor) antagonist G15 significantly blocked the phosphorylation of ERK and reversed the reduction of trophoblast invasion. In brief, BPA activated ERK through nuclear and membrane estrogen receptors and inhibited CXCL8 expression in DSCs, thereby affecting their regulation of trophoblast invasion.
http://ift.tt/2uHu8Yo
Pregnancy in Women with Non-Classic Congenital Adrenal Hyperplasia: Time to Conceive and Outcome
Summary
Objective
Non-classic congenital adrenal hyperplasia (NCAH) is common among Ashkenazi Jews (1:400). It is associated with various degrees of postnatal virilization, irregular menses and infertility. Therapy of symptomatic subjects consists of physiologic doses of glucocorticoids. The objective of this study was to evaluate the effect of glucocorticoid treatment on fertility and on pregnancy outcome in women with NCAH.
Design, Setting and Patients
This retrospective study included 75 women diagnosed with NCAH who were followed in our clinic and sought fertility between 2008 and 2015.
Results
Seventy-two women succeeded in conceiving (187 pregnancies). Time to conception was 4.0±7 months without and 3.3±3 months with glucocorticoid therapy (P=0.43). Seventeen pregnancies were achieved by glucocorticoid therapy after failure to conceive spontaneously. Time to conception before therapy initiation was 10.2±11.4 months compared to 3.3 ± 3.4 months after therapy initiation (P=0.02). Out of 187 pregnancies, 135 (72%) resulted in live births, 38 (20.3%) ended in spontaneous miscarriages during the first trimester, 7 (3.7%) were electively terminated, 3 (1.6%) were ectopic, and 4 (2.1%) were ongoing during the study with similar rate in glucocorticoid treated and untreated pregnancies.
Conclusions
The 96% pregnancy rate among our cohort of NCAH females was similar to the 95% rate reported for the normal population. Glucocorticoid therapy may shorten the time to conceive in a subgroup of women with NCAH. Glucocorticoid therapy did not affect the rate of first trimester miscarriage. Our 77% live birth rate was similar to the 72% live birth rate in the current healthy US population
This article is protected by copyright. All rights reserved.
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Methods for Automatic Detection of Artifacts in Microelectrode Recordings
Publication date: Available online 20 July 2017
Source:Journal of Neuroscience Methods
Author(s): Eduard Bakštein, Tomáš Sieger, Jiří Wild, Daniel Nova'k, Jakub Schneider, Pavel Vostatek, Dušan Urgošík, Robert Jech
BackgroundExtracellular microelectrode recording (MER) is a prominent technique for studies of extracellular single-unit neuronal activity. In order to achieve robust results in more complex analysis pipelines, it is necessary to have high quality input data with a low amount of artifacts. We show that noise (mainly electromagnetic interference and motion artifacts) may affect more than 25% of the recording length in a clinical MER database.New MethodWe present several methods for automatic detection of noise in MER signals, based on i) unsupervised detection of stationary segments, ii) large peaks in the power spectral density, and iii) a classifier based on multiple time- and frequency-domain features. We evaluate the proposed methods on a manually annotated database of 5735 ten-second MER signals from 58 Parkinson's disease patients.Comparison with Existing MethodsThe existing methods for artifact detection in single-channel MER that have been rigorously tested, are based on unsupervised change-point detection. We show on an extensive real MER database that the presented techniques are better suited for the task of artifact identification and achieve much better results.ResultsThe best-performing classifiers (bagging and decision tree) achieved artifact classification accuracy of up to 89% on an unseen test set and outperformed the unsupervised techniques by 5-10%. This was close to the level of agreement among raters using manual annotation (93.5%).ConclusionWe conclude that the proposed methods are suitable for automatic MER denoising and may help in the efficient elimination of undesirable signal artifacts.
Graphical abstract
Highlights
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Biomarkers as a treatment guide in rheumatoid arthritis
Source:Clinical Immunology
Author(s): Tsutomu Takeuchi
It is anticipated that biomarkers support rheumatologists to judge a group of patients that can improve the diagnosis and prognosis, and further facilitate appropriate and precise treatment with targeted therapy. In particular, biomarkers for predicting and monitoring response to biological disease modifying anti-rheumatic drugs (DMARDs) are demanding. Given the mechanism action of biological DMARDs is much more simple than the conventional synthetic DMARDs, a variety of approaches to find such biomarkers has been taken recent years. In this article, I will summarize the background for biomarker research and introduce recent topics in the research and the possible clinical applications of biomarkers to guide treatment in rheumatoid arthritis (RA).
http://ift.tt/2uQtNmy
B-cells as therapeutic targets in neuro-inflammatory diseases
Source:Clinical Immunology
Author(s): Reinhard Hohlfeld
B cells are an emerging therapeutic target in neuroinflammatory diseases. The anti-CD20 monoclonal antibody ocrelizumab was recently approved in the US as the first B-cell targeting immunomodulatory treatment for relapsing-remitting MS and primary progressive MS. In autoantibody-associated demyelinating syndromes such as neuromyelitis optica (NMO) and in myelin-oligodendrocyte-glycoprotein-(MOG)-autoantibody-associated encephalomyelitis, B-cells are a logical target based on the pathogenesis of these antibody-mediated disorders. Furthermore, B cells and autoantibodies are promising targets in a variety of autoantibody-associated encephalitis syndromes such as N-methyl-d-aspartate receptor (NMDAR)-antibody encephalitis.
