Efficacy of GABA aminotransferase inactivator OV329 in models of neuropathic and inflammatory pain without tolerance or addiction.

Dysregulation of GABAergic inhibition is associated with pathological pain. Consequently, enhancement of GABAergic transmission represents a potential analgesic strategy. However, therapeutic potential of current GABA agonists and modulators is limited by unwanted side effects.

Emergency and postoperative access to critical and enhanced care: a multicentre prospective observational study.

Introduction: The ability to admit patients to enhanced or critical care may be limited by bed availability. In a network with low provision of critical and enhanced care beds, we aimed to assess the proportion of patients having surgery with moderate (1%-< 5%) or high (≥ 5%) predicted risk of 30-day postoperative mortality and their postoperative care location. We also aimed to study referral and admission outcomes to critical care.

Palmitoylethanolamide causes dose-dependent changes in brain function and the lipidome.

The present studies were undertaken to understand the effects of the commonly used nutraceutical PEA on brain function and lipid chemistry. These studies using MRI and broad-scale lipidomics are without precedent in animal or human research. During the MRI scanning session awake rats were given one of three doses of PEA (3, 10, or 30 mg/kg) or vehicle and imaged for changes in BOLD signal and functional connectivity.

Visual exposure to green light therapy reduces knee joint pain and alters the lipidome in osteoarthritic rats.

Visual exposure to dim, green, light has been found to reduce pain levels in patients living with migraine, low back pain, and fibromyalgia. Preclinical studies discovered that the analgesic effect of green light was due to the central release of endogenous opioids and a reduction in inflammatory cytokines in the cerebrospinal fluid. The present study assessed the effect of green light therapy (GLT) on joint pain in a rat model of osteoarthritis (OA) and investigated the role of endolipids.

Genetic deletion of NAPE-PLD induces context-dependent dysregulation of anxiety-like behaviors, stress responsiveness, and HPA-axis functionality in mice.

Unlabelled: The endocannabinoid (eCB) system regulates stress responsiveness and hypothalamic-pituitary-adrenal (HPA) axis activity. The enzyme -acyl phosphatidylethanolamine phospholipase-D (NAPE-PLD) is primarily responsible for the synthesis of the endocannabinoid signaling molecule anandamide (AEA) and other structurally related lipid signaling molecules known as -acylethanolamines (NAEs). However, little is known about how activity of this enzyme affects behavior.

Hypoactivation of the language network during auditory imagery contributes to hallucinations in Schizophrenia.

Auditory verbal hallucinations (AVHs) involve perceptions, often voices, in the absence of external stimuli, and rank among the most common symptoms of schizophrenia. Metrical stress evaluation requires determination of the stronger syllable in words, and therefore requires auditory imagery, of interest for investigation of hallucinations in schizophrenia. The current functional magnetic resonance imaging study provides an updated whole-brain network analysis of a previously published study on metrical stress, which showed reduced directed connections between Broca's and Wernicke's regions of interest (ROIs) for hallucinations.

Soundless voices, silenced selves: are auditory verbal hallucinations in schizophrenia truly perceptual?

In much contemporary psychiatric training and practice, there is a strong emphasis on the audible or perceptual quality and externality of auditory verbal hallucinations in clinical assessments. A typical question during clinical assessment is asking whether the voices that a person hears sound identical to the way the clinician's voice is heard. In this Personal View, we argue that the most important factor in auditory verbal hallucinations in schizophrenia spectrum psychoses is a loss of first-person authority, and that a perceptual quality is not required for it to be this kind of hallucination.

Dimensions of beliefs without strong supporting evidence and reasons for holding them.

Beliefs without strong supporting evidence (BWSSE) are commonplace, such as religious beliefs and conspiracy theories. The goals of the current study were to identify dimensions of BWSSE in the general public and study how reasons for holding each dimension depend on the strength of the belief. Participants completed a BWSSE questionnaire online, and principal component analysis suggested that the questionnaire captured 6 dimensions of beliefs that range in strength: New Age Spiritual, Traditional Spiritual, Nonconformist, Science, Mythical, and Conspiracy Theory.

20 Factors influencing the discard of clinical tissue and NHSBT methods to maintain a low discard rate.

Introduction: NHS Blood and Transplant Tissue and Eye Services (TES) is a human multi-tissue, tissue bank supplying tissue for transplant to surgeons throughout the UK. NHSBT has two Eye Banks. These are NHSBT Filton, based in Bristol and NHSBT David Lucas Eye Bank, which is based in Speke Liverpool.

Quality-adjusted time without symptoms of disease or toxicity and quality-adjusted progression-free survival with niraparib maintenance in first-line ovarian cancer in the PRIMA trial.

Background: The PRIMA phase 3 trial showed niraparib significantly prolongs median progression-free survival (PFS) placebo in patients with advanced ovarian cancer (OC) responsive to first-line platinum-based chemotherapy, including those who had tumors with homologous recombination deficiency (HRd). This analysis of PRIMA examined the quality-adjusted PFS (QA-PFS) and quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) of patients on maintenance niraparib placebo.

Methods: Patients were randomized 2:1 to receive once-daily maintenance niraparib ( = 487) or placebo ( = 246).

Altered activity in functional brain networks involved in lexical decision making in bipolar disorder: An fMRI case-control study.

