495 research outputs found
Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation
FUNDING AND DISCLOSURE The research was funded by Wellcome Trust (WT098012) to LKH; and National Institute of Health (DK056731) and the Marilyn H. Vincent Foundation to MGM. The University of Michigan Transgenic Core facility is partially supported by the NIH-funded University of Michigan Center for Gastrointestinal Research (DK034933). The remaining authors declare no conflict of interest. ACKNOWLEDGMENTS We thank Dr Celine Cansell, Ms Raffaella Chianese and the staff of the Medical Research Facility for technical assistance. We thank Dr Vladimir Orduña for the scientific advice and technical assistance.Peer reviewedPublisher PD
The Effects of Cocaine on Different Redox Forms of Cysteine and Homocysteine, and on Labile, Reduced Sulfur in the Rat Plasma Following Active versus Passive Drug Injections
Received: 28 November 2012 / Revised: 19 April 2013 / Accepted: 6 May 2013 / Published online: 16 May 2013
The Author(s) 2013. This article is published with open access at Springerlink.comThe aim of the present studies was to evaluate
cocaine-induced changes in the concentrations of different
redox forms of cysteine (Cys) and homocysteine (Hcy),
and products of anaerobic Cys metabolism, i.e., labile,
reduced sulfur (LS) in the rat plasma. The above-mentioned
parameters were determined after i.p. acute and
subchronic cocaine treatment as well as following i.v.
cocaine self-administration using the yoked procedure.
Additionally, Cys, Hcy, and LS levels were measured
during the 10-day extinction training in rats that underwent
i.v. cocaine administration. Acute i.p. cocaine treatment
increased the total and protein-bound Hcy contents,
decreased LS, and did not change the concentrations of Cys
fractions in the rat plasma. In turn, subchronic i.p. cocaine administration significantly increased free Hcy and lowered
the total and protein-bound Cys concentrations while
LS level was unchanged. Cocaine self-administration
enhanced the total and protein-bound Hcy levels, decreased
LS content, and did not affect the Cys fractions. On the
other hand, yoked cocaine infusions did not alter the concentration
of Hcy fractions while decreased the total and
protein-bound Cys and LS content. This extinction training
resulted in the lack of changes in the examined parameters
in rats with a history of cocaine self-administration while in
the yoked cocaine group an increase in the plasma free Cys
fraction and LS was seen. Our results demonstrate for the
first time that cocaine does evoke significant changes in
homeostasis of thiol amino acids Cys and Hcy, and in some
products of anaerobic Cys metabolism, which are dependent
on the way of cocaine administration
Practical Tools to Implement Massive Parallel Pyrosequencing of PCR Products in Next Generation Molecular Diagnostics
Despite improvements in terms of sequence quality and price per basepair, Sanger sequencing remains restricted to screening of individual disease genes. The development of massively parallel sequencing (MPS) technologies heralded an era in which molecular diagnostics for multigenic disorders becomes reality. Here, we outline different PCR amplification based strategies for the screening of a multitude of genes in a patient cohort. We performed a thorough evaluation in terms of set-up, coverage and sequencing variants on the data of 10 GS-FLX experiments (over 200 patients). Crucially, we determined the actual coverage that is required for reliable diagnostic results using MPS, and provide a tool to calculate the number of patients that can be screened in a single run. Finally, we provide an overview of factors contributing to false negative or false positive mutation calls and suggest ways to maximize sensitivity and specificity, both important in a routine setting. By describing practical strategies for screening of multigenic disorders in a multitude of samples and providing answers to questions about minimum required coverage, the number of patients that can be screened in a single run and the factors that may affect sensitivity and specificity we hope to facilitate the implementation of MPS technology in molecular diagnostics
Histopathological cutaneous alterations in systemic sclerosis: a clinicopathological study
Introduction: The aims of the present study were to identify histopathological parameters which are linked to local clinical skin disease at two distinct anatomical sites in systemic sclerosis (SSc) patients with skin involvement (limited cutaneous systemic sclerosis (lcSSc) or diffuse cutaneous systemic sclerosis (dcSSc)) and to determine the sensitivity of SSc specific histological alterations, focusing on SSc patients without clinical skin involvement (limited SSc (lSSc)).
Methods: Histopathological alterations were systematically scored in skin biopsies of 53 consecutive SSc patients (dorsal forearm and upper inner arm) and 18 controls (upper inner arm). Clinical skin involvement was evaluated using the modified Rodnan skin score. In patients with lcSSc or dcSSc, associations of histopathological parameters with local clinical skin involvement were determined by generalised estimation equation modelling.
Results: The hyalinised collagen score, the myofibroblast score, the mean epidermal thickness, the mononuclear cellular infiltration and the frequency of focal exocytosis differed significantly between biopsies with and without local clinical skin involvement. Except for mononuclear cellular infiltration, all of the continuous parameters correlated with the local clinical skin score at the dorsal forearm. Parakeratosis, myofibroblasts and intima proliferation were present in a minority of the SSc biopsies, but not in controls. No differences were found between lSSc and controls.
Conclusions: Several histopathological parameters are linked to local clinical skin disease. SSc-specific histological alterations have a low diagnostic sensitivity
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Reply to: New Meta- and Mega-analyses of Magnetic Resonance Imaging Findings in Schizophrenia: Do They Really Increase Our Knowledge About the Nature of the Disease Process?
