Breakpoint mapping by whole genome sequencing identifies PTH2R gene disruption in a patient with midline craniosynostosis and a de novo balanced chromosomal rearrangement

Background: Craniosynostosis (CRS) is a premature closure of calvarial sutures caused by gene mutation or environmental factors or interaction between the two. Only a small proportion of non-syndromic CRS (NSC) patients have a known genetic cause, and thus, it would be meaningful to search for a causative gene disruption for the development NSC. We applied a whole genome sequencing approach on a 15-month-old boy with sagittal and metopic synostosis to identify a gene responsible for the development of the disease. Methods and results Conventional chromosome study revealed a complex paracentric inversion involving 2q14.3 and 2q34. Array comparative genomic hybridisation did not show any copy number variation. Multicolour banding analysis was carried out and the breakpoints were refined to 2q14 and 2q34. An intronic break of the PTH2R gene was detected by whole genome sequencing and fluorescence in situ hybridisation analysis confirmed disruption of PTH2R. Conclusions: We report PTH2R as a gene that is disrupted in NSC. The disruption of the PTH2R gene may cause uncontrolled proliferation and differentiation of chondrocytes, which in turn results in premature closure of sutures. This addition of PTH2R to the list of genes associated with NSC expands our understanding of the development of NSC

Self-esteem as a Moderator of the Effects of Happiness, Depression, and Hostility on Suicidality Among Early Adolescents in Korea

Objectives The purpose of this study was to investigate the role of self-esteem as a moderator of the factors influencing suicidality among middle-schoolers. Methods Moderated multiple regression analysis was applied to assess the influence of happiness, depression, and hostility on suicidality and to determine the degree to which self-esteem served as a moderator of those relationships. Data were collected from 268 students at a middle school in Busan, Korea, using a self-administered structured questionnaire. Results Happiness, depression, and hostility had significant direct effects on suicidality. Self-esteem showed no direct effect, but had a significant moderating effect on the relationship between hostility and suicidal behavior. Conclusions These results suggest that various interventions, such as counseling programs, should be designed to alleviate hostility and depression and to enhance happiness and self-esteem among early adolescents

The impact of dose of the angiotensin-receptor blocker valsartan on the post-myocardial infarction ventricular remodeling: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Angiotensin-converting enzyme inhibitors and the angiotensin-receptor blocker valsartan ameliorate ventricular remodeling after myocardial infarction (MI). Based on previous clinical trials, a maximum clinical dose is recommended in practical guidelines. Yet, has not been clearly demonstrated whether the recommended dose is more efficacious compared to the lower dose that is commonly used in clinical practice.</p> <p>Method/Design</p> <p>Valsartan in post-MI remodeling (VALID) is a randomized, open-label, single-blinded multicenter study designed to compare the efficacy of different clinical dose of valsartan on the post-MI ventricular remodeling. This study also aims to assess neurohormone change and clinical parameters of patients during the post-infarct period. A total of 1116 patients with left ventricular dysfunction following the first episode of acute ST-elevation MI are to be enrolled and randomized to a maximal tolerable dose (up to 320 mg/day) or usual dose (80 mg/day) of valsartan for 12 months in 2:1 ratio. Echocardiographic analysis for quantifying post-MI ventricular remodeling is to be conducted in central core laboratory. Clinical assessment and laboratory test are performed at fixed times.</p> <p>Discussion</p> <p>VALID is a multicenter collaborative study to evaluate the impact of dose of valsartan on the post-MI ventricular remodeling. The results of the study provide information about optimal dosing of the drug in the management of patients after MI. The results will be available by 2012.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01340326">NCT01340326</a></p

The Effect of Rush Immunotherapy with House Dust Mite in the Production of IL-5 and IFN-γ from the Peripheral Blood T Cells of Asthmatic Children

Although the mechanisms are unclear, rush immunotherapy (RIT) may be effective to treat allergic diseases. We investigated the long-term modifications of cellular immunity as a mechanism of RIT. The RIT group, included 15 house dust mite (HDM)-sensitized asthmatic children, received RIT only with Dermatophagoides farinae (Der f) and Dermatophagoides pteronyssinus (Der p), whereas the control group, consisted of 10 HDM-sensitized asthmatic children, did not receive RIT. The asthma symptom scores and the skin reactivities to Der f were measured. The cellular proliferative responses and intracellular interleukin (IL)-5 and interferon (IFN)-γ productions from peripheral blood T cells were also measured before, 8 weeks and 1 yr after RIT. The symptom scores, skin reactivity to Der f and cellular proliferative responses to Der f were decreased significantly after 8 weeks and maintained until 1 yr of RIT. The IFN-γ/IL-5 ratio of the CD3(+) and CD4(+) cells were increased significantly after 8 weeks and maintained until 1 yr of RIT, while there were no changes in the control group. These data indicate that the continuous functional modification from Th2 to Th1 phenotype of the CD4(+) T cells are developed after RIT in the asthmatic children sensitized with HDM

J/psi suppression at forward rapidity in Au+Au collisions at sqrt(s_NN)=39 and 62.4 GeV

We present measurements of the J/psi invariant yields in sqrt(s_NN)=39 and 62.4 GeV Au+Au collisions at forward rapidity (1.2<|y|<2.2). Invariant yields are presented as a function of both collision centrality and transverse momentum. Nuclear modifications are obtained for central relative to peripheral Au+Au collisions (R_CP) and for various centrality selections in Au+Au relative to scaled p+p cross sections obtained from other measurements (R_AA). The observed suppression patterns at 39 and 62.4 GeV are quite similar to those previously measured at 200 GeV. This similar suppression presents a challenge to theoretical models that contain various competing mechanisms with different energy dependencies, some of which cause suppression and others enhancement.Comment: 365 authors, 10 pages, 11 figures, 4 tables. Submitted to Phys. Rev. C. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Observation of direct-photon collective flow in sqrt(s_NN)=200 GeV Au+Au collisions

The second Fourier component v_2 of the azimuthal anisotropy with respect to the reaction plane was measured for direct photons at midrapidity and transverse momentum (p_T) of 1--13 GeV/c in Au+Au collisions at sqr(s_NN)=200 GeV. Previous measurements of this quantity for hadrons with p_T < 6 GeV/c indicate that the medium behaves like a nearly perfect fluid, while for p_T > 6 GeV/c a reduced anisotropy is interpreted in terms of a path-length dependence for parton energy loss. In this measurement with the PHENIX detector at the Relativistic Heavy Ion Collider we find that for p_T > 4 GeV/c the anisotropy for direct photons is consistent with zero, as expected if the dominant source of direct photons is initial hard scattering. However, in the p_T < 4 GeV/c region dominated by thermal photons, we find a substantial direct photon v_2 comparable to that of hadrons, whereas model calculations for thermal photons in this kinematic region significantly underpredict the observed v_2.Comment: 384 authors, 6 pages, 3 figures, and 1 table. Submitted to Phys. Rev. Lett. v2 has minor changes to match the submission version. Plain text data tables for the points plotted in the figures are publicly available at http://www.phenix.bnl.gov/phenix/WWW/info/data/ppg126_data.htm