Orexin Receptor Antagonism, a New Sleep-Enabling Paradigm: A Proof-of-Concept Clinical Trial

Peer reviewe

Systematic review of dexketoprofen in acute and chronic pain

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: Dexketoprofen, an NSAID used in the management of acute and chronic pains, is licensed in several countries but has not previously been the subjected of a systematic review. We used published and unpublished information from randomised clinical trials (RCTs) of dexketoprofen in painful conditions to assess evidence on efficacy and harm. Methods: PubMed and Cochrane Central were searched for RCTs of dexketoprofen for pain of any aetiology. Reference lists of retrieved articles and reviews were also searched. Menarini Group produced copies of published and unpublished studies (clinical trial reports). Data were abstracted into a standard form. For studies reporting results of single dose administration, the number of patients with at least 50 % pain relief was derived and used to calculate the relative benefit (RB) and number-needed-to-treat (NNT) for one patient to achieve at least 50 % pain relief compared with placebo. Results: Thirty-five trials were found in acute pain and chronic pain; 6,380 patients were included, 3,381 receiving dexketoprofen. Information from 16 trials (almost half the total patients) wa

On-demand cell-autonomous gene therapy for brain circuit disorders

Several neurodevelopmental and neuropsychiatric disorders are characterized by intermittent episodes of pathological activity. Although genetic therapies offer the ability to modulate neuronal excitability, a limiting factor is that they do not discriminate between neurons involved in circuit pathologies and “healthy” surrounding or intermingled neurons. We describe a gene therapy strategy that down-regulates the excitability of overactive neurons in closed loop, which we tested in models of epilepsy. We used an immediate early gene promoter to drive the expression of Kv1.1 potassium channels specifically in hyperactive neurons, and only for as long as they exhibit abnormal activity. Neuronal excitability was reduced by seizure-related activity, leading to a persistent antiepileptic effect without interfering with normal behaviors. Activity-dependent gene therapy is a promising on-demand cell-autonomous treatment for brain circuit disorders

Influence of individual differences in the Behavioral Inhibition System and stimulus content (fear versus blood-disgust) on affective startle reflex modulation

Inconsistencies among affective startle reflex modulation studies may be due to differences in the startle potentiation produced by the specific content of the images used, to individual differences in sensitivity to negative stimuli, or to the interaction of both factors. To explore this interaction, 52 undergraduates obtaining extreme scores on a self-report measure of the Behavioral Inhibition System (BIS) participated in an affective startle reflex modulation paradigm. A significant interaction between BIS group (high versus low) and image content emerged from the MANOVA. Comparing startle magnitude between fear and pleasant images, low BIS participants did not seem to show startle potentiation, whereas high BIS participants did. Both groups displayed potentiated startle during blood-disgust images. The present results suggest the importance of considering personality variables and their interaction with image content in the affective startle modulation paradigm