This work was supported by National Institute of Biomedical Imaging and Bioengineering Grant No. U54EB020403 (to the ENIGMA consortium)
Azimuthal anisotropy and correlations at large transverse momenta in and Au+Au collisions at = 200 GeV
Results on high transverse momentum charged particle emission with respect to
the reaction plane are presented for Au+Au collisions at =
200 GeV. Two- and four-particle correlations results are presented as well as a
comparison of azimuthal correlations in Au+Au collisions to those in at
the same energy. Elliptic anisotropy, , is found to reach its maximum at
GeV/c, then decrease slowly and remain significant up to
-- 10 GeV/c. Stronger suppression is found in the back-to-back
high- particle correlations for particles emitted out-of-plane compared to
those emitted in-plane. The centrality dependence of at intermediate
is compared to simple models based on jet quenching.Comment: 4 figures. Published version as PRL 93, 252301 (2004
Azimuthal anisotropy in Au+Au collisions at sqrtsNN = 200 GeV
The results from the STAR Collaboration on directed flow (v_1), elliptic flow
(v_2), and the fourth harmonic (v_4) in the anisotropic azimuthal distribution
of particles from Au+Au collisions at sqrtsNN = 200 GeV are summarized and
compared with results from other experiments and theoretical models. Results
for identified particles are presented and fit with a Blast Wave model.
Different anisotropic flow analysis methods are compared and nonflow effects
are extracted from the data. For v_2, scaling with the number of constituent
quarks and parton coalescence is discussed. For v_4, scaling with v_2^2 and
quark coalescence is discussed.Comment: 26 pages. As accepted by Phys. Rev. C. Text rearranged, figures
modified, but data the same. However, in Fig. 35 the hydro calculations are
corrected in this version. The data tables are available at
http://www.star.bnl.gov/central/publications/ by searching for "flow" and
then this pape
Rapidity and Centrality Dependence of Proton and Anti-proton Production from Au+Au Collisions at sqrt(sNN) = 130GeV
We report on the rapidity and centrality dependence of proton and anti-proton
transverse mass distributions from Au+Au collisions at sqrt(sNN) = 130GeV as
measured by the STAR experiment at RHIC. Our results are from the rapidity and
transverse momentum range of |y|<0.5 and 0.35 <p_t<1.00GeV/c. For both protons
and anti-protons, transverse mass distributions become more convex from
peripheral to central collisions demonstrating characteristics of collective
expansion. The measured rapidity distributions and the mean transverse momenta
versus rapidity are flat within |y|<0.5. Comparisons of our data with results
from model calculations indicate that in order to obtain a consistent picture
of the proton(anti-proton) yields and transverse mass distributions the
possibility of pre-hadronic collective expansion may have to be taken into
account.Comment: 4 pages, 3 figures, 1 table, submitted to PR
Screening and early psychological intervention for depression in schools: systematic review and meta-analysis.
Abstract Depression in children and adolescents is considerably undertreated, and the school may be a good setting for identifying and treating depression. We conducted a meta-analysis of studies in which students were screened for depression, and those with depressive symptoms were treated with a psychological intervention. Only randomised controlled trials were included. Eight studies met the inclusion criteria. Five studies focused on younger children (7–14 years) and three studies were aimed at adolescents (12–19 years). In total 5803 students were screened, of whom 7.2% were included in the intervention studies (95% CI: 7.1–7.3). The ‘numbers-needed-to-screen’ was 31 (95% CI: 27–32), which means that 31 students had to be screened in order to generate one successfully treated case of depression. The effects of the psychological treatments at posttest were compared to control conditions in the 8 studies comprising 12 contrast groups, with a total of 413 students. The mean effect size was 0.55 (95% CI: 0.35– 0.76). There were not enough studies to examine whether specific psychotherapies were superior to other psychotherapies. Although the number of studies is small and their quality is limited, screening and early intervention at schools may be an effective strategy to reduce the burden of disease from depression in children and adolescents. More research on the (negative) effects of these interventions is needed
Non-fatal disease burden for subtypes of depressive disorder: population-based epidemiological study
Background: Major depression is the leading cause of non-fatal disease burden. Because major depression is not a homogeneous condition, this study estimated the non-fatal disease burden for mild, moderate and severe depression in both single episode and recurrent depression. All estimates were assessed from an individual and a population perspective and presented as unadjusted, raw estimates and as estimates adjusted for comorbidity. Methods: We used data from the first wave of the second Netherlands-Mental-Health-Survey-and-Incidence-Study (NEMESIS-2, n = 6646; single episode Diagnostic and Statistical Manual (DSM)-IV depression, n = 115; recurrent depression, n = 246). Disease burden from an individual perspective was assessed as 'disability weight * time spent in depression' for each person in the dataset. From a population perspective it was assessed as 'disability weight * time spent in depression *number of people affected'. The presence of mental disorders was assessed with the Composite International Diagnostic Interview (CIDI) 3.0. Results: Single depressive episodes emerged as a key driver of disease burden from an individual perspective. From a population perspective, recurrent depressions emerged as a key driver. These findings remained unaltered after adjusting for comorbidity. Conclusions: The burden of disease differs between the subtype of depression and depends much on the choice of perspective. The distinction between an individual and a population perspective may help to avoid misunderstandings between policy makers and clinicians. © 2016 Biesheuvel-Leliefeld et al
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