Circulating large extracellular vesicles as diagnostic biomarkers of indeterminate thyroid nodules: multi-platform omics analysis.

Background: While most thyroid nodules are benign, 7-15% are malignant. Patients with indeterminate thyroid nodules (specifically Bethesda IV/Thy3f) often undergo diagnostic hemithyroidectomy to reach a diagnosis on final histology. The aim of this study was to assess the feasibility of circulating large extracellular vesicles as diagnostic biomarkers in patients presenting with Thy3f thyroid nodules.

Accelerated forgetting of a trauma-like event in healthy men and women after a single dose of hydrocortisone.

Posttraumatic stress disorder (PTSD) is characterised by dysregulated hypothalamic-pituitary-adrenal axis activity and altered glucocorticoid receptor sensitivity. Early treatment with glucocorticoids may reduce PTSD risk, although the effect of such treatment on the aetiologically critical step of traumatic-memory-formation remains unclear. Here we examine the effects of exogenous cortisol (hydrocortisone) in a preclinical model of PTSD, using a factorial (Drug × Sex), randomised-controlled, double-blind design.

Pharmacological modelling of dissociation and psychosis: an evaluation of the Clinician Administered Dissociative States Scale and Psychotomimetic States Inventory during nitrous oxide ('laughing gas')-induced anomalous states.

Rationale: A significant obstacle to an improved understanding of pathological dissociative and psychosis-like states is the lack of readily implemented pharmacological models of these experiences. Ketamine has dissociative and psychotomimetic effects but can be difficult to use outside of medical and clinical-research facilities. Alternatively, nitrous oxide (NO) - like ketamine, a dissociative anaesthetic and NMDAR antagonist - has numerous properties that make it an attractive alternative for modelling dissociation and psychosis.

Rewarding Subjective Effects of the NMDAR Antagonist Nitrous Oxide (Laughing Gas) Are Moderated by Impulsivity and Depressive Symptoms in Healthy Volunteers.

Background: Nitrous oxide (N2O) is an anesthetic gas with both therapeutic and abuse potential. Because N2O is an NMDA receptor (NMDAR) antagonist, its effects are expected to resemble those of the prototypical NMDAR antagonist, ketamine. In this study, we examined the subjective rewarding effects of N2O using measures previously employed in studies of ketamine.

Author Correction: Ketamine can reduce harmful drinking by pharmacologically rewriting drinking memories.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Ketamine can reduce harmful drinking by pharmacologically rewriting drinking memories.

Maladaptive reward memories (MRMs) are involved in the development and maintenance of acquired overconsumption disorders, such as harmful alcohol and drug use. The process of memory reconsolidation - where stored memories become briefly labile upon retrieval - may offer a means to disrupt MRMs and prevent relapse. However, reliable means for pharmacologically weakening MRMs in humans remain elusive.

An assessment of rapamycin for weakening binge-eating memories via reconsolidation: a pre-registered, double-blind randomised placebo-controlled experimental study.

Background: Maladaptive learning linking environmental food cues to high-palatability food reward plays a central role in overconsumption in obesity and binge eating disorders. The process of memory reconsolidation offers a mechanism to weaken such learning, potentially ameliorating over-eating behaviour. Here we investigated whether putatively interfering with synaptic plasticity using the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, could weaken retrieved chocolate reward memories through blockade of reconsolidation.

Reduction in the occurrence of distressing involuntary memories following propranolol or hydrocortisone in healthy women.

Background: Pharmacological treatments targeting the neuroendocrine stress response may hold special promise in secondary prevention of posttraumatic stress disorder (PTSD). However, findings from clinical trials have been inconsistent and the efficacy of specific drugs, their temporal window of efficacy, effective doses and the characteristics of likely treatment responders remain unclear.

Method: Using an experimental human model of distressing involuntary memory formation, we compare the effects of two drugs that have theoretical or empirical support as secondary preventive agents in PTSD.