Background: Brain networks involved in language, attentional and response processes are detectable by fMRI during lexical decision (LD). Here, we investigated possible abnormalities in the functional networks involved in LD in patients with bipolar disorder (BD).

Methods: fMRI and behavioural data were compared between BD (n = 25) and control (n = 21), with groups matched for age and sex.

Real-Time Symptom Capture of Hallucinations in Schizophrenia with fMRI: Absence of Duration-Dependent Activity.

Background: While advances in the field of functional magnetic resonance imaging (fMRI) provide new opportunities to study brain networks underlying the experience of hallucinations in psychosis, there are methodological challenges unique to symptom-capture studies.

Study Design: We extracted brain networks activated during hallucination-capture for schizophrenia patients when fMRI data collected from two sites was merged (combined = 27). A multidimensional analysis technique was applied, which would allow separation of brain networks involved in the hallucinatory experience itself from those involved in the motor response of indicating the beginning and end of the perceived hallucinatory experience.

Impact of disease progression on health-related quality of life of advanced ovarian cancer patients - Pooled analysis from the PRIMA trial.

Objective: Progression-free survival (PFS) is an important early efficacy endpoint in ovarian cancer (OC) and its relevance to patients should be assessed. PRIMA, a phase III trial, assessed niraparib in patients with OC; this post hoc analysis examined the relationship between disease progression in OC and health-related quality of life (HRQoL).

Methods: The PRIMA trial randomized patients with advanced OC responsive to first-line platinum-based chemotherapy to once daily maintenance oral niraparib or placebo.

Group therapy for schizophrenia: Why Burlingame et al. (2020) should redo their meta-analysis.

Comments on the meta-analysis by G. M. Burlingame et al.

Functional brain networks underlying probabilistic reasoning and delusions in schizophrenia.

Delusions in schizophrenia are false beliefs that are assigned certainty and not afforded the scrutiny that normally gives rise to doubt, even under conditions of weak evidence. The goal of the current functional magnetic resonance imaging (fMRI) study is to identify the brain network(s) involved in gathering information under conditions of weak evidence, in people with schizophrenia experiencing delusions. fMRI activity during probabilistic reasoning in people with schizophrenia experiencing delusions (n = 29) compared to people with schizophrenia not experiencing delusions (n = 41) and healthy controls (n = 41) was observed when participants made judgments based on evidence that weakly or strongly matched (or mismatched) with the focal hypothesis.

Metacognitive training for psychosis (MCT): past, present, and future.

This article provides an overview and retrospective on metacognitive training for psychosis (MCT), which first appeared approximately 2 decades ago. We recount how our empirical understanding of psychosis at that time led to the first preliminary version of the program. We describe setbacks and challenges that led to major changes, including revisions to existing modules (e.

Comprehensive Mutational Analysis of the Lasso Peptide Klebsidin.

Antibiotic resistance is a growing threat to public health, making the development of antibiotics of critical importance. One promising class of potential new antibiotics are ribosomally synthesized and post-translationally modified peptides (RiPPs), which include klebsidin, a lasso peptide from that inhibits certain bacterial RNA polymerases. We develop a high-throughput assay based on growth inhibition of to analyze the mutational tolerance of klebsidin.

Remote cognitive assessment in severe mental illness: a scoping review.

Many individuals living with severe mental illness, such as schizophrenia, present cognitive deficits and reasoning biases negatively impacting clinical and functional trajectories. Remote cognitive assessment presents many opportunities for advancing research and treatment but has yet to be widely used in psychiatric populations. We conducted a scoping review of remote cognitive assessment in severe mental illness to provide an overview of available measures and guide best practices.

Remote group therapies for cognitive health in schizophrenia-spectrum disorders: Feasible, acceptable, engaging.

Severe cognitive impairments and cognitive distortions are core to schizophrenia-spectrum disorders (SSDs) and are associated with deteriorated social functioning. Despite well-established efficacy of group psychosocial therapies targeting cognitive health in SSDs, dissemination of these programs remains limited. Remote delivery offers a promising strategy for increasing the programs' accessibility.

Endoscopic Management of Luminal Strictures: Beyond Dilation.

Luminal strictures can occur as part of many different gastrointestinal (GI) disorders anywhere along the GI tract and affect all age groups. The end goal of managing any stricture is to re-establish an adequate and durable luminal patency that is sufficient to resolve the presenting clinical symptoms. Treatment options can be generally categorized into medical, endoscopic, and surgical.

A limited access oral oxycodone paradigm produces physical dependence and mesocorticolimbic region-dependent increases in DeltaFosB expression without preference.

The abuse of oral formulations of prescription opioids has precipitated the current opioid epidemic. We developed an oral oxycodone consumption model consisting of a limited access (4 h) two-bottle choice drinking in the dark (TBC-DID) paradigm and quantified dependence with naloxone challenge using mice of both sexes. We also assessed neurobiological correlates of withdrawal and dependence elicited via oral oxycodone consumption using immunohistochemistry for DeltaFosB (ΔFosB), a transcription factor described as a molecular marker for drug addiction.

Selective targeting of NaV1.7 via inhibition of the CRMP2-Ubc9 interaction reduces pain in rodents.

The voltage-gated sodium NaV1.7 channel, critical for sensing pain, has been actively targeted by drug developers; however, there are currently no effective and safe therapies targeting NaV1.7.