Bacterial peptidoglycan, the essential cell surface polymer that protects bacterial integrity, also serves as the molecular pattern recognized by the host's innate immune system. Although the minimal motifs of bacterial peptidoglycan fragments (PGNs) that activate mammalian NOD1 and NOD2 sensors are well-known and often represented by small canonical ligands, the immunostimulatory effects of natural PGNs, which are structurally more complex and potentially can simultaneously activate both the NOD1 and NOD2 signaling pathways in hosts, have not been comprehensively investigated. In particular, many bacteria incorporate additional structural modifications in peptidoglycans to evade host immune surveillance, resulting in diverse structural variations among natural PGNs that may influence their biological effects in hosts.
View Article and Find Full Text PDFPurpose: Increased prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) highlights a desire for screening with liver ultrasound normalized local variance (NLV). We aimed to assess variations in NLV values measured at different sampling depths and discuss common technical considerations in measuring liver NLV.
Methods: We retrospectively measured liver NLVs at variable depths on ultrasound images pre-recorded in 116 participants who underwent liver magnetic resonance imaging-proton density fat fraction (MRI-PDFF) and ultrasound to screen for MASLD.
is a common opportunistic fungus in humans, whose morphological switch between yeast and hyphae forms represents a key virulence trait. Developing strategies to inhibit hyphal growth may provide insights into designs of novel antivirulent therapeutics. Importantly, the gut commensal bacterium, , secretes a bacteriocin EntV which has potent antivirulent and antifungal effects against in infection models; however, hampered by the challenges to access large quantities of bioactive EntV, the detailed understanding of its mechanisms on has remained elusive.
View Article and Find Full Text PDFCorrection for 'A closer look at ligand specificity for cellular activation of NOD2 with synthetic muramyl dipeptide analogues' by Christopher Adamson , , 2024, , 2212-2215, https://doi.org/10.1039/D3CC05807G.
View Article and Find Full Text PDFBackground: Guidelines for the management of cardiovascular disease (CVD) recommend preconception risk stratification and counselling in all women of childbearing age. We assessed the provision of preconception counselling (PCC) among women of reproductive age attending general cardiology outpatient clinics over a 12-month period in two large health boards in Scotland.
Methods And Results: Electronic health records were reviewed and data on patient demographics, cardiac diagnoses, medication use and the content of documented discussions regarding PCC were recorded.
The delineation of cortical areas on magnetic resonance images (MRI) is important for understanding the complexities of the developing human brain. The previous version of the Melbourne Children's Regional Infant Brain (M-CRIB-S) (Adamson et al. Scientific Reports, 10(1), 10, 2020) is a software package that performs whole-brain segmentation, cortical surface extraction and parcellation of the neonatal brain.
View Article and Find Full Text PDFTo further understand the specificity of muramyl dipeptide (MDP) sensing by NOD2, we evaluated the compatibility of synthetic MDP analogues for cellular uptake and NAGK phosphorylation, the pre-requisite steps of intracellular NOD2 activation. Our results revealed that these two prior steps do not confer ligand stereoselectivity; yet NAGK strictly discriminates against the disaccharide NOD2 agonists for phosphorylation , despite it being indispensable for the cellular NOD2-stimulating effects of these analogues, implying potential glycosidase cleavage as a novel intermediate step for cellular activation of NOD2.
View Article and Find Full Text PDFAppl Environ Microbiol
February 2024
Anti-viral surface coatings are under development to prevent viral fomite transmission from high-traffic touch surfaces in public spaces. Copper's anti-viral properties have been widely documented, but the anti-viral mechanism of copper surfaces is not fully understood. We screened a series of metal and metal oxide surfaces for anti-viral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease (COVID-19).
View Article and Find Full Text PDFAims: Neuropeptide Y (NPY) is the most abundant neuropeptide found in the heart and is released alongside norepinephrine following prolonged sympathetic activation, a process that is implicated in the pathophysiology of heart failure (HF). In patients with severely impaired left ventricular ejection fraction (LVEF) undergoing cardiac resynchronization therapy, higher levels of NPY measured in coronary sinus blood, are associated with poorer outcome. The aim was to examine the association of peripheral venous NPY levels and outcomes in a HF population with a range of LVEF, using a highly sensitive and specific assay.
View Article and Find Full Text PDFEarly life experiences can exert a significant influence on cortical and cognitive development. Very preterm birth exposes infants to several adverse environmental factors during hospital admission, which affect cortical architecture. However, the subsequent consequence of very preterm birth on cortical growth from infancy to adolescence has never been defined; despite knowledge of critical periods during childhood for establishment of cortical networks.
View Article and Find Full Text PDFAims: Although trials have proven the group-level effectiveness of various therapies for heart failure with reduced ejection fraction (HFrEF), important differences in absolute effectiveness exist between individuals. We developed and validated the LIFEtime-perspective for Heart Failure (LIFE-HF) model for the prediction of individual (lifetime) risk and treatment benefit in patients with HFrEF.
Methods And Results: Cox proportional hazards functions with age as the time scale were developed in the PARADIGM-HF and ATMOSPHERE trials (n = 15 415).
