Overexpression of adenosine A2A receptors in rats: effects on depression, locomotion, and anxiety

Adenosine A2A receptors (A2AR) are a sub-type of receptors enriched in basal ganglia, activated by the neuromodulator adenosine, which interact with dopamine D2 receptors. Although this reciprocal antagonistic interaction is well-established in motor function, the outcome in dopamine-related behaviors remains uncertain, in particular in depression and anxiety. We have demonstrated an upsurge of A2AR associated to aging and chronic stress. Furthermore, Alzheimer's disease patients present A2AR accumulation in cortical areas together with depressive signs. We now tested the impact of overexpressing A2AR in forebrain neurons on dopamine-related behavior, namely depression. Adult male rats overexpressing human A2AR under the control of CaMKII promoter [Tg(CaMKII-hA2AR)] and aged-matched wild-types (WT) of the same strain (Sprague-Dawley) were studied. The forced swimming test (FST), sucrose preference test (SPT), and the open-field test (OFT) were performed to evaluate behavioral despair, anhedonia, locomotion, and anxiety. Tg(CaMKII-hA2AR) animals spent more time floating and less time swimming in the FST and presented a decreased sucrose preference at 48 h in the SPT. They also covered higher distances in the OFT and spent more time in the central zone than the WT. The results indicate that Tg(CaMKII-hA2AR) rats exhibit depressive-like behavior, hyperlocomotion, and altered exploratory behavior. This A2AR overexpression may explain the depressive signs found in aging, chronic stress, and Alzheimer's disease

The use of a task through virtual reality in cerebral palsy using two different interaction devices (concrete and abstract) - a cross-sectional randomized study.

BACKGROUND: Cerebral Palsy (CP) is characterised by variable difficulties in muscular action, resulting in inability of the individual to perform functional movement. An option to provide functionality to the individual with CP is the use of computer innovation. The aim of this paper was to verify if there was any performance improvement in a task performed in a virtual environment and if there was transfer to the task performed in the real environment and vice versa in this population. METHODS: A computer program was developed comprising a motor task, but with two possibilities of user interaction: a) concrete interface (with physical contact): in which the individual touches the computer screen to finish the task and b) abstract interface (no physical contact): in which the individual performs a hand movement in front of the Kinect device. Participants were split into two groups. The experimental group consisted of 28 individuals with CP within the ages of 6 and 15 years old. The control group included 28 typically developing individuals mirroring the age and sex of the experimental group. RESULTS: Individuals from both groups were able to improve task performance and retain acquired information. The CP group presented worse performance than the control group in all phases of the study. Further findings showed that the CP group presented better performance in the abstract interface than in the concrete interface, whereas, in the control group, the opposite occurred: their best performance was in the concrete. CONCLUSIONS: Motor tasks performed by individuals with CP through an interface with a more virtual environment feature (abstract interface: Kinect) provided better performance when compared to an interface with a more real characteristic (concrete interface: Touchscreen). TRIAL REGISTRATION: ClinicalTrials.gov Identifier - NCT03352440; Date of registration - November 17, 2017

The IMPACT study: A clustered randomized controlled trial to assess the effect of a referral algorithm for axial spondyloarthritis

BACKGROUND: A substantial number of patients with chronic low back pain (CLBP) have axial spondyloarthritis (axSpA), but early recognition of these patients is difficult for general practitioners (GPs). The Case Finding Axial Spondyloarthritis (CaFaSpA) referral strategy has shown to be able to identify patients with CLBP at risk for axSpA, but its impact on clinical daily practice is yet unknown. OBJECTIVE: To assess the effect of the CaFaSpA referral strategy on pain caused by disability in primary care patients with CLBP. METHODS: Within this clustered randomized controlled trial 93 general practices were randomized to either the CaFaSpA referral model (intervention) or usual primary care (control). In each group primary care patients between 18 and 45 years with CLBP were included. The primary outcome was disability caused by CLBP, measured with the Roland Morris Disability Questionnaire (RMDQ) at baseline and four months. Secondary outcome was the frequency of new axSpA diagnosis. Descriptive analyses were performed, and a linear mixed-effects model was used. RESULTS: In total 679 CLBP patients were included of which 333 patients were allocated to the intervention group and 346 to the control group. Sixty-four percent were female and mean age was 36.2 years. The mean RMDQ score at baseline was 8.39 in the intervention group and 8.61 in the control group. At four months mean RMDQ score was 7.65 in the intervention group and 8.15 in the control group. This difference was not statistically significant (p = 0.50). Six (8%) out of the 75 finally referred patients, were diagnosed with axSpA by their rheumatologist. CONCLUSIONS: The CaFaSpA referral strategy for axSpA did not have an effect on disability after four months caused by CLBP. However, the strategy is able to detect the axSpA patient within the large CLBP population sufficiently. Trial registration number: NCT01944163, Clinicaltrials.gov

Age-related shift in LTD is dependent on neuronal adenosine A(2A) receptors interplay with mGluR5 and NMDA receptors

