Quorum sensing signals of the grapevine crown gall bacterium, sp. Rr2-17: use of inducible expression and polymeric resin to sequester acyl-homoserine lactones.

Background: A grapevine crown gall tumor strain, sp. strain Rr2-17 was previously reported to accumulate copious amounts of diverse quorum sensing signals during growth. Genome sequencing identified a single luxI homolog in strain Rr2-17, suggesting that it may encode for a AHL synthase with broad substrate range, pending functional validation.

Physiotherapists' Experiences and Perceived Acceptability of Delivering a Knee Bracing Intervention for People With Symptomatic Knee Osteoarthritis in a Randomised Trial (PROP OA): A Qualitative Study.

Objectives: To explore physiotherapists' experiences and perceived acceptability of delