Ischemic Stroke Prevention in Patients Atrial Fibrillation and a Recent Ischemic Stroke, TIA, or Intracranial Hemorrhage; a World Stroke Organisation (WSO) Scientific Statement.

Background: Secondary stroke prevention in patients with atrial fibrillation (AF) is one of the fastest growing areas in the field of cerebrovascular diseases. This Scientific statement from the World Stroke Organization Brain & Heart Task Force provides a critical analysis of the strength of current evidence this topic, highlights areas of current controversy, identifies knowledge gaps, and proposes priorities for future research.

Methods: We select topics with the highest clinical relevance and perform a systematic search to answer specific practical questions.

Thanatin and vinyl sulfide analogues as narrow spectrum antimicrobial peptides that synergise with polymyxin B.

Thanatin is a β-hairpin antimicrobial peptide cyclised by a single disulfide bond that has shown potent broad-spectrum activity towards bacterial and fungal pathogens. Towards Gram-negative species, thanatin acts both by forming trans-membranal pores and inhibiting outer membrane biogenesis by binding to LptA and blocking lipopolysaccharide (LPS) transport. Inspired by previous modifications of thanatin, an analogue was prepared which demonstrated potent but selective activity towards .

Impact of European Stroke Organisation secondary prevention guideline for ischaemic stroke / transient ischaemic attack.

Objectives: We aimed to assess secondary prevention strategies after ischaemic stroke or transient ischaemic attack (TIA).

Materials And Methods: We investigated the impact of European Stroke Organisation (ESO) Guideline recommendations for secondary prevention on recurrent events among people with non-cardioembolic ischaemic stroke or TIA. We assessed the following interventions by survival analysis or modelling impacts from clinical trial data: two blood pressure (BP) drugs compared to one drug; LDL-cholesterol target <1.

The Antimicrobial Peptide Capitellacin: Chemical Synthesis of Analogues to Probe the Role of Disulphide Bridges and Their Replacement with Vinyl Sulphides.

Capitellacin () is a 20-residue antimicrobial β-hairpin, produced by the marine polychaeta (segmented worms) . Since its discovery in 2020, only very limited studies have been undertaken to understand capitellacin's structure-activity relationship (SAR). Using fast-flow Fmoc-SPPS, a focused library of capitellacin analogues was prepared to systematically study the influence of the two disulphide bridges on its structure and activity, and their replacement with a vinyl sulphide as a potential bioisostere.

Natriuretic Peptides to Classify Risk of Atrial Fibrillation Detection After Stroke: Analysis of the BIOSIGNAL and PRECISE Cohort Studies.

Background And Objectives: Prolonged cardiac monitoring (PCM) increases atrial fibrillation (AF) detection after ischemic stroke, but access is limited, and it is burdensome for patients. Our objective was to assess whether midregional proatrial natriuretic peptide (MR-proANP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) could classify people who are unlikely to have AF after ischemic stroke and allow better targeting of PCM.

Methods: We analyzed people from the Biomarker Signature of Stroke Aetiology (BIOSIGNAL) study with ischemic stroke, no known AF, and ≥3 days cardiac monitoring.

Allenamides as a Powerful Tool to Incorporate Diversity: Thia-Michael Lipidation of Semisynthetic Peptides and Access to β-Keto Amides.

Lipopeptides are an important class of biomolecules for drug development. Compared with conventional acylation, a chemoselective lipidation strategy offers a more efficient strategy for late-stage structural derivatisation of a peptide scaffold. It provides access to chemically diverse compounds possessing intriguing and non-native moieties.

Allopurinol and blood pressure variability following ischemic stroke and transient ischemic attack: a secondary analysis of XILO-FIST.

Blood Pressure Variability (BPV) is associated with cardiovascular risk and serum uric acid level. We investigated whether BPV was lowered by allopurinol and whether it was related to neuroimaging markers of cerebral small vessel disease (CSVD) and cognition. We used data from a randomised, double-blind, placebo-controlled trial of two years allopurinol treatment after recent ischemic stroke or transient ischemic attack.

Synthesis, Structure-Activity Relationship Study, Bioactivity, and Nephrotoxicity Evaluation of the Proposed Structure of the Cyclic Lipodepsipeptide Brevicidine B.

