Does warfarin prevent venous thromboembolic events in aPL-positive patients?

Yes, warfarin is effective in the secondary prevention of venous thromboembolic events (VTEs) for patients positive for lupus anticoagulant or anticardiolipin antibody (also known as antiphospholipid antibodies [aPL]) (strength of recommendation [SOR]: B, single cohort study, extrapolation from other RCTs). Patients should be treated for at least a year (SOR: C, consensus statement), and possibly indefinitely, with warfarin (SOR: B, small clinical trials and cohort studies). Moderate-intensity therapy (international normalized ratio [INR] range, 2.0-3.0) appears to be the best balance between risks and benefits (SOR: B, based on meta-analysis of 2 small randomized control trials

Investigation of the neural control of cough and cough suppression in humans using functional brain imaging

Excessive coughing is one of the mostcommonreasons for seeking medical advice, yet the available therapies for treating cough disorders are inadequate. Humans can voluntarily cough, choose to suppress their cough, and are acutely aware of an irritation that is present in their airways. This indicates a significant level of behavioral and conscious control over the basic cough reflex pathway. However, very little is known about the neural basis for higher brain regulation of coughing. The aim of the present study was to use functional brain imaging in healthy humans to describe the supramedullary control of cough and cough suppression. Our data show that the brain circuitry activated during coughing in response to capsaicin-evoked airways irritation is not simply a function of voluntarily initiated coughing and the perception of airways irritation. Rather, activations in several brain regions, including the posterior insula and posterior cingulate cortex, define the unique attributes of an evoked cough. Furthermore, the active suppression of irritant-evoked coughing is also associated with a unique pattern of brain activity, including an involvement of the anterior insula, anterior mid-cingulate cortex, and inferior frontal gyrus. These data demonstrate for the first time that evoked cough is not solely a brainstem-mediated reflex response to irritation of the airways, but rather requires active facilitation by cortical regions, and is further regulated by distinct higher order inhibitory processes. Copyright © 2011 the authors

A New DREADD Facilitates the Multiplexed Chemogenetic Interrogation of Behavior

DREADDs are chemogenetic tools widely used to remotely control cellular signaling, neuronal activity and behavior. Here we used a structure-based approach to develop a new Gi coupled DREADD using the kappa-opioid receptor as template (KORD) that is activated by the pharmacologically inert ligand salvinorin B (SALB). Activation of virally-expressed KORD in several neuronal contexts robustly attenuated neuronal activity and modified behaviors. Additionally, co-expression of the KORD and the Gq coupled M3-DREADD within the same neuronal population facilitated the sequential and bi-directional remote control of behavior. The availability of DREADDs activated by different ligands provides enhanced opportunities for investigating diverse physiological systems using multiplexed chemogenetic actuators

Representation of capsaicin-evoked urge-to-cough in the human brain using functional magnetic resonance imaging

Rationale: Coughing in humans is typically preceded by a desire (or urge) to cough. The neural circuitry involved in sensing airway irritation and generating the urge-to-cough in humans is essentially unknown. Objectives: The aim of the present study was to use functional brain imaging to describe the supramedullary regions that are activated in humans during capsaicin inhalation. Methods: Experiments were performed on 10 healthy subjects (5 males, 5 females). Capsaicin doses were individually tailored to evoke a transient and reversible urge-to-cough. Blood oxygen level–dependent (BOLD) functional magnetic resonance measures were collected during repeated 24-second challenges with capsaicin or saline inhalation and subjects were asked to rate the urge-to-cough intensity of each challenge. Measurements and Main Results: Capsaicin inhalation reliably evoked an urge-to-cough, which was associated with activations in a variety of brain regions, including the insula cortex, anterior midcingulate cortex, primary sensory cortex, orbitofrontal cortex, supplementary motor area, and cerebellum. Conclusions: These data provide the first insights into the cortical neuronal network involved in sensing airway irritation and modulating coughing in humans

Cipro e la memoria dell'antico fra Medioevo e Rinascimento. La percezione del passato romano dell'isola nel mondo occidentale

Cipro, crocevia di culture e culla di antiche civiltà, costituì nei secoli del Medioevo e del Rinascimento un baluardo dell'Occidente latino nello scacchiere del Mediterraneo orientale. Quale atteggiamento assunsero governanti e viaggiatori occidentali nei confronti del ricco passato classico dell'isola? Il libro affronta il tema secondo una prospettiva volutamente ampia, ricercando la nascita dell'archeologia e dell'epigrafia sul suolo cipriota, ripercorrendo le tappe della riscoperta dei testi classici relativi all'isola ed esaminando il rapporto sviluppatosi fra il XIII e il XVI secolo con i resti visibili dell'antico