http://ift.tt/2vsiJcE
Efficacy paradox and proportional contextual effect (PCE)
Source:Clinical Immunology
Author(s): Weiya Zhang, Michael Doherty
The "efficacy paradox" is when the effect of a treatment tested in an RCT, or evidence-based guideline advice, differs markedly from treatment benefits observed in clinical practice. This arises because in RCT reporting and guideline development treatment efficacy is judged by the separation of the treatment group from the placebo group (the specific treatment effect) whereas in clinical practice it is the overall treatment effect, which includes both specific and contextual responses, that patients experience. This paradox causes a disconnect between guidelines and clinical practice and ignores the importance of contextual response in clinical care. This article fully explains and discusses these issues and presents a possible way to reduce the paradox through an alteration in RCT reporting that shifts the focus to overall treatment benefit and the proportion ("proportional contextual effect") that is explained by placebo and contextual effects.
http://ift.tt/2uQocNj
Oral treatment with foralumab, a fully human anti-CD3 monoclonal antibody, prevents skin xenograft rejection in humanized mice
Source:Clinical Immunology
Author(s): Mineko Ogura, Songyan Deng, Paula Preston-Hurlburt, Hideki Ogura, Kunwar Shailubhai, Chantal Kuhn, Howard L. Weiner, Kevan C. Herold
Oral administration of biologics may be a feasible approach for immune therapy that improves drug safety and potentiates mechanisms of tolerance at mucosal barriers. We tested the ability of a fully human non-FcR binding anti-CD3 mAb, foralumab, to prevent skin xenograft rejection in mice with human immune systems. At an intragastric dose of 15μg, the drug could transit through the small bowel. Serum absorption and binding of lymphoid cells was seen and proliferative responses of splenic CD8+ T cells to mitogen were reduced. Five consecutive daily doses, then weekly dosing led to indefinite graft acceptance without depletion of peripheral T cells. Proliferative and cytokine responses to activation of splenocytes with PHA were reduced. The serum levels of IL-10 but not TNF were increased 6days after application of the skin graft. Oral treatment with anti-CD3 mAb may represent a feasible approach for immune modulation.
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Solving the pathogenesis of ankylosing spondylitis
Source:Clinical Immunology
Author(s): Matthew A. Brown
http://ift.tt/2uQtKXU
Dendritic cells activation is associated with sustained virological response to telaprevir treatment of HCV-infected patients
Source:Clinical Immunology
Author(s): Sacchi Alessandra, Tumino Nicola, Turchi Federica, Refolo Giulia, Fimia GianMaria, Ciccosanti Fabiola, Montalbano Marzia, Lionetti Raffaella, Taibi Chiara, D'Offizi Gianpiero, Casetti Rita, Bordoni Veronica, Cimini Eleonora, Martini Federico, Agrati Chiara
First anti-HCV treatments, that include protease inhibitors in conjunction with IFN-α and Ribavirin, increase the sustained virological response (SVR) up to 80% in patients infected with HCV genotype 1. The effects of triple therapies on dendritic cell (DC) compartment have not been investigated. In this study we evaluated the effect of telaprevir-based triple therapy on DC phenotype and function, and their possible association with treatment outcome.HCV+ patients eligible for telaprevir-based therapy were enrolled, and circulating DC frequency, phenotype, and function were evaluated by flow-cytometry. The antiviral activity of plasmacytoid DC was also tested.In SVR patients, myeloid DC frequency transiently decreased, and returned to baseline level when telaprevir was stopped. Moreover, an up-regulation of CD80 and CD86 on mDC was observed in SVR patients as well as an improvement of IFN-α production by plasmacytoid DC, able to inhibit in vitro HCV replication.
http://ift.tt/2vsezBo
Rheumatic paraneoplastic syndromes – A clinical link between malignancy and autoimmunity
Source:Clinical Immunology
Author(s): Bernhard Manger, Georg Schett
Paraneoplastic syndromes are rare but can have enormous clinical impact on diagnosis and outcome of neoplastic diseases. The rheumatologist should be familiar with a few typical musculoskeletal manifestations of malignancies to be able to diagnose them early for a timely initiation of anti-tumour therapies. This review describes the characteristic features of various paraneoplastic arthritides and vasculitides, cancer-associated myositis, hypertrophic osteoarthropathy, and tumour-induced osteomalacia. In addition, the current knowledge about underlying pathomechanisms of these syndromes is discussed.
http://ift.tt/2uQhKWu
miRNA meets plasma cells “How tiny RNAs control antibody responses”
Source:Clinical Immunology
Author(s): Julia Meinzinger, Hans-Martin Jäck, Katharina Pracht
We review the importance of small non-coding microRNAs for the generation of germinal center B cells and their differentiation in antibody-secreting plasma cells. In the last part, we briefly elucidate the role of microRNAs in some plasma cell disorders.
http://ift.tt/2vs0PXe
B cells and their cytokine activities implications in human diseases
Source:Clinical Immunology
Author(s): Simon Fillatreau
B cells are the only cell type that can give rise to antibody-producing cells, and the only cell type whose selective depletion can, today, lead to an improvement of a wide range of immune-mediated inflammatory diseases, including disorders not primarily driven by autoantibodies. Here, I discuss this paradoxical observation, and propose that the capacity of B cells to act as cytokine-producing cells explains how they can control monocyte activity and subsequently disease pathogenesis. Together with current data on the effect of anti-CD20 B cell-depleting reagents in the clinic, this novel knowledge on B cell heterogeneity opens the way for novel safer and more efficient strategies to target B cells. The forthcoming identification of disease-relevant B cell subsets is awaited to permit their monitoring and specific targeting in a personalized medicine approach.
http://ift.tt/2uQ6OrX
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