Compromised CD8+ T cell immunity in the aged brain increases severity of neurotropic coronavirus infection and postinfectious cognitive impairment.

Advanced age increases the risk of severe disease from SARS-CoV-2 infection, as well as incidence of long COVID and SARS-CoV-2 reinfection. We hypothesized that perturbations in the aged antiviral CD8 T cell response predisposes elderly individuals to severe coronavirus infection, re-infection, and postinfectious cognitive sequelae. Using MHV-A59 as a murine model of respiratory coronavirus, we found that aging increased CNS infection and lethality to MHV infection.

Conserved allomorphs of MR1 drive the specificity of MR1-restricted TCRs.

Background: Major histocompatibility complex class-1-related protein (MR1), unlike human leukocyte antigen (HLA) class-1, was until recently considered to be monomorphic. MR1 presents metabolites in the context of host responses to bacterial infection. MR1-restricted TCRs specific to tumor cells have been described, raising interest in their potential therapeutic application for cancer treatment.

Orthopedic postoperative infection profile and antibiotic sensitivity of 2038 patients across 24 countries - Call for region and institution specific surgical antimicrobial prophylaxis.

Purpose: Improper utilization of surgical antimicrobial prophylaxis frequently leads to increased risks of morbidity and mortality.This study aims to understand the common causative organism of postoperative orthopedic infection and document the surgical antimicrobial prophylaxis protocol across various institutions in to order to strengthen surgical antimicrobial prophylaxis practice and provide higher-quality surgical care.

Methods: This multicentric multinational retrospective study, includes 24 countries from five different regions (Asia Pacific, South Eastern Africa, Western Africa, Latin America, and Middle East).

Circular External Fixator Removal in the Outpatient Clinic Using Regional Anaesthesia: A Pilot Study of a Novel Approach.

Introduction: External fixator (EF) devices are commonly used in the management of complex skeletal trauma, as well as in elective limb reconstruction surgery for the management of congenital and acquired pathology. The subsequent removal of an EF is commonly performed under general anaesthesia in an operating theatre. This practice is resource-intensive and limits the amount of time available for other surgical cases in the operating theatre.

Development, reliability, validity, and acceptability of the remote administration of the Edinburgh Cognitive and Behavioural ALS Screen (ECAS).

Background: ALS clinical care and research has changed dramatically since the COVID-19 pandemic, accelerating the need for cognitive assessments to be adapted for remote use.

Objectives: To develop the remote administration method of the Edinburgh Cognitive and Behavioural ALS Screen (ECAS), and determine its reliability and validity. Methods: The validation process consisted of: (1) Two versions of the ECAS (A and B) were administered, one in-person and one remotely via video call in a randomized order to 27 people without ALS; (2) The ECAS was administered remotely to 24 pwALS, with a second rater independently scoring performance; and (3) Acceptability was assessed by gathering feedback from 17 pwALS and 19 clinicians and researchers about their experience of using the ECAS remotely.

Optimizing CRE and PhiC31 mediated recombination in .

Genetic manipulation of is key to developing a deeper understanding of this insects' biology, vector-virus interactions and makes future genetic control strategies possible. Despite some advances, this process remains laborious and requires highly skilled researchers and specialist equipment. Here we present two improved methods for genetic manipulation in this species.

Decolonising food regulatory frameworks: importance of recognising traditional culture when assessing dietary safety of traditional foods.

As interest in Australian native products continues to grow worldwide, Aboriginal and Torres Strait Islander peoples (First Peoples) are striving to be industry leaders in the production of their traditional foods that are being developed for commercial markets. To successfully gain market approval both within Australia and globally, food regulatory authorities require at least a documented history of safe use to indicate dietary safety. Moreover, many countries also require compositional analysis and safety data to further support their safe human consumption.

Sternal fractures and thoracic injury: an analysis of 288 sternal fractures attending a major trauma centre.

Introduction: Sternal fractures (SF) are uncommon injuries usually associated with a significant mechanism of injury. Concomitant injury is likely, and a risk of mortality is substantial.

Aim: Our aim in this study was to identify the risk factors for mortality in patients who had sustained sternal fractures.

Enolate SAr of unactivated arenes [(η-arene)RuCp] intermediates.

