Oral vancomycin treatment alters levels of indole derivatives and secondary bile acids modulating the expression of mTOR pathway genes in astrocytes during EAE.

Astrocytes play important roles in the central nervous system (CNS) during health and disease. Prior studies have shown that gut commensals derived indole derivatives as well as secondary bile acids modulate astrocyte function during the late stage of EAE (recovery phase). Here we show that administering vancomycin to mice starting during the early stage of EAE improved disease recovery, an effect that is mediated by the gut microbiota.

Multi-omic Biomarkers Distinguish Rheumatoid Arthritis in Discordant Monozygotic Twins.

Background: Although genetic factors have been identified in the pathogenesis of rheumatoid arthritis (RA), the concordance rate in monozygotic (MZ) twins is low, suggesting that other features contribute to disease development. Further, the relative contribution of such non-genetic elements in identical twins have not been characterized. Here, we aimed to measure differentiating host and microbial biomarkers of RA by studying MZ twins discordant for disease using a multi-omics approach.

Discovery of Potent, Highly Selective, and Efficacious SMARCA2 Degraders.

We describe the identification of selective SMARCA2, VHL-based heterobifunctional degraders. Structurally novel indolo[1,2-]quinazolin-5(7)-one SMARCA bromodomain binders were optimized and then converted to SMARCA2 degraders by linking them to well-defined VHL ligands. Our exploration led to the discovery of potent and selective degraders of SMARCA2 over the SMARCA4 paralog, leading to potent and selective growth inhibition of SMARCA4 mutant versus wild type cell lines.

Predicting poor functional outcomes for patients with large computed tomography perfusion core infarctions treated with endovascular thrombectomy.

Objective: Stroke patients with large core infarctions benefit from endovascular intervention, though only approximately 20% are functionally independent at 90 days. We studied prognostic factors for patients presenting with a large computed tomography perfusion (CTP) core.

Methods: Retrospective analysis from a health system stroke registry, including consecutive thrombectomy patients treated within 24 hours from August 2020-December 2022 with an anterior circulation large vessel occlusion and CTP core infarct ≥50 milliliters.

Bad company? The pericardium microbiome in people investigated for tuberculous pericarditis in an HIV-prevalent setting.

Background: The site-of-disease microbiome and predicted metagenome were evaluated in a cross-sectional study involving people with presumptive tuberculous pericarditis. We also explored the interaction between C-reactive protein (CRP) and the microbiome.

Methods: People with effusions requiring diagnostic pericardiocentesis (n=139) provided pericardial fluid for sequencing and blood for CRP measurement.

Subtracting the background by reducing cell-free DNA's confounding effects on Mycobacterium tuberculosis quantitation and the sputum microbiome.

DNA characterisation in people with tuberculosis (TB) is critical for diagnostic and microbiome evaluations. However, extracellular DNA, more frequent in people on chemotherapy, confounds results. We evaluated whether nucleic acid dyes [propidium monoazide (PMA), PEMAX] and DNaseI could reduce this.

PneumoniaCheck, a novel aerosol collection device, permits capture of airborne Mycobacterium tuberculosis and characterisation of the cough aeromicrobiome in people with tuberculosis.

Background: Tuberculosis (TB), a major cause of disease and antimicrobial resistance, is spread via aerosols. Aerosols have diagnostic potential and airborne-microbes other than Mycobacterium tuberculosis complex (MTBC) may influence transmission. We evaluated whether PneumoniaCheck (PMC), a commercial aerosol collection device, captures MTBC and the aeromicrobiome of people with TB.

Early recanalization after tenecteplase versus alteplase: Experience in a large stroke network.

Introduction: Previously published data are conflicting regarding the ability of tenecteplase versus alteplase to produce early recanalization of an intracranial large vessel occlusion. We compared the performance of each thrombolytic in a stroke network.

Methods: We queried our prospectively collected code stroke registry for basilar, internal carotid, or proximal middle cerebral artery occlusion patients treated with intravenous thrombolysis from 11/17/2021-9/16/2023.

Neurological outcomes for patients meeting radiographic criteria for DEFUSE 3 and SELECT2.

Background: The DEFUSE 3 and SELECT2 thrombectomy trials included some patients with similar radiographic profiles, although the rates of good functional outcomes differed widely between the studies.

Objective: To report neurological outcomes for patients who meet CT and CT perfusion (CTP) inclusion criteria common to both DEFUSE 3 and SELECT2.

Methods: Retrospective study of thrombectomy patients, presenting between November 2016 and December 2023 to a large health system, with Alberta Stroke Program Early CT score ≥6, core infarction 50-69 mL, mismatch ratio ≥1.

Latent Tuberculosis Infection Is Associated with an Enrichment of Short-Chain Fatty Acid-Producing Bacteria in the Stool of Women Living with HIV.

Latent tuberculosis infection (LTBI) is common in people living with HIV (PLHIV) in high-TB-burden settings. Active TB is associated with specific stool taxa; however, little is known about the stool microbiota and LTBI in PLHIV. We characterised the stool microbiota of PLHIV with [interferon- release assay (IGRA)- and tuberculin skin test (TST)-positive] or without (IGRA- and TST-negative) LTBI ( = 25 per group).

