The role of the psychedelic experience in psilocybin treatment for treatment-resistant depression.

Objective: To determine the relationships between psilocybin dose, psychedelic experiences, and therapeutic outcome in treatment-resistant depression.

Methods: For treatment-resistant depression, 233 participants received a single dose of 25, 10, or 1 mg of COMP360 psilocybin (a proprietary, pharmaceutical-grade synthesized psilocybin formulation, developed by the sponsor, Compass Pathfinder Ltd.) with psychological support.

MIBiG 4.0: advancing biosynthetic gene cluster curation through global collaboration.

Specialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015.

Diversity and structure of the deep-sea sponge microbiome in the equatorial Atlantic Ocean.

Sponges (phylum Porifera) harbour specific microbial communities that drive the ecology and evolution of the host. Understanding the structure and dynamics of these communities is emerging as a primary focus in marine microbial ecology research. Much of the work to date has focused on sponges from warm and shallow coastal waters, while sponges from the deep ocean remain less well studied.

Maramycin, a Cytotoxic Isoquinolinequinone Terpenoid Produced through Heterologous Expression of a Bifunctional Indole Prenyltransferase/Tryptophan Indole-Lyase in .

Isoquinolinequinones represent an important family of natural alkaloids with profound biological activities. Heterologous expression of a rare bifunctional indole prenyltransferase/tryptophan indole-lyase enzyme from P8-A2 in J1074 led to the activation of a putative isoquinolinequinone biosynthetic gene cluster and production of a novel isoquinolinequinone alkaloid, named maramycin (). The structure of maramycin was determined by analysis of spectroscopic (1D/2D NMR) and MS spectrometric data.

The smallest worthwhile effect on pain intensity of exercise therapy for people with chronic low back pain: a discrete choice experiment study.

To identify the smallest worthwhile effect (SWE) of exercise therapy for people with non-specific chronic low back pain (CLBP). Discrete choice experiment. The SWE was estimated as the lowest reduction in pain that participants would consider exercising worthwhile, compared to not exercising i.

Reporting of Observational Studies Explicitly Aiming to Emulate Randomized Trials: A Systematic Review.

Importance: Observational (nonexperimental) studies that aim to emulate a randomized trial (ie, the target trial) are increasingly informing medical and policy decision-making, but it is unclear how these studies are reported in the literature. Consistent reporting is essential for quality appraisal, evidence synthesis, and translation of evidence to policy and practice.

Objective: To assess the reporting of observational studies that explicitly aimed to emulate a target trial.

The smallest worthwhile effect on pain intensity of nonsteroidal anti-inflammatory drugs and exercise therapy for acute and chronic low back pain: a benefit-harm trade-off study.

Question: What are the smallest worthwhile effects of nonsteroidal anti-inflammatory drugs (NSAIDs) for people with acute and chronic low back pain (LBP)? What is the smallest worthwhile effect of individualised exercise for people with chronic LBP compared with no intervention?

Design: Benefit-harm trade-off study.

Participants: Participants were recruited by advertisement on social media and included if they were English-speaking adults in Australia who had non-specific LBP.

Outcome Measure: Pain intensity.

Movement behavior of swordfish provisions connectivity between the temperate and tropical southwest Pacific Ocean.

Swordfish (Xiphias gladius) are a widely distributed (45°N-45°S) large pelagic fish targeted by fisheries worldwide. Swordfish that occur at high latitudes tend to disproportionately be large adults, so their movements have implications for population dynamics and fisheries management. In the southwest Pacific, little is known about this subset of the stock and existing evidence suggests limited movement from the subtropics into cooler high latitude waters.

Psilocybin for treatment resistant depression in patients taking a concomitant SSRI medication.

Psilocybin is being investigated as a treatment in adults with treatment-resistant depression (TRD). Withdrawal from serotonergic antidepressant drugs is a common prerequisite for taking part in trials of psilocybin due to the possibility of ongoing antidepressant drugs altering the psychedelic effect. This phase II, exploratory, international, fixed-dose, open-label study explored the safety, tolerability, and efficacy of a synthetic form of psilocybin (investigational drug COMP360) adjunct to a selective serotonin reuptake inhibitor in participants with TRD.

Interrogation of an Enzyme Library Reveals the Catalytic Plasticity of Naturally Evolved [4+2] Cyclases.

Stereoselective carbon-carbon bond forming reactions are quintessential transformations in organic synthesis. One example is the Diels-Alder reaction, a [4+2] cycloaddition between a conjugated diene and a dienophile to form cyclohexenes. The development of biocatalysts for this reaction is paramount for unlocking sustainable routes to a plethora of important molecules.

The Efficacy of Graded Motor Imagery and Its Components on Phantom Limb Pain and Disability: A Systematic Review and Meta-Analysis.

Introduction: Graded Motor Imagery (GMI) is a non-invasive and inexpensive therapy used to treat Phantom Limb Pain (PLP) by sequentially activating motor networks in such a way that movement and pain are unpaired. The objective of this systematic review was to critically appraise relevant data on the efficacy of GMI and its components for reducing PLP and disability in amputees.

Methods: We searched 11 electronic databases for controlled trials investigating GMI and its components in amputees with PLP from inception until February 2023.

