Involuntary refreshing of mental representations.

Laboratory tasks have revealed that mental representations (e.g., mental imagery) can enter consciousness in a manner that is involuntary, reliable, and insuppressible. These effects illuminate the capacities of involuntary processes as well as the function of voluntary, conscious processing. The Reflexive Imagery Task was developed a decade ago to investigate these involuntary effects systematically. Can refreshing yield such involuntary effects? Refreshing is the reactivating in mind of a mental representation that was activated moments ago. It is associated with mental rehearsal and executive function. We investigated whether a mental representation (subvocalization of an object name) can arise in consciousness involuntarily after a delayed interval, when the relevant stimulus is no longer present, and in response to a cue. In Experiment 1, participants were instructed not to refresh a previously presented (6 s before) stimulus in response to a cue. Involuntary refreshing occurred on a substantive proportion (0.56) of the trials. Experiment 2 replicated and extended this finding (proportion of the trials = 0.53) with a refreshing task that was more challenging than that of Experiment 1. Our findings suggest that mental representations arising from processes such as refreshing can occur involuntarily. We discuss the theoretical implications of this conclusion.

Systematic Review of l-glutamine for Prevention of Vaso-occlusive Pain Crisis in Patients with Sickle Cell Disease.

l-glutamine was approved by the U.S. Food and Drug Administration (FDA) for sickle cell disease (SCD) in 2017. A vaso-occlusive crisis (VOC) occurs in persons with SCD and is associated with acute pain episodes. This systematic review summarizes the evidence for l-glutamine in the prevention of VOC and associated pain in patients with SCD. Medline, Embase, and International Pharmaceutical Abstracts were searched for records reporting on l-glutamine use in persons with SCD. Eligibility criteria identified primary reports of investigations conducted in humans who were administered l-glutamine, reported on outcomes related to VOC or associated pain, published in English, and were available as full text. All relevant efficacy, safety, participant demographic data, and study method characteristics were extracted and documented. Risk-of-bias assessments were conducted using the Risk of Bias in Non-Randomized Studies-of Interventions (ROBINS-I) tool and the revised Cochrane risk-of-bias tool for randomized studies. Three studies assessing the effect of exogenous l-glutamine administration in patients with SCD met eligibility criteria: one prospective nonrandomized controlled study and two prospective randomized controlled trials. Rate of VOC and related hospitalizations were reduced in patients receiving l-glutamine, although some conflicting results were noted between studies. l-glutamine was generally well tolerated. Limitations of one or more of the eligible studies included small sample size, nonblinding, and study groups that differed at baseline. l-glutamine has limited high-quality evidence supporting its use. Although l-glutamine is FDA approved for the prevention of frequent episodes of VOC pain, only one randomized controlled trial has strong evidence to support this indication. Based on the results of a systematic review, l-glutamine may be considered for patients unable to receive hydroxyurea or in addition to hydroxyurea for reduction in VOC and associated pain.

Zinc is a transmembrane agonist that induces platelet activation in a tyrosine phosphorylation-dependent manner.

Following platelet adhesion and primary activation at sites of vascular injury, secondary platelet activation is induced by soluble platelet agonists, such as ADP, ATP, thrombin and thromboxane. Zinc ions are also released from platelets and damaged cells and have been shown to act as a platelet agonist. However, the mechanism of zinc-induced platelet activation is not well understood. Here we show that exogenous zinc gains access to the platelet cytosol and induces full platelet aggregation that is dependent on platelet protein tyrosine phosphorylation, PKC and integrin αIIbß3 activity and is mediated by granule release and secondary signalling. ZnSO4 increased the binding affinity of GpVI, but not integrin α2ß1. Low concentrations of ZnSO4 potentiated platelet aggregation by collagen-related peptide (CRP-XL), thrombin and adrenaline. Chelation of intracellular zinc reduced platelet aggregation induced by a number of different agonists, inhibited zinc-induced tyrosine phosphorylation and inhibited platelet activation in whole blood under physiologically relevant flow conditions. Our data are consistent with a transmembrane signalling role for zinc in platelet activation during thrombus formation.