A series of complexes of the general formula [(η-arene)RuCp][PF] (where arene = aryl halides or nitroarenes) were synthesised and the arene ring was found to be reactive towards an intermolecular nucleophilic aromatic substitution (SAr) reaction with a series of cyclic 1,3-diones. Competition experiments indicated that leaving group ability of the aryl halides and nitroarenes went in the order of F ≫ NO > Cl > Br. Following SAr, the arene rings were liberated quantitatively a rapid photolysis reaction (<15 min).

Perceptions of safety, subjective effects, and beliefs about the clinical utility of lysergic acid diethylamide in healthy participants within a novel intervention paradigm: Qualitative results from a proof-of-concept study.

Background: Classic psychedelics show promise in the treatment of mental health conditions; however, more scalable intervention protocols are needed to maximize access to these novel therapeutics. In this proof-of-concept study, perceptions of safety, subjective effects, and beliefs about the clinical utility of lysergic acid diethylamide (LSD) were evaluated among healthy participants ( = 31) administered 50 to 100 µg LSD in a treatment paradigm conceptualized as more scalable than traditional approaches to administering classic psychedelics.

Methods: Semi-structured interviews assessed participants' expectations, experience, and thoughts on the safety and efficacy of the study design.

Safety, tolerability, pharmacokinetics, and subjective effects of 50, 75, and 100 µg LSD in healthy participants within a novel intervention paradigm: A proof-of-concept study.

Background: Classic psychedelics hold promise as therapeutics for psychiatric disorders, but require scalable intervention protocols. This proof-of-concept study evaluated the safety, tolerability, pharmacokinetics, and subjective effects of 50, 75, and 100 µg lysergic acid diethylamide (LSD) in healthy adults within a novel intervention paradigm.

Methods: Up to three participants were administered LSD on the same day in separate rooms, each with a single attendant, after 1 day of preparation.

Clinical outcomes, Kadish-INSICA staging and therapeutic targeting of somatostatin receptor 2 in olfactory neuroblastoma.

Introduction: Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on a subset of our cohort to report on the potential efficacy of somatostatin receptor 2 (SSTR2)-targeting imaging and therapy.

Methods: We conducted a retrospective analysis of 404 primary, locally recurrent, and metastatic olfactory neuroblastoma (ONB) patients from 12 institutions in the United States of America, United Kingdom and Europe.

Novel ruthenium complexes bearing bipyridine-based and N-heterocyclic carbene-supported pyridine (NCN) ligands: the influence of ligands on catalytic transfer hydrogenation of ketones.

Transfer hydrogenation (TH) is a powerful synthetic tool in the production of secondary alcohols from ketones by using a non-H hydrogen source along with metal catalysts. Among homogeneous catalysts, Ru(II) complexes are the most efficient catalysts. In our research, six novel ruthenium(II) complexes bearing bipyridine-based ligands [Ru(L1)Cl] (1), [Ru(L1)(PPh)Cl]Cl (2) and [Ru(L2)Cl] (3) and N-heterocyclic carbene-supported pyridine (NCN) ligands [RuCp(L3)]PF (4), [RuCp*(L3)]PF (5), and [Ru(-cymene)(L3)Cl]PF (6) (where L1 = 6,6'-bis(aminomethyl)-2,2'-bipyridine, L2 = 6,6'-bis(dimethylaminomethyl)-2,2'-bipyridine and L3 = 1,3-bis(2-methylpyridyl)imidazolium bromide) were synthesised and characterised by NMR spectroscopy, HRMS, and X-ray crystallography.

Biological variation of cardiac myosin-binding protein C in healthy individuals.

Objectives: Cardiac myosin-binding protein C (cMyC) is a novel biomarker of myocardial injury, with a promising role in the triage and risk stratification of patients presenting with acute cardiac disease. In this study, we assess the weekly biological variation of cMyC, to examine its potential in monitoring chronic myocardial injury, and to suggest analytical quality specification for routine use of the test in clinical practice.

Methods: Thirty healthy volunteers were included.

Novel strategy for improved outcomes of extra-corporeal membrane oxygenation as a treatment for refractory post cardiotomy cardiogenic shock in the current era: a refreshing new perspective.

Objectives: Post-cardiotomy cardiogenic shock is an infrequent but important cause of death following cardiac surgery. Extra-corporeal membrane oxygenation offers the opportunity for temporary cardiovascular support and myocardial rest, with a view to recovery. We examine our results with our recently-implemented management algorithm.

