Cooperative Glutamatergic and Cholinergic Mechanisms Generate Short-Term Modifications of Synaptic Effectiveness in Prepositus Hypoglossi Neurons

To maintain horizontal eye position on a visual target after a saccade, extraocular motoneurons need a persistent (tonic) neural activity, called "eye-position signal," generated by prepositus hypoglossi (PH) neurons. We have shown previously in vitro and in vivo that this neural activity depends, among others mechanisms, on the interplay of glutamatergic transmission and cholinergic synaptically triggered depolarization. Here, we used rat sagittal brainstem slices, including PH nucleus and paramedian pontine reticular formation (PPRF). We made intracellular recordings of PH neurons and studied their synaptic activation from PPRF neurons. Train stimulation of the PPRF area evoked a cholinergic-sustained depolarization of PH neurons that outlasted the stimulus. EPSPs evoked in PH neurons by single pulses applied to the PPRF presented a short-term potentiation (STP) after train stimulation. APV (an NMDA-receptor blocker) or chelerythrine (a protein kinase-C inhibitor) had no effect on the sustained depolarization, but they did block the evoked STP, whereas pirenzepine (an M1 muscarinic antagonist) blocked both the sustained depolarization and the STP of PH neurons. Thus, electrical stimulation of the PPRF area activates both glutamatergic and cholinergic axons terminating in the PH nucleus, the latter producing a sustained depolarization probably involved in the genesis of the persistent neural activity required for eye fixation. M1-receptor activation seems to evoke a STP of PH neurons via NMDA receptors. Such STP could be needed for the stabilization of the neural network involved in the generation of position signals necessary for eye fixation after a saccade

Production of vector resonances at the LHC via WZ-scattering: a unitarized EChL analysis

In the present work we study the production of vector resonances at the LHC by means of the vector boson scattering $WZ \to WZ$ and explore the sensitivities to these resonances for the expected future LHC luminosities. We are assuming that these vector resonances are generated dynamically from the self interactions of the longitudinal gauge bosons, $W_L$ and $Z_L$, and work under the framework of the electroweak chiral Lagrangian to describe in a model independent way the supposedly strong dynamics of these modes. The properties of the vector resonances, mass, width and couplings to the $W$ and $Z$ gauge bosons are derived from the inverse amplitude method approach. We implement all these features into a single model, the IAM-MC, adapted for MonteCarlo, built in a Lagrangian language in terms of the electroweak chiral Lagrangian and a chiral Lagrangian for the vector resonances, which mimics the resonant behavior of the IAM and provides unitary amplitudes. The model has been implemented in MadGraph, allowing us to perform a realistic study of the signal versus background events at the LHC. In particular, we have focused our study on the $pp\to WZjj$ type of events, discussing first on the potential of the hadronic and semileptonic channels of the final $WZ$, and next exploring in more detail the clearest signals. These are provided by the leptonic decays of the gauge bosons, leading to a final state with $\ell_1^+\ell_1^-\ell_2^+\nu jj$, $\ell=e,\mu$, having a very distinctive signature, and showing clearly the emergence of the resonances with masses in the range of 1.5-2.5 TeV, which we have explored.Comment: Revised version accepted for publication in JHEP. Enlarged analysis. References added. 44 pages, 23 figures, 3 table

A Cholinergic Synaptically Triggered Event Participates in the Generation of Persistent Activity Necessary for Eye Fixation

An exciting topic regarding integrative properties of the nervous system is how transient motor commands or brief sensory stimuli are able to evoke persistent neuronal changes, mainly as a sustained, tonic action potential firing. A persisting firing seems to be necessary for postural maintenance after a previous movement. We have studied in vitro and in vivo the generation of the persistent neuronal activity responsible for eye fixation after spontaneous eye movements. Rat sagittal brainstem slices were used for the intracellular recording of prepositus hypoglossi (PH) neurons and their synaptic activation from nearby paramedian pontine reticular formation (PPRF) neurons. Single electrical pulses applied to the PPRF showed a monosynaptic glutamatergic projection on PH neurons, acting on AMPA-kainate receptors. Train stimulation of the PPRF area evoked a sustained depolarization of PH neurons exceeding (by hundreds of milliseconds) stimulus duration. Both duration and amplitude of this sustained depolarization were linearly related to train frequency. The train-evoked sustained depolarization was the result of interaction between glutamatergic excitatory burst neurons and cholinergic mesopontine reticular fibers projecting onto PH neurons, because it was prevented by slice superfusion with cholinergic antagonists and mimicked by cholinergic agonists. As expected, microinjections of cholinergic antagonists in the PH nucleus of alert behaving cats evoked a gaze-holding deficit consisting of a re-centering drift of the eye after each saccade. These findings suggest that a slow, cholinergic, synaptically triggered event participates in the generation of persistent activity characteristic of PH neurons carrying eye position signals

Phenomenology of a lepton triplet

The most general phenomenological model involving a lepton triplet with hypercharge $\pm 1$ is constructed. A distinctive feature of this model is the prediction of a doubly charged lepton, and a new heavy Dirac neutrino. We study the phenomenology of these exotic leptons in both low-energy experiments and at the LHC. The model predicts FCNC processes such as rare muon decays, which are studied in detail in order to constrain the model parameters. All the decay channels of the exotic leptons are described for a wide range of parameters. It is found that, if the mixing parameters between the exotic and light leptons are not too small ($>10^{-6}$), then they can be observable to a $3-5\sigma$ statistical significance at the 7 TeV LHC with 10-50 fb$^{-1}$ luminosity for a 400 GeV mass, and 14 TeV with 100-300 fb$^{-1}$ luminosity for a 800 GeV mass.Comment: 28 pages, 17 figures. Version to appear in PR

Prevalence and predictors of inadequate patient medication knowledge

© 2016 John Wiley & Sons, Ltd. Objectives: To assess medication knowledge in adult patients and to explore its determinants. Method: Cross-sectional study. Medication knowledge was the primary outcome and was assessed using a previously validated questionnaire. A multivariate logistic regression analysis was performed to explore the association between medication knowledge and the factors included in the model. Results: Seven thousand two hundred seventy-eight patients participated in the study. 71.9% (n = 5234) (95% CI: 70.9%–73.0%) of the surveyed patients had an inadequate knowledge of the medication they were taking. The dimensions obtaining the highest level of knowledge were the ‘medication use process’ and ‘therapeutic objective of medication’. The items ‘frequency’ (75.4%), ‘dosage’ (74.5%) and ‘indication’ (70.5%) had the highest percentage of knowledge. Conversely, ‘medication safety’ represented the dimension with the lowest scores, ranging from 12.6% in the item “contraindications” to 15.3% in the item ‘side effects’. The odds ratio (OR) of having an inadequate medication knowledge increased for unskilled workers (OR: 1.33; 85% CI:1.00–1.78; P = 0.050), caregivers (OR:1.46; 95% CI:1.18–1.81; P < 0.001), patients using more than one medication (OR: 1.14; 95% CI: 1.00–1.31; P = 0.050) and patients who did not know the name of the medication they were taking (OR: 2.14, 95% CI: 1.71–2.68 P < 0.001). Conclusion: Nearly three quarters of the analysed patients had inadequate knowledge regarding the medicines they were taking. Unskilled workers and caregivers were at a higher risk of lacking of medication knowledge. Other factors that correlated with inadequate medication knowledge were the use of more than one drug and not knowing the name of the medication dispensed