Discovery and biosynthetic assessment of ' sp. nov. isolated from a deep-sea sponge.

The deep sea is known to host novel bacteria with the potential to produce a diverse array of undiscovered natural products. Thus, understanding these bacteria is of broad interest in ecology and could also underpin applied drug discovery, specifically in the area of antimicrobials. Here, we isolate a new strain of from the tissue of the deep-sea sponge collected at a depth of 1869 m from the Gramberg Seamount in the Atlantic Ocean.

Correction: Back et al. A New Strain with Antibiotic Activity Isolated from the Microbiome of a Mid-Atlantic Deep-Sea Sponge. 2021, , 105.

After publication of this article [...

MIBiG 3.0: a community-driven effort to annotate experimentally validated biosynthetic gene clusters.

With an ever-increasing amount of (meta)genomic data being deposited in sequence databases, (meta)genome mining for natural product biosynthetic pathways occupies a critical role in the discovery of novel pharmaceutical drugs, crop protection agents and biomaterials. The genes that encode these pathways are often organised into biosynthetic gene clusters (BGCs). In 2015, we defined the Minimum Information about a Biosynthetic Gene cluster (MIBiG): a standardised data format that describes the minimally required information to uniquely characterise a BGC.

Rescaling pain intensity measures for meta-analyses of analgesic medicines for low back pain appears justified: an empirical examination from randomised trials.

Objective: Meta-analyses of analgesic medicines for low back pain often rescale measures of pain intensity to use mean difference (MD) instead of standardised mean difference for pooled estimates. Although this improves clinical interpretability, it is not clear whether this method is justified. Our study evaluated the justification for this method.

The effects of psilocybin on cognitive and emotional functions in healthy participants: Results from a phase 1, randomised, placebo-controlled trial involving simultaneous psilocybin administration and preparation.

Background: Psilocybin, a psychoactive serotonin receptor partial agonist, has been reported to acutely reduce clinical symptoms of depressive disorders. Psilocybin's effects on cognitive function have not been widely or systematically studied.

Aim: The aim of this study was to explore the safety of simultaneous administration of psilocybin to healthy participants in the largest randomised controlled trial of psilocybin to date.

Rare presentation of Fabry disease as 'burnt-out' hypertrophic cardiomyopathy.

We herein report the case of a 53-year-old man who was historically diagnosed with hypertrophic cardiomyopathy (HCM) and was lost to follow-up, before presenting with end-stage heart failure. This was initially suspected as dilated cardiomyopathy and then 'burnt-out phase' of HCM but subsequently the underlying diagnosis was Fabry disease. Fabry disease is an uncommon lysosomal-storage disease due to reduced or absent activity of the alpha-galactosidase A enzyme.

Leibovich score is the optimal clinico-pathological system associated with recurrence of non-metastatic clear cell renal cell carcinoma.

Purpose: To determine the optimal post-operative risk stratification system associated with survival following surgery for clear cell renal cell carcinoma (ccRCC): tumour grade, tumour stage, Leibovich 2003, Leibovich 2018, Kattan, Stage, size, grade and necrosis (SSIGN) or UCLA Integrated Staging System (UISS) scores.

Methods: 542 patients with non-metastatic ccRCC who underwent nephrectomy 2008-2018 were reviewed. Primary outcome was recurrence-free survival (RFS), with secondary outcomes cancer-specific survival (CSS) and overall survival (OS).

A New Strain with Antibiotic Activity Isolated from the Microbiome of a Mid-Atlantic Deep-Sea Sponge.

To tackle the growing problem of antibiotic resistance, it is essential to identify new bioactive compounds that are effective against resistant microbes and safe to use. Natural products and their derivatives are, and will continue to be, an important source of these molecules. Sea sponges harbour a diverse microbiome that co-exists with the sponge, and these bacterial communities produce a rich array of bioactive metabolites for protection and resource competition.

The Bristol Sponge Microbiome Collection: A Unique Repository of Deep-Sea Microorganisms and Associated Natural Products.

The deep ocean is the largest habitat for life on Earth, though the microorganisms that occupy this unique environmental niche remain largely unexplored. Due to the significant logistical and operational challenges associated with accessing the deep ocean, bioprospecting programmes that seek to generate novel products from marine organisms have, to date, focused predominantly on samples recovered from shallow seas. For this reason, the deep ocean remains a largely untapped resource of novel microbiological life and associated natural products.

Acute Kidney Injury in Primary Care: A Review of Patient Follow-Up, Mortality, and Hospital Admissions following the Introduction of an AKI Alert System.

Background/aims: In February 2017, our laboratory implemented an electronic AKI flagging system for primary care using the NHS England AKI detection algorithm. Our study investigated the impact on patient follow-up, hospital admission, length of stay, and mortality.

Methods: Primary care results March 2017-February 2018 with an AKI test code were downloaded from the pathology computer.

Long-term outcomes in elderly patients with ANCA-associated vasculitis.

Objective: ANCA-associated vasculitis (AAV) is a small vessel vasculitis that commonly presents in the elderly. However, there are few long-term outcome data for these patients. Here, we assessed long-term outcomes in a single-centre cohort of elderly patients with AAV.