963 research outputs found

    Human Multipotent Stromal Cells (MSCs) Increase Neurogenesis and Decrease Atrophy of the Striatum in a Transgenic Mouse Model for Huntington's Disease

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    Background: Implantation of human multipotent stromal cells from bone marrow (hMSCs) into the dentate gyrus of the hippocampus of mice was previously shown to stimulate proliferation, migration and neural differentiation of endogenous neural stem cells. We hypothesized that hMSCs would be beneficial in a mouse model of Huntington disease (HD) due to these neurogenic effects. Results: We implanted hMSCs into the striatum of transgenic mice (N171-82Q) that are a model for HD. The implanted hMSCs rapidly disappeared over 3 to 15 days. However, they increased proliferation and neural differentiation of endogenous neural stem cells for up to 30 days. They also increased neurotrophic signaling and decreased atrophy of the striatum in 3-month old HD mice implanted with hMSCs one month earlier. Conclusions: The results therefore suggested that neural implantation of hMSCs may be of benefit in HD but a number of parameters of dose, treatment schedule, and route of administration need to be optimized

    Diabetes in pregnancy among indigenous women in Australia, Canada, New Zealand, and the United States: a method for systematic review of studies with different designs

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    <p>Abstract</p> <p>Background</p> <p>Diabetes in pregnancy, which includes gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM), is associated with poor outcomes for both mother and infant during pregnancy, at birth and in the longer term. Recent international guidelines recommend changes to the current GDM screening criteria. While some controversy remains, there appears to be consensus that women at high risk of T2DM, including indigenous women, should be offered screening for GDM early in pregnancy, rather than waiting until 24-28 weeks as is current practice. A range of criteria should be considered before changing screening practice in a population sub-group, including: prevalence, current practice, acceptability and whether adequate treatment pathways and follow-up systems are available. There are also specific issues related to screening in pregnancy and indigenous populations. The evidence that these criteria are met for indigenous populations is yet to be reported. A range of study designs can be considered to generate relevant evidence for these issues, including epidemiological, observational, qualitative, and intervention studies, which are not usually included within a single systematic review. The aim of this paper is to describe the methods we used to systematically review studies of different designs and present the evidence in a pragmatic format for policy discussion.</p> <p>Methods/Design</p> <p>The inclusion criteria will be broad to ensure inclusion of the critical perspectives of indigenous women. Abstracts of the search results will be reviewed by two persons; the full texts of all potentially eligible papers will be reviewed by one person, and 10% will be checked by a second person for validation. Data extraction will be standardised, using existing tools to identify risks for bias in intervention, measurement, qualitative studies and reviews; and adapting criteria for appraising risk for bias in descriptive studies. External validity (generalisability) will also be appraised. The main findings will be synthesised according to the criteria for population-based screening and summarised in an adapted "GRADE" tool.</p> <p>Discussion</p> <p>This will be the first systematic review of all the published literature on diabetes in pregnancy among indigenous women. The method provides a pragmatic approach for synthesizing relevant evidence from a range of study designs to inform the current policy discussion.</p

    Cyclical changes in seroprevalence of leptospirosis in California sea lions: endemic and epidemic disease in one host species?

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    BackgroundLeptospirosis is a zoonotic disease infecting a broad range of mammalian hosts, and is re-emerging globally. California sea lions (Zalophus californianus) have experienced recurrent outbreaks of leptospirosis since 1970, but it is unknown whether the pathogen persists in the sea lion population or is introduced repeatedly from external reservoirs.MethodsWe analyzed serum samples collected over an 11-year period from 1344 California sea lions that stranded alive on the California coast, using the microscopic agglutination test (MAT) for antibodies to Leptospira interrogans serovar Pomona. We evaluated seroprevalence among yearlings as a measure of incidence in the population, and characterized antibody persistence times based on temporal changes in the distribution of titer scores. We conducted multinomial logistic regression to determine individual risk factors for seropositivity with high and low titers.ResultsThe serosurvey revealed cyclical patterns in seroprevalence to L. interrogans serovar Pomona, with 4-5 year periodicity and peak seroprevalence above 50%. Seroprevalence in yearling sea lions was an accurate index of exposure among all age classses, and indicated on-going exposure to leptospires in non-outbreak years. Analysis of titer decay rates showed that some individuals probably maintain high titers for more than a year following exposure.ConclusionThis study presents results of an unprecedented long-term serosurveillance program in marine mammals. Our results suggest that leptospirosis is endemic in California sea lions, but also causes periodic epidemics of acute disease. The findings call into question the classical dichotomy between maintenance hosts of leptospirosis, which experience chronic but largely asymptomatic infections, and accidental hosts, which suffer acute illness or death as a result of disease spillover from reservoir species