The brevicidines represent a novel class of nonribosomal antimicrobial peptides that possess remarkable potency and selectivity toward highly problematic and resistant Gram-negative pathogenic bacteria. A recently discovered member of the brevicidine family, coined brevicidine B (), comprises a single amino acid substitution (from d-Tyr to d-Phe) in the amino acid sequence of the linear moiety of brevicidine () and was reported to exhibit broader antimicrobial activity against both Gram-negative (MIC = 2-4 μgmL) and Gram-positive (MIC = 2-8 μgmL) pathogens. Encouraged by this, we herein report the first total synthesis of the proposed structure of brevicidine B (), building on our previously reported synthetic strategy to access brevicidine ().

A Portable and Disposable Electrochemical Sensor Utilizing Laser-Scribed Graphene for Rapid SARS-CoV-2 Detection.

The COVID-19 pandemic caused by the virus SARS-CoV-2 was the greatest global threat to human health in the last three years. The most widely used methodologies for the diagnosis of COVID-19 are quantitative reverse transcription polymerase chain reaction (RT-qPCR) and rapid antigen tests (RATs). PCR is time-consuming and requires specialized instrumentation operated by skilled personnel.

Polymyxin B and ethylenediaminetetraacetic acid act synergistically against and .

Polymyxin B and ethylenediaminetetraacetic acid are antimicrobials possessing antibiofilm activity. They act by displacement and chelation, respectively, of divalent cations in bacterial membranes and may therefore act synergistically when applied in combination. If so, this combination of agents may be useful for the treatment of diseases like cystic fibrosis (CF), in which biofilms are present on the respiratory epithelium.

Antimicrobial Peptides Incorporating Halogenated Marine-Derived Amino Acid Substituents.

Small synthetic mimics of cationic antimicrobial peptides represent a promising class of compounds with leads in clinical development for the treatment of persistent microbial infections. The activity and selectivity of these compounds rely on a balance between hydrophobic and cationic components, and here, we explore the activity of 19 linear cationic tripeptides against five different pathogenic bacteria and fungi, including clinical isolates. The compounds incorporated modified hydrophobic amino acids inspired by motifs often found in bioactive marine secondary metabolites in combination with different cationic residues to probe the possibility of generating active compounds with improved safety profiles.

European Stroke Organisation (ESO) expedited recommendation on tenecteplase for acute ischaemic stroke.

Within the last year, four randomised-controlled clinical trials (RCTs) have been published comparing intravenous thrombolysis (IVT) with tenecteplase and alteplase in acute ischaemic stroke (AIS) patients with a non-inferiority design for three of them. An expedited recommendation process was initiated by the European Stroke Organisation (ESO) and conducted according to ESO standard operating procedure based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. We identified three relevant Population, Intervention, Comparator, Outcome (PICO) questions, performed systematic reviews of the literature and meta-analyses, assessed the quality of the available evidence, and wrote evidence-based recommendations.

Molecular biomarkers predicting newly detected atrial fibrillation after ischaemic stroke or TIA: A systematic review.

Background: Several molecular biomarkers are available that predict newly detected atrial fibrillation (NDAF). We aimed to identify such biomarkers that predict NDAF after an Ischaemic stroke (IS)/Transient Ischaemic Attack (TIA) and evaluate their performance.

Methods: A systematic review was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.

Xanthine oxidase inhibition and white matter hyperintensity progression following ischaemic stroke and transient ischaemic attack (XILO-FIST): a multicentre, double-blinded, randomised, placebo-controlled trial.

Background: People who experience an ischaemic stroke are at risk of recurrent vascular events, progression of cerebrovascular disease, and cognitive decline. We assessed whether allopurinol, a xanthine oxidase inhibitor, reduced white matter hyperintensity (WMH) progression and blood pressure (BP) following ischaemic stroke or transient ischaemic attack (TIA).

Methods: In this multicentre, prospective, randomised, double-blinded, placebo-controlled trial conducted in 22 stroke units in the United Kingdom, we randomly assigned participants within 30-days of ischaemic stroke or TIA to receive oral allopurinol 300 mg twice daily or placebo for 104 weeks.

Flow-Based Fmoc-SPPS Preparation and SAR Study of Cathelicidin-PY Reveals Selective Antimicrobial Activity.

Antimicrobial peptides (AMPs) hold promise as novel therapeutics in the fight against multi-drug-resistant pathogens. Cathelicidin-PY (NH-RKCNFLCKLKEKLRTVITSHIDKVLRPQG-COOH) is a 29-residue disulfide-cyclised antimicrobial peptide secreted as an innate host defence mechanism by the frog (PY) and reported to possess broad-spectrum antibacterial and antifungal properties, exhibiting low cytotoxic and low hemolytic activity. Herein, we detail the total synthesis of cathelicidin-PY using an entirely on-resin synthesis, including assembly of the linear sequence by rapid flow Fmoc-SPPS and iodine-mediated disulfide bridge formation.