Bad company? The pericardium microbiome in people investigated for tuberculosis pericarditis in an HIV-prevalent setting.

Background: The microbiome likely plays a role in tuberculosis (TB) pathogenesis. We evaluated the site-of-disease microbiome and predicted metagenome in people with presumptive tuberculous pericarditis, a major cause of mortality, and explored for the first time, the interaction between its association with C-reactive protein (CRP), a potential diagnostic biomarker and the site-of-disease microbiome in extrapulmonary TB.

Methods: People with effusions requiring diagnostic pericardiocentesis (n=139) provided background sampling controls and pericardial fluid (PF) for 16S rRNA gene sequencing analysed using QIIME2 and PICRUSt2.

A novel aerosol collection method shows the cough aeromicrobiome of people with tuberculosis is phylogenetically distinct from respiratory tract specimens.

Background: Tuberculosis (TB), a major cause of disease and antimicrobial resistance, is spread via aerosols. Aerosols have diagnostic potential and airborne-microbes other than (MTBC) may influence transmission. We evaluated whether PneumoniaCheck (PMC), a commercial aerosol collection device, captures MTBC and the aeromicrobiome of people with TB.

Latent tuberculosis infection is associated with an enrichment of short chain fatty acid producing bacteria in the stool of women living with HIV.

Background: Latent tuberculosis infection (LTBI) is common in people living with HIV (PLHIV) in high TB burden settings. Active TB is associated with specific stool taxa; however, little is known about the stool microbiota and LTBI, including in PLHIV.

Method: Within a parent study that recruited adult females with HIV from Cape Town, South Africa into predefined age categories (18-25, 35-60 years), we characterised the stool microbiota of those with [interferon-γ release assay (IGRA)- and tuberculin skin test (TST)-positive] or without (IGRA- and TST- negative) LTBI (n=25 per group).

Group Acceptance and Commitment Therapy for Recovery From Psychosis: Protocol for a Single-Group Waitlist Trial.

Background: Psychological interventions, along with antipsychotic medications, are recommended for adults diagnosed with a psychotic disorder. While initially designed to mitigate positive symptoms, psychological interventions targeting personal recovery were developed and aligned with the recovery framework that many mental health services have adopted. Acceptance and Commitment Therapy (ACT) for psychosis is one such intervention that shows promise when delivered in an individual format.

Acceptability and feasibility of recovery-oriented group acceptance and commitment therapy for psychosis in routine practice: an uncontrolled pilot study.

Background: Personal recovery is a persisting concern for people with psychotic disorders. Accordingly, mental health services have adopted frameworks of personal recovery, prioritizing adaptation to psychosis alongside symptom remission. Group acceptance and commitment therapy (ACT) for psychosis aims to promote personal recovery alongside improved mood and quality of life.

Predictors of devastating functional outcome despite successful basilar thrombectomy.

Background: Basilar thrombosis frequently leads to poor functional outcomes, even with good endovascular reperfusion. We studied factors associated with severe disability or death in basilar thrombectomy patients achieving revascularization.

Methods: We retrospectively analyzed records from a health system's code stroke registry, including successful basilar thrombectomy patients from January 2017 to May 2023 who were evaluated with pretreatment computed tomography perfusion.

Oral vancomycin treatment suppresses gut trypsin activity and preserves intestinal barrier function during EAE.

Studies have reported increased intestinal permeability in multiple sclerosis (MS) patients and its mouse model experimental autoimmune encephalomyelitis (EAE). However, the mechanisms driving increased intestinal permeability that in turn exacerbate neuroinflammation during EAE remain unclear. Here we showed that vancomycin preserved the integrity of the intestinal barrier, while also suppressing gut trypsin activity, enhancing the relative abundance of specific and ameliorating disease during EAE.

Prostate MR image quality of apparent diffusion coefficient maps versus fractional intracellular volume maps from VERDICT MRI using the PI-QUAL score and a dedicated Likert scale for artefacts.

Purpose: This study aimed to assess the image quality of apparent diffusion coefficient (ADC) maps derived from conventional diffusion-weighted MRI and fractional intracellular volume maps (FIC) from VERDICT MRI (Vascular, Extracellular, Restricted Diffusion for Cytometry in Tumours) in patients from the INNOVATE trial. The inter-reader agreement was also assessed.

Methods: Two readers analysed both ADC and FIC maps from 57 patients enrolled in the INNOVATE prospective trial.

Lower Airway Dysbiosis Augments Lung Inflammatory Injury in Mild-to-Moderate Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and healthcare costs. Cigarette smoke is a causative factor; however, not all heavy smokers develop COPD. Microbial colonization and infections are contributing factors to disease progression in advanced stages.

The Charlotte Large artery occlusion Endovascular therapy Outcome Score predicts independent outcome after thrombectomy.

Background And Purpose: Predicting functional outcomes after endovascular thrombectomy (EVT) is of interest to patients and families as they navigate hospital and post-acute care decision-making. We evaluated the prognostic ability of several scales to predict good neurological function after EVT.

Methods: We retrospectively analyzed records from a health system's code stroke registry, including consecutive successful thrombectomy patients from August 2020 to February 2023 presenting with an anterior circulation large vessel occlusion who were evaluated with pre-EVT CT perfusion.