    The Novel Ό-Opioid Receptor Antagonist GSK1521498 Decreases Both Alcohol Seeking and Drinking: Evidence from a New Preclinical Model of Alcohol Seeking.

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    Distinct environmental and conditioned stimuli influencing ethanol-associated appetitive and consummatory behaviors may jointly contribute to alcohol addiction. To develop an effective translational animal model that illuminates this interaction, daily seeking responses, maintained by alcohol-associated conditioned stimuli (CSs), need to be dissociated from alcohol drinking behavior. For this, we established a procedure whereby alcohol seeking maintained by alcohol-associated CSs is followed by a period during which rats have the opportunity to drink alcohol. This cue-controlled alcohol-seeking procedure was used to compare the effects of naltrexone and GSK1521498, a novel selective ÎŒ-opioid receptor antagonist, on both voluntary alcohol-intake and alcohol-seeking behaviors. Rederived alcohol-preferring, alcohol-nonpreferring, and high-alcohol-drinking replicate 1 line of rats (Indiana University) first received 18 sessions of 24 h home cage access to 10% alcohol and water under a 2-bottle choice procedure. They were trained subsequently to respond instrumentally for access to 15% alcohol under a second-order schedule of reinforcement, in which a prolonged period of alcohol-seeking behavior was maintained by contingent presentations of an alcohol-associated CS acting as a conditioned reinforcer. This seeking period was terminated by 20 min of free alcohol drinking access that achieved significant blood alcohol concentrations. The influence of pretreatment with either naltrexone (0.1-1-3 mg/kg) or GSK1521498 (0.1-1-3 mg/kg) before instrumental sessions was measured on both seeking and drinking behaviors, as well as on drinking in the 2-bottle choice procedure. Naltrexone and GSK1521498 dose-dependently reduced both cue-controlled alcohol seeking and alcohol intake in the instrumental context as well as alcohol intake in the choice procedure. However, GSK1521498 showed significantly greater effectiveness than naltrexone, supporting its potential use for promoting abstinence and preventing relapse in alcohol addiction.The present study was funded by Medical Research Council Programme Grant (no. G1002231) and by GlaxoSmithKline (GSK), which has a commercial interest in GSK1521498. Charles R. Goodlett was funded by a grant from the IUPUI International Development Fund, which supported his sabbatical leave at the University of Cambridge. Maria Pilar Garcia-Pardo was funded by Val+id para investigadores en formaciĂłn (Conselleria de educacion, Generalitat Valenciana), which also supported her stay at the University of Cambridge (January-April 2014) as a Visiting Student.This is the accepted manuscript. The final version is available from NPG at http://dx.doi.org/10.1038/npp.2015.15

    Measurement of the Forward-Backward Asymmetry in the B -> K(*) mu+ mu- Decay and First Observation of the Bs -> phi mu+ mu- Decay