Optimization of Benzothiazole and Thiazole Hydrazones as Inhibitors of Schistosome BCL-2.

Limited therapeutic options are available for the treatment of human schistosomiasis caused by the parasitic Schistosoma flatworm. The B cell lymphoma-2 (BCL-2)-regulated apoptotic cell death pathway in schistosomes was recently characterized and shown to share similarities with the intrinsic apoptosis pathway in humans. Here, we exploit structural differences in the human and schistosome BCL-2 (sBCL-2) pro-survival proteins toward a novel treatment strategy for schistosomiasis.

Synthesis of Biologically Active Heterospirocycles through Iterative 1,3-Dipolar Cycloaddition Pathways.

We demonstrate the novel spiroannulation of -imines with 1,3-dipoles, for the first time, leading to 3D spirocycles with a secondary amine (NH) in the spiro-ring. The synthetic method described herein allows access to these previously unexplored heterospirocyclic cores that have application in the discovery of functional molecules for medicinal and materials science. This was demonstrated by discovering an unprecedented class of heterospirocycles with antimalarial activity against the human protozoan .

As Nice as π: Aromatic Reactions Activated by π-Coordination to Transition Metals.

π-Coordination of aromatic molecules to metals dramatically alters their reactivity. For example, coordinated carbons become more electrophilic and C-H bonds of coordinated rings become more acidic. For many years, this change in reactivity has been used to trigger reactions that would not take place for uncoordinated arenes, however, there has been a recent resurgence in use of this technique, in part due to the development of catalytic reactions in which π-coordination is transient.

Correction to: The effects of microdose LSD on time perception: a randomised, double-blind, placebo-controlled trial.

The manufacturer of the drug product was Onyx Scientific Limited UK, to cGMP standards.

Uniportal subxiphoid bilateral removal of self-introduced thoracic foreign bodies.

This is a report of a 31-year-old male refugee, who was admitted to Intensive Therapy Unit after being found in severe chest pain after escaping extreme torture from his home country. He was found to have four nails in his thorax. These were removed using a subxiphoid video-assisted thorascopic surgery (VATS) technique.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of low dose lysergic acid diethylamide (LSD) in healthy older volunteers.

Unlabelled: Research has shown that psychedelics, such as lysergic acid diethylamide (LSD), have profound anti-inflammatory properties mediated by 5-HT receptor signaling, supporting their evaluation as a therapeutic for neuroinflammation associated with neurodegenerative disease.

Objective: This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of orally repeated administration of 5 μg, 10 μg, and 20 μg LSD in older healthy individuals. In the current paper, we present safety, tolerability, pharmacokinetics, and pharmacodynamic measures that relate to safety, tolerability, and dose response.

Neural correlates of the DMT experience assessed with multivariate EEG.

Studying transitions in and out of the altered state of consciousness caused by intravenous (IV) N,N-Dimethyltryptamine (DMT - a fast-acting tryptamine psychedelic) offers a safe and powerful means of advancing knowledge on the neurobiology of conscious states. Here we sought to investigate the effects of IV DMT on the power spectrum and signal diversity of human brain activity (6 female, 7 male) recorded via multivariate EEG, and plot relationships between subjective experience, brain activity and drug plasma concentrations across time. Compared with placebo, DMT markedly reduced oscillatory power in the alpha and beta bands and robustly increased spontaneous signal diversity.

Use of endoscopic vein harvesting (EVH) during coronary artery bypass grafting in United Kingdom: The EVH survey.

Objective: Endoscopic vein harvesting (EVH) is growing in popularity and is the method of choice in many centers worldwide as it is associated with lower complication rates compared to the open vein harvesting. The aim of this study was to determine the current use of EVH during coronary artery bypass grafting among cardiac surgeons in United Kingdom and identify the main concerns that limit the use of this technique.

Methods: We developed an online survey with 16 questions about the use of EVH.

Cardiac Myosin-Binding Protein C to Diagnose Acute Myocardial Infarction in the Pre-Hospital Setting.

Background Early triage is essential to improve outcomes in patients with suspected acute myocardial infarction (AMI). This study investigated whether cMyC (cardiac myosin-binding protein), a novel biomarker of myocardial necrosis, can aid early diagnosis of AMI and risk stratification. Methods and Results cMyC and high-sensitivity cardiac troponin T were retrospectively quantified in blood samples obtained by ambulance-based paramedics in a prospective, diagnostic cohort study.