Thymic stromal lymphopoietin (TSLP) is associated with allergic rhinitis in children with asthma

<p>Abstract</p> <p>Background</p> <p>Allergic rhinitis (AR) affects up to 80% of children with asthma and increases asthma severity. Thymic stromal lymphopoietin (TSLP) is a key mediator of allergic inflammation. The role of the TSLP gene (<it>TSLP</it>) in the pathogenesis of AR has not been studied.</p> <p>Objective</p> <p>To test for associations between variants in <it>TSLP</it>, <it>TSLP</it>-related genes, and AR in children with asthma.</p> <p>Methods</p> <p>We genotyped 15 single nucleotide polymorphisms (SNPs) in <it>TSLP, OX40L, IL7R</it>, and <it>RXRα </it>in three independent cohorts: 592 asthmatic Costa Rican children and their parents, 422 nuclear families of North American children with asthma, and 239 Swedish children with asthma. We tested for associations between these SNPs and AR. As we previously reported sex-specific effects for <it>TSLP</it>, we performed overall and sex-stratified analyses. We additionally performed secondary analyses for gene-by-gene interactions.</p> <p>Results</p> <p>Across the three cohorts, the T allele of <it>TSLP </it>SNP rs1837253 was undertransmitted in boys with AR and asthma as compared to boys with asthma alone. The SNP was associated with reduced odds for AR (odds ratios ranging from 0.56 to 0.63, with corresponding Fisher's combined P value of 1.2 × 10^-4). Our findings were significant after accounting for multiple comparisons. SNPs in <it>OX40L, IL7R</it>, and <it>RXRα </it>were not consistently associated with AR in children with asthma. There were nominally significant interactions between gene pairs.</p> <p>Conclusions</p> <p><it>TSLP </it>SNP rs1837253 is associated with reduced odds for AR in boys with asthma. Our findings support a role for <it>TSLP </it>in the pathogenesis of AR in children with asthma.</p

A Computational Approach to Analyze the Mechanism of Action of the Kinase Inhibitor Bafetinib

Prediction of drug action in human cells is a major challenge in biomedical research. Additionally, there is strong interest in finding new applications for approved drugs and identifying potential side effects. We present a computational strategy to predict mechanisms, risks and potential new domains of drug treatment on the basis of target profiles acquired through chemical proteomics. Functional protein-protein interaction networks that share one biological function are constructed and their crosstalk with the drug is scored regarding function disruption. We apply this procedure to the target profile of the second-generation BCR-ABL inhibitor bafetinib which is in development for the treatment of imatinib-resistant chronic myeloid leukemia. Beside the well known effect on apoptosis, we propose potential treatment of lung cancer and IGF1R expressing blast crisis

Obstetric Outcomes in Women With Turner Karyotype EDITORIAL COMMENT

There is concern over the high risk of cardiovascular complications, hypertensive disorders, and other adverse obstetric outcomes among pregnant women with Turner syndrome (TS). A diagnosis of TS is made in some women late in life or not at all. Spontaneous pregnancies are rare in women with TS and are associated with a high rate of complications, especially miscarriage. The use of assisted reproductive techniques is an option for these women; pregnancy and implantation rates after oocyte donation in women with TS seem to be comparable with those without TS who need this treatment. Few data are available on obstetric outcome in pregnant women with TS. The aim of this retrospective population-based cohort study was to compare maternal and neonatal outcomes among singleton pregnancies of women with and without TS. Data on births occurring between 1973 and 2007 from the Swedish Genetic Turner Register and the Swedish Medical Birth Register were cross-linked. Obstetric outcome in infants born to women with TS was compared with a reference group of 56,000 women from the general population. Mean gestational age and birth weight were adjusted for maternal age. Outcome in TS women with twins was described separately. A total of 115 women with TS gave birth to 208 children (202 singletons and 3 sets of twins) during the study period. The TS diagnosis was unknown in 52% of the women before the first delivery. Women in the TS group were older at the first delivery than women in the reference group; median age was 30 years and 26 years, respectively (P < 0.0001). There was a trend toward more women with TS having preeclampsia during their first pregnancy (6.3 vs. 3.0%; P = 0.07). One woman suffered from an aortic dissection during her second spontaneous pregnancy. Compared with the reference group, the median gestational age was shorter in children in the TS group (-6.4 days, P = 0.0067), and median birth weight was lower (-208 g, P = 0.001); however, no significant difference was found in median standard deviation scores for weight and length at birth. The rate of cesarean delivery was higher in the TS group than in the reference group (35.6% vs. 11.8%, respectively, P < 0.0001). There was no significant difference in birth defects between groups. These findings show that women with a TS karyotype have mostly favorable obstetric outcomes. Singletons of women with TS have a shorter gestational age but a similar size at birth. The data also show no difference in birth defects between women with and without TS