Background: Spinal cord injury (SCI) causes neural disconnection and persistent neurological deficits, so axon sprouting and plasticity might promote recovery. Soluble Nogo-Receptor-Fc decoy (AXER-204) blocks inhibitors of axon growth and promotes recovery of motor function after SCI in animals. This first-in-human and randomised trial sought to determine primarily the safety and pharmacokinetics of AXER-204 in individuals with chronic SCI, and secondarily its effect on recovery.
View Article and Find Full Text PDFBackground: Anemia is common in patients with heart failure with reduced ejection fraction and is associated with poor clinical outcomes. Renin-angiotensin system blockers lower hemoglobin and may induce anemia.
Objectives: The authors investigated whether concomitant neprilysin inhibition might ameliorate this effect of renin-angiotensin system blockers in PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure).
Aim: Patients with heart failure (HF) often suffer from a range of comorbidities, which may affect their health status. The aim of this study was to assess the impact of different comorbidities on health status in patients with HF and reduced (HFrEF) and preserved ejection fraction (HFpEF).
Methods And Results: Using individual patient data from HFrEF (ATMOSPHERE, PARADIGM-HF, DAPA-HF) and HFpEF (TOPCAT, PARAGON-HF) trials, we examined the Kansas City Cardiomyopathy Questionnaire (KCCQ) domain scores and overall summary score (KCCQ-OSS) across a range of cardiorespiratory (angina, atrial fibrillation [AF], stroke, chronic obstructive pulmonary disease [COPD]) and other comorbidities (obesity, diabetes, chronic kidney disease [CKD], anaemia).
Aim: Although education in self-management is thought to be an important aspect of the care of patients with heart failure, little is known about whether self-rated knowledge of self-management is associated with outcomes. The aim of this study was to assess the relationship between patient-reported knowledge of self-management and clinical outcomes in patients with heart failure and reduced ejection fraction (HFrEF).
Methods And Results: Using individual patient data from three recent clinical trials enrolling participants with HFrEF, we examined patient characteristics and clinical outcomes according to responses to the 'self-efficacy' questions of the Kansas City Cardiomyopathy Questionnaire.
Background: Joint modelling combines two or more statistical models to reduce bias and increase efficiency. As the use of joint modelling increases it is important to understand how and why it is being applied to heart failure research.
Methods: A systematic review of major medical databases of studies which used joint modelling within heart failure alongside an exemplar; joint modelling repeat measurements of serum digoxin with all-cause mortality using data from the Effect of Digoxin on Mortality and Morbidity in Patients with Heart Failure (DIG) trial.
Background: Inflammation may play a role in the pathophysiology of heart failure with preserved ejection fraction. We examined whether circulating levels of interleukin-6 identify patients at greater risk of adverse outcomes following hospitalization with heart failure with preserved ejection fraction.
Methods: We assessed relationships between interleukin-6 (IL-6) tertiles (T1-3) and all-cause death, cardiovascular death, and subsequent heart failure hospitalization (sHFH) in 286 patients recently hospitalized with heart failure with preserved ejection fraction.
Purpose: To assess diagnostic performance of quantitative ultrasound (QUS) biomarkers in assessing hepatic steatosis.
Methods: We prospectively recruited 125 participants (mean age 54 years) who underwent liver QUS, magnetic resonance imaging (MRI), and laboratory tests within 30 days in this IRB approved study. Based on MRI-proton density fat fraction (MRI-PDFF) and MRE, we divided 125 participants into normal liver, nonalcoholic fatty liver (NAFL) and liver fibrosis (≥F1) groups.
Aims: Few reports have examined the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) or their relationship with mortality in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF).
Methods And Results: Data from the PARAGON-HF, TOPCAT, I-Preserve, and CHARM-Preserved trials were merged. VT/VF, reported as adverse events, were identified.
Background: Insulin-like growth factor-binding protein-7 (IGFBP-7) has been proposed as a potential prognostic biomarker in heart failure (HF), but the association between elevation in IGFBP-7 and HF outcomes in ambulant patients with heart failure with reduced ejection fraction (HFrEF) is unknown.
Objectives: The authors addressed this question in a post hoc analysis of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial.
Methods: The primary outcome was a composite of cardiovascular death or a worsening HF event.
Unlabelled: Coronary perforation is a potentially life-threatening complication of percutaneous coronary intervention (PCI). We studied incidence, outcomes and temporal trends following PCI-related coronary artery perforation (CAP).
Methods: Prospective systematic review and meta-analysis including meta-regression using MEDLINE and EMBASE to November 2020.
Background The objective of the GNOCCI (Glasgow Natural History Study of Covered Stent Coronary Interventions) Study was to report the incidence and outcomes of coronary artery perforations over an 18-year period at a single, high-volume percutaneous coronary intervention center. We considered both the temporal trends and long-term outcomes of covered stent deployment. Methods and Results We evaluated procedural and long-term clinical outcomes following coronary perforation in a cohort of 43,343 consecutive percutaneous coronary intervention procedures.
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