Synaptic dysfunction plays a central role in Alzheimer's disease (AD), since it drives the cognitive decline. An association between a polymorphism of the adenosine A2A receptor (A2AR) encoding gene-ADORA2A, and hippocampal volume in AD patients was recently described. In this study, we explore the synaptic function of A2AR in age-related conditions. We report, for the first time, a significant overexpression of A2AR in hippocampal neurons of aged humans, which is aggravated in AD patients. A similar profile of A2AR overexpression in rats was sufficient to drive age-like memory impairments in young animals and to uncover a hippocampal LTD-to-LTP shift. This was accompanied by increased NMDA receptor gating, dependent on mGluR5 and linked to enhanced Ca(2+) influx. We confirmed the same plasticity shift in memory-impaired aged rats and APP/PS1 mice modeling AD, which was rescued upon A2AR blockade. This A2AR/mGluR5/NMDAR interaction might prove a suitable alternative for regulating aberrant mGluR5/NMDAR signaling in AD without disrupting their constitutive activity

Search for Higgs bosons decaying to tautau pairs in ppbar collisions at sqrt(s) = 1.96 TeV

We present a search for the production of neutral Higgs bosons decaying into tautau pairs in ppbar collisions at a center-of-mass energy of 1.96 TeV. The data, corresponding to an integrated luminosity of 5.4 fb-1, were collected by the D0 experiment at the Fermilab Tevatron Collider. We set upper limits at the 95% C.L. on the product of production cross section and branching ratio for a scalar resonance decaying into tautau pairs, and we then interpret these limits as limits on the production of Higgs bosons in the minimal supersymmetric standard model (MSSM) and as constraints in the MSSM parameter space.Comment: 7 pages, 5 figures, submitted to PL

Measurement of the photon+b+b-jet production differential cross section in ppˉp\bar{p} collisions at \sqrt{s}=1.96~\TeV

We present measurements of the differential cross section dsigma/dpT_gamma for the inclusive production of a photon in association with a b-quark jet for photons with rapidities |y_gamma|< 1.0 and 30<pT_gamma <300 GeV, as well as for photons with 1.5<|y_gamma|< 2.5 and 30< pT_gamma <200 GeV, where pT_gamma is the photon transverse momentum. The b-quark jets are required to have pT>15 GeV and rapidity |y_jet| < 1.5. The results are based on data corresponding to an integrated luminosity of 8.7 fb^-1, recorded with the D0 detector at the Fermilab Tevatron $p\bar{p}$ Collider at sqrt(s)=1.96 TeV. The measured cross sections are compared with next-to-leading order perturbative QCD calculations using different sets of parton distribution functions as well as to predictions based on the kT-factorization QCD approach, and those from the Sherpa and Pythia Monte Carlo event generators.Comment: 10 pages, 9 figures, submitted to Phys. Lett.

Limits on anomalous trilinear gauge boson couplings from WW, WZ and Wgamma production in pp-bar collisions at sqrt{s}=1.96 TeV

We present final searches of the anomalous gammaWW and ZWW trilinear gauge boson couplings from WW and WZ production using lepton plus dijet final states and a combination with results from Wgamma, WW, and WZ production with leptonic final states. The analyzed data correspond to up to 8.6/fb of integrated luminosity collected by the D0 detector in pp-bar collisions at sqrt{s}=1.96 TeV. We set the most stringent limits at a hadron collider to date assuming two different relations between the anomalous coupling parameters Delta\kappa_\gamma, lambda, and Delta g_1^Z for a cutoff energy scale Lambda=2 TeV. The combined 68% C.L. limits are -0.057<Delta\kappa_\gamma<0.154, -0.015<lambda<0.028, and -0.008<Delta g_1^Z<0.054 for the LEP parameterization, and -0.007<Delta\kappa<0.081 and -0.017<lambda<0.028 for the equal couplings parameterization. We also present the most stringent limits of the W boson magnetic dipole and electric quadrupole moments.Comment: 10 pages, 5 figures, submitted to PL

Measurement of three-jet differential cross sections d sigma-3jet / d M-3jet in p anti-p collisions at sqrt(s)=1.96 TeV

We present the first measurement of the inclusive three-jet differential cross section as a function of the invariant mass of the three jets with the largest transverse momenta in an event in p anti-p collisions at sqrt(s) = 1.96 TeV. The measurement is made in different rapidity regions and for different jet transverse momentum requirements and is based on a data set corresponding to an integrated luminosity of 0.7 fb^{-1} collected with the D0 detector at the Fermilab Tevatron Collider. The results are used to test the three-jet matrix elements in perturbative QCD calculations at next-to-leading order in the strong coupling constant. The data allow discrimination between parametrizations of the parton distribution functions of the proton.Comment: 10 pages, 4 figures, 2 tables, submitted to Phys. Lett. B, corrected chi2 values for NNPD

Search for pair production of the scalar top quark in muon+tau final states

We present a search for the pair production of scalar top quarks ($\tilde{t}_{1}$), the lightest supersymmetric partners of the top quarks, in $p\bar{p}$ collisions at a center-of-mass energy of 1.96 TeV, using data corresponding to an integrated luminosity of {7.3 $fb^{-1}$} collected with the \dzero experiment at the Fermilab Tevatron Collider. Each scalar top quark is assumed to decay into a $b$ quark, a charged lepton, and a scalar neutrino ($\tilde{\nu}$). We investigate final states arising from $\tilde{t}_{1} \bar{\tilde{t}_{1}} \rightarrow b\bar{b}\mu\tau \tilde{\nu} \tilde{\nu}$ and $\tilde{t}_{1} \bar{\tilde{t}_{1}} \rightarrow b\bar{b}\tau\tau \tilde{\nu} \tilde{\nu}$. With no significant excess of events observed above the background expected from the standard model, we set exclusion limits on this production process in the ($m_{\tilde{t}_{1}}$,$m_{\tilde{\nu}}$) plane.Comment: Submitted to Phys. Lett.