Turner karyotype and childbirth

Turner karyotype and childbirth Anna Hagman, Department of Obstetrics and Gynaecology, Institute of Clinical Sciences, the Sahlgrenska Academy, University of Gothenburg, Sweden, 2013. [email protected] Turner syndrome (TS) is a sex chromosome aberration and occurs in 1/2500 live born girls. One X chromosome is absent or structurally changed in all (monosomy) or some (mosaicism) of the cells. TS is characterized by short stature, ovarian failure and cardiac defects. Mortality is increased, mostly owing to cardiovascular disease and aortic dissection. Pregnancies in women with TS are rare, but have increased owing to oocyte donation (OD) and are reported to be of high risk. The aim of this thesis was to describe characteristics of mothers to girls with TS and characteristics of newborns with TS and to evaluate the obstetric and neonatal outcomes in women with Turner karyotype and whether the pregnancy increased morbidity after delivery. Characteristics of mothers giving birth to girls with TS from 1973-2006 and their newborns with TS were investigated in a study using the Swedish Genetic Turner Register (SGTR) and the Swedish Medical Register (MBR). Mothers to girls with TS were older and shorter than mothers from the general population. More girls with TS were born late preterm and were small for gestational age than controls. In a registry study, using the SGTR, the MBR, and the Cause of Death Register (CDR), 115 women with Turner karyotype who gave birth to 208 children (after both spontaneous and OD pregnancies) born 1973-2007, were studied. One woman had an aortic dissection. Singletons of women with Turner karyotype had lower gestational age, but similar size at birth and the rate of birth defects did not differ. In a Nordic, descriptive study on women with TS who had delivered after OD 106, women and 131 children born from 1992-2011 were included, and data from medical records were registered. The rate of hypertensive disorders during pregnancy was 35%. Life-threatening events occurred in four pregnancies (3.3%) including one with aortic dissection. The rate of preterm birth was 8% and low birth weight 9%. In a population-based registry study, mortality and morbidity in 124 women with Turner karyotype who had given birth from 1973-2010 was compared with women with Turner karyotype without childbirth and a control group from the MBR. The SGTR, the MBR, the National Patient Register, the CDR and Cancer Register were used. Morbidity and mortality in the total Turner group were increased as compared with the controls. Morbidity from cardiovascular diseases was increased before and during pregnancy but similar after more than one year after delivery and no deaths were seen. In conclusion, pregnancies in women with TS are high risk pregnancies owing to hypertensive disorders and aortic dissection. Neonatal outcomes in women with TS are generally reassuring. Women who gave birth to girls with TS were shorter and older. Key words: Turner syndrome, obstetric, neonatal outcome, Turner karyotype, pregnancy, maternal, neonatal characteristics. ISBN 978-91-628-8648-

A Bayesian analysis of the chromosome architecture of human disorders by integrating reductionist data

In this paper, we present a Bayesian approach to estimate a chromosome and a disorder network from the Online Mendelian Inheritance in Man (OMIM) database. In contrast to other approaches, we obtain statistic rather than deterministic networks enabling a parametric control in the uncertainty of the underlying disorder-disease gene associations contained in the OMIM, on which the networks are based. From a structural investigation of the chromosome network, we identify three chromosome subgroups that reflect architectural differences in chromosome-disorder associations that are predictively exploitable for a functional analysis of diseases

An Epidemiological Human Disease Network Derived from Disease Co-occurrence in Taiwan

Abstract In “classic” biomedical research, diseases have usually been studied individually. The pioneering human disease network (HDN) studies jointly consider a large number of diseases, analyse their interconnections, and provide a more comprehensive description of diseases. However, most of the existing HDN studies are based on molecular information and can only partially describe disease interconnections. Building on the unique Taiwan National Health Insurance Research Database (NHIRD), in this study, we construct the epidemiological HDN (eHDN), where two diseases are concluded as interconnected if their observed probability of co-occurrence deviating that expected under independence. Advancing from the existing HDN, the eHDN can also accommodate non-molecular connections and have more important practical implications. Building on the network construction, we examine important network properties such as connectivity, module, hub, and others and describe their temporal patterns. This study is among the first to systematically construct the eHDN and can have important implications for human disease research and health care and management