Synthesis, Antibacterial Activity, and Nephrotoxicity of Polymyxin B Analogues Modified at Leu-7, d-Phe-6, and the N-Terminus Enabled by S-Lipidation.

With the post-antibiotic era rapidly approaching, many have turned their attention to developing new treatments, often by structural modification of existing antibiotics. Polymyxins, a family of lipopeptide antibiotics that are used as a last line of defense in the clinic, have recently developed resistance and exhibit significant nephrotoxicity issues. Using thiol-ene chemistry, the facile preparation of six unique S-lipidated building blocks was demonstrated and used to generate lipopeptide mimetics upon incorporation into solid-phase peptide synthesis (SPPS).

Improving detection and management of atrial fibrillation after ischaemic stroke in Glasgow (IMPROVE-AF): A quality improvement project.

Background: The use of cardiac monitoring to detect atrial fibrillation (AF) is routine after ischaemic stroke but is often delayed leaving patients at risk from undetected AF. We sought to improve the detection of AF by delivering early prolonged 'in-house' cardiac monitoring.

Methods: We collected 3-months of data of people with stroke/transient ischaemic attack (TIA), but without AF, who underwent cardiac monitoring (Phase 1, pre-quality improvement project (QIP)).

Synthetic Studies towards the Calcium-Dependent Lipopeptide Antibiotic Cadaside B.

In the current global crisis of antimicrobial resistance, antimicrobial peptides represent a promising source of alternative antibiotics. Recently discovered cadaside B, a novel calcium-dependent antibiotic, exhibits potent antimicrobial activity towards Gram-positive pathogens including multi-drug resistant strains. These properties, coupled with a novel structure, non-cytotoxicity, and low likelihood of developing resistance render cadaside B an important synthetic target.

Preventing Recurrent Cardioembolic Stroke: Right Approach, Right Patient (PRECISE) Study Protocol.

Cardiac rhythm monitoring is performed to search for atrial fibrillation (AF) after ischaemic stroke or transient ischaemic attack (TIA). Prolonged cardiac rhythm monitoring increases AF detection but is challenging to implement in many healthcare settings and is not needed for all people after ischaemic stroke/TIA. We aimed to develop and validate a model that includes clinical, electrocardiogram (ECG), blood-based, and genetic biomarkers to identify people with a low probability of AF detection after ischaemic stroke or TIA.

Stereochemical Effects on the Antimicrobial Properties of Tetrasubstituted 2,5-Diketopiperazines.

Antimicrobial drug resistance is a looming health crisis facing us in the modern era, and new drugs are urgently needed to combat this growing problem. Synthetic mimics of antimicrobial peptides have recently emerged as a promising class of compounds for the treatment of persistent microbial infections. In the current study, we investigate five cyclic -alkylated amphiphilic 2,5-diketopiperazines against 15 different strains of bacteria and fungi, including drug-resistant clinical isolates.

Leveraging Genetic Data to Elucidate the Relationship Between COVID-19 and Ischemic Stroke.

Background The relationship between COVID-19 and ischemic stroke is poorly understood due to potential unmeasured confounding and reverse causation. We aimed to leverage genetic data to triangulate reported associations. Methods and Results Analyses primarily focused on critical COVID-19, defined as hospitalization with COVID-19 requiring respiratory support or resulting in death.

Use of risk scores for predicting new atrial fibrillation after ischemic stroke or transient ischemic attack-A systematic review.

Background: Newly detected atrial fibrillation (NDAF) following an ischemic stroke or transient ischemic attack is often paroxysmal in nature. While challenging to detect, extended electrocardiographic (ECG) monitoring is often used to identify NDAF which has resource implications. Prognostic risk scores have been derived which may stratify the risk of NDAF and inform patient selection for ECG monitoring approaches after ischemic stroke/transient ischemic attack.

Biomarkers for Atrial Fibrillation Detection After Stroke: Systematic Review and Meta-analysis.

Background And Objective: To identify clinical, ECG, and blood-based biomarkers associated with atrial fibrillation (AF) detection after ischaemic stroke or TIA that could help inform patient selection for cardiac monitoring.

Methods: We performed a systematic review and meta-analysis and searched electronic databases for cohort studies from January 15, 2000, to January 15, 2020. The outcome was AF ≥30 seconds within 1 year after ischemic stroke/TIA.