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    We reconstruct the rare decays B+→K+ÎŒ+Ό−B^+ \to K^+\mu^+\mu^-, B0→K∗(892)0ÎŒ+Ό−B^0 \to K^{*}(892)^0\mu^+\mu^-, and Bs0→ϕ(1020)ÎŒ+Ό−B^0_s \to \phi(1020)\mu^+\mu^- in a data sample corresponding to 4.4fb−14.4 {\rm fb^{-1}} collected in ppˉp\bar{p} collisions at s=1.96TeV\sqrt{s}=1.96 {\rm TeV} by the CDF II detector at the Fermilab Tevatron Collider. Using 121±16121 \pm 16 B+→K+ÎŒ+Ό−B^+ \to K^+\mu^+\mu^- and 101±12101 \pm 12 B0→K∗0ÎŒ+Ό−B^0 \to K^{*0}\mu^+\mu^- decays we report the branching ratios. In addition, we report the measurement of the differential branching ratio and the muon forward-backward asymmetry in the B+B^+ and B0B^0 decay modes, and the K∗0K^{*0} longitudinal polarization in the B0B^0 decay mode with respect to the squared dimuon mass. These are consistent with the theoretical prediction from the standard model, and most recent determinations from other experiments and of comparable accuracy. We also report the first observation of the Bs0→ϕΌ+Ό−decayandmeasureitsbranchingratioB^0_s \to \phi\mu^+\mu^- decay and measure its branching ratio {\mathcal{B}}(B^0_s \to \phi\mu^+\mu^-) = [1.44 \pm 0.33 \pm 0.46] \times 10^{-6}using using 27 \pm 6signalevents.Thisiscurrentlythemostrare signal events. This is currently the most rare B^0_s$ decay observed.Comment: 7 pages, 2 figures, 3 tables. Submitted to Phys. Rev. Let

    Serological evidence for transmission of multiple dengue virus serotypes in Papua New Guinea and West Papua prior to 1963

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    Little is known about the natural history of dengue in Papua New Guinea (PNG). We assessed dengue virus (DENV)-specific neutralizing antibody profiles in serum samples collected from northern and southern coastal areas and the highland region of New Guinea between 1959 and 1963. Neutralizing antibodies were demonstrated in sera from the northern coast of New Guinea: from Sabron in Dutch New Guinea (now known as West Papua) and from four villages in East Sepik in what is now PNG. Previous monotypic infection with DENV-1, DENV-2, and DENV-4 was identified, with a predominance of anti-DENV-2 neutralizing antibody. The majority of positive sera demonstrated evidence of multiple previous DENV infections and neutralizing activity against all four serotypes was detected, with anti-DENV-2 responses being most frequent and of greatest magnitude. No evidence of previous DENV infection was identified in the Asmat villages of the southern coast and a single anti-DENV-positive sample was identified in the Eastern Highlands of PNG. These findings indicate that multiple DENV serotypes circulated along the northern coast of New Guinea at different times in the decades prior to 1963 and support the notion that dengue has been a significant yet neglected tropical infection in PNG for many decades

    Measurements of the properties of Lambda_c(2595), Lambda_c(2625), Sigma_c(2455), and Sigma_c(2520) baryons

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    We report measurements of the resonance properties of Lambda_c(2595)+ and Lambda_c(2625)+ baryons in their decays to Lambda_c+ pi+ pi- as well as Sigma_c(2455)++,0 and Sigma_c(2520)++,0 baryons in their decays to Lambda_c+ pi+/- final states. These measurements are performed using data corresponding to 5.2/fb of integrated luminosity from ppbar collisions at sqrt(s) = 1.96 TeV, collected with the CDF II detector at the Fermilab Tevatron. Exploiting the largest available charmed baryon sample, we measure masses and decay widths with uncertainties comparable to the world averages for Sigma_c states, and significantly smaller uncertainties than the world averages for excited Lambda_c+ states.Comment: added one reference and one table, changed order of figures, 17 pages, 15 figure

    Search for a New Heavy Gauge Boson Wprime with Electron + missing ET Event Signature in ppbar collisions at sqrt(s)=1.96 TeV

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    We present a search for a new heavy charged vector boson Wâ€ČW^\prime decaying to an electron-neutrino pair in ppˉp\bar{p} collisions at a center-of-mass energy of 1.96\unit{TeV}. The data were collected with the CDF II detector and correspond to an integrated luminosity of 5.3\unit{fb}^{-1}. No significant excess above the standard model expectation is observed and we set upper limits on σ⋅B(Wâ€Č→eÎœ)\sigma\cdot{\cal B}(W^\prime\to e\nu). Assuming standard model couplings to fermions and the neutrino from the Wâ€ČW^\prime boson decay to be light, we exclude a Wâ€ČW^\prime boson with mass less than 1.12\unit{TeV/}c^2 at the 95\unit{%} confidence level.Comment: 7 pages, 2 figures Submitted to PR
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