Dexmedetomidine is neuroprotective in an in vitro model for traumatic brain injury

<p>Abstract</p> <p>Background</p> <p>The α₂-adrenoreceptor agonist dexmedetomidine is known to provide neuroprotection under ischemic conditions. In this study we investigated whether dexmedetomidine has a protective effect in an <it>in vitro </it>model for traumatic brain injury.</p> <p>Methods</p> <p>Organotypic hippocampal slice cultures were subjected to a focal mechanical trauma and then exposed to varying concentrations of dexmedetomidine. After 72 h cell injury was assessed using propidium iodide. In addition, the effects of delayed dexmedetomidine application, of hypothermia and canonical signalling pathway inhibitors were examined.</p> <p>Results</p> <p>Dexmedetomidine showed a protective effect on traumatically injured hippocampal cells with a maximum effect at a dosage of 1 μM. This effect was partially reversed by the simultaneous administration of the ERK inhibitor PD98059.</p> <p>Conclusion</p> <p>In this TBI model dexmedetomidine had a significant neuroprotective effect. Our results indicate that activation of ERK might be involved in mediating this effect.</p

Diffractive Dijet Production at sqrt(s)=630 and 1800 GeV at the Fermilab Tevatron

We report a measurement of the diffractive structure function $F_{jj}^D$ of the antiproton obtained from a study of dijet events produced in association with a leading antiproton in $\bar pp$ collisions at $\sqrt s=630$ GeV at the Fermilab Tevatron. The ratio of $F_{jj}^D$ at $\sqrt s=630$ GeV to $F_{jj}^D$ obtained from a similar measurement at $\sqrt s=1800$ GeV is compared with expectations from QCD factorization and with theoretical predictions. We also report a measurement of the $\xi$ ($x$-Pomeron) and $\beta$ ($x$ of parton in Pomeron) dependence of $F_{jj}^D$ at $\sqrt s=1800$ GeV. In the region $0.035<\xi<0.095$, $|t|<1$ GeV$^2$ and $\beta<0.5$, $F_{jj}^D(\beta,\xi)$ is found to be of the form $\beta^{-1.0\pm 0.1} \xi^{-0.9\pm 0.1}$, which obeys $\beta$-$\xi$ factorization.Comment: LaTeX, 9 pages, Submitted to Phys. Rev. Letter

A Study of B0 -> J/psi K(*)0 pi+ pi- Decays with the Collider Detector at Fermilab

We report a study of the decays B0 -> J/psi K(*)0 pi+ pi-, which involve the creation of a u u-bar or d d-bar quark pair in addition to a b-bar -> c-bar(c s-bar) decay. The data sample consists of 110 1/pb of p p-bar collisions at sqrt{s} = 1.8 TeV collected by the CDF detector at the Fermilab Tevatron collider during 1992-1995. We measure the branching ratios to be BR(B0 -> J/psi K*0 pi+ pi-) = (8.0 +- 2.2 +- 1.5) * 10^{-4} and BR(B0 -> J/psi K0 pi+ pi-) = (1.1 +- 0.4 +- 0.2) * 10^{-3}. Contributions to these decays are seen from psi(2S) K(*)0, J/psi K0 rho0, J/psi K*+ pi-, and J/psi K1(1270)

Identification of rare de novo epigenetic variations in congenital disorders

Certain human traits such as neurodevelopmental disorders (NDs) and congenital anomalies (CAs) are believed to be primarily genetic in origin. However, even after whole-genome sequencing (WGS), a substantial fraction of such disorders remain unexplained. We hypothesize that some cases of ND-CA are caused by aberrant DNA methylation leading to dysregulated genome function. Comparing DNA methylation profiles from 489 individuals with ND-CAs against 1534 controls, we identify epivariations as a frequent occurrence in the human genome. De novo epivariations are significantly enriched in cases, while RNAseq analysis shows that epivariations often have an impact on gene expression comparable to loss-of-function mutations. Additionally, we detect and replicate an enrichment of rare sequence mutations overlapping CTCF binding sites close to epivariations, providing a rationale for interpreting non-coding variation. We propose that epivariations contribute to the pathogenesis of some patients with unexplained ND-CAs, and as such likely have diagnostic relevance.The authors are grateful to the patients and families who participated in this study and to the collaborators who supported patient recruitment. This work was supported by NIH grant HG006696 and research grant 6-FY13-92 from the March of Dimes to A.J.S., grant HL098123 to B.D.G. and A.J.S., Gulbenkian Programme for Advanced Medical Education and the Portuguese Foundation for Science and Technology (SFRH/BDINT/51549/ 2011, PIC/IC/83026/2007, PIC/IC/83013/2007, SFRH/BD/90167/2012, Portugal) to P.M., F.L., and M.B., by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013) to P.M., a Beatriu de Pinos Postdoctoral Fellowship to R.S.J. (2011BP-A00515), and a Seaver Foundation fellowship to S.D.R. The views expressed are those of the authors and do not necessarily reflect those of the National Heart, Lung, and Blood Institute or the National Institutes of Health. Research reported in this paper was supported by the Office of Research Infrastructure of the National Institutes of Health under award number S10OD018522. This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai.The authors are grateful to the patients and families who participated in this study and to the collaborators who supported patient recruitment. This work was supported by NIH grant HG006696 and research grant 6-FY13-92 from the March of Dimes to A.J.S., grant HL098123 to B.D.G. and A.J.S., Gulbenkian Programme for Advanced Medical Education and the Portuguese Foundation for Science and Technology (SFRH/BDINT/51549/ 2011, PIC/IC/83026/2007, PIC/IC/83013/2007, SFRH/BD/90167/2012, Portugal) to P.M., F.L., and M.B., by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013) to P.M., a Beatriu de Pinos Postdoctoral Fellowship to R.S.J. (2011BP-A00515), and a Seaver Foundation fellowship to S.D.R. The views expressed are those of the authors and do not necessarily reflect those of the National Heart, Lung, and Blood Institute or the National Institutes of Health. Research reported in this paper was supported by the Office of Research Infrastructure of the National Institutes of Health under award number S10OD018522. This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai

Background matching in the brown shrimp Crangon crangon : adaptive camouflage and behavioural-plasticity

A combination of burrowing behaviour and very efficient background matching makes the brown shrimp Crangon crangon almost invisible to potential predators and preys. This raises questions on how shrimp succeed in concealing themselves in the heterogeneous and dynamic estuarine habitats they inhabit and what type of environmental variables and behavioural factors affect their colour change abilities. Using a series of behavioural experiments, we show that the brown shrimp is capable of repeated fast colour adaptations (20% change in dark pigment cover within one hour) and that its background matching ability is mainly influenced by illumination and sediment colour. Novel insights are provided on the occurrence of non-adaptive (possibly stress) responses to background changes after long-time exposure to a constant background colour or during unfavourable conditions for burying. Shrimp showed high levels of intra- and inter-individual variation, demonstrating a complex balance between behavioural-plasticity and environmental adaptation. As such, the study of crustacean colour changes represents a valuable opportunity to investigate colour adaptations in dynamic habitats and can help us to identify the mayor environmental and behavioural factors influencing the evolution of animal background matching

Metal release from contaminated estuarine sediment under pH changes in the marine environment

The contaminant release from estuarine sediment due to pH changes was investigated using a modified CEN/TS 14429 pH-dependence leaching test. The test is performed in the range of pH values of 0-14 using deionised water and seawater as leaching solutions. The experimental conditions mimic different circumstances of the marine environment due to the global acidification, carbon dioxide (CO2) leakages from carbon capture and sequestration technologies, and accidental chemical spills in seawater. Leaching test results using seawater as leaching solution show a better neutralisation capacity giving slightly lower metal leaching concentrations than when using deionised water. The contaminated sediment shows a low base-neutralisation capacity (BNCpH 12 = -0.44 eq/kg for deionised water and BNCpH 12 = -1.38 eq/kg for seawater) but a high acid-neutralisation capacity when using deionised water (ANCpH 4 = 3.58 eq/ kg) and seawater (ANCpH 4 = 3.97 eq/kg). Experimental results are modelled with the Visual MINTEQ geochemical software to predict metal release from sediment using both leaching liquids. Surface adsorption to iron- and aluminium- (hydr)oxides was applied for all studied elements. The consideration of the metal-organic matter binding through the NICA-Donnan model and Stockholm Humic Model for lead and copper, respectively, improves the former metal release prediction. Modelled curves can be useful for the environmental impact assessment of seawater acidification due to its match with the experimental values.This work was supported by the Spanish Ministry of Economy and Competitiveness, Project No. CTM 2011-28437-C02-01, ERDF included. M. C. Martı´n-Torre was funded by the Spanish Ministry of Economy and Competitiveness by means of FPI. Fellowship No. BES-2012-053816

Risk factors for self-harm in people with epilepsy

Objective:To estimate the risk of self-harm in people with epilepsy and identify factors which influence this risk.Methods: We identified people with incident epilepsy in the Clinical Practice Research Datalink (CPRD), linked to hospitalization and mortality data, in England (01/01/1998-03/31/2014). In Phase 1, we estimated risk of self-harm among people with epilepsy, versus those without, in a matched cohort study using a stratified-Cox proportional hazards model. In Phase 2, we delineated a nested case-control study from the incident epilepsy cohort. People who had self-harmed (cases) were matched with up to 20 controls. From conditional logistic regression models, we estimated relative risk of self-harm associated with mental and physical illness comorbidity, contact with healthcare services and antiepileptic drug (AED) use.Results: Phase 1 included 11,690 people with epilepsy and 215,569 individuals without. We observed an adjusted hazard ratio of 5.31 (95% CI 4.08-6.89) for self-harm in the first year following epilepsy diagnosis and 3.31 (95% CI 2.85-3.84) in subsequent years. In Phase 2, there were 273 cases and 3,790 controls. Elevated self-harm risk was associated with mental illness (OR 4.08, 95% CI 3.06-5.42), multiple General Practitioner consultations, treatment with two AEDs versus monotherapy (OR 1.84, 95% CI 1.33-2.55) and AED treatment augmentation (OR 2.12, 95% CI 1.38-3.26). Conclusion: People with epilepsy have elevated self-harm risk, especially in the first year following diagnosis. Clinicians should adequately monitor these individuals and be especially vigilant to self-harm risk in people with epilepsy and comorbid mental illness, frequent healthcare service contact, those taking multiple AEDs and during treatment augmentation

Search for Single-Top-Quark Production in p-pbar Collisions at sqrt(s)=1.8 TeV

We search for standard model single-top-quark production in the W-gluon fusion and W* channels using 106 pb^-1 of data from p-pbar collisions at sqrt(s)=1.8 TeV collected with the Collider Detector at Fermilab. We set an upper limit at 95% C.L. on the combined W-gluon fusion and W* single-top cross section of 14 pb, roughly six times larger than the standard model prediction. Separate 95% C.L. upper limits in the W-gluon fusion and W* channels are also determined and are found to be 13 and 18 pb, respectively.Comment: 6 pages, 2 figures; submitted to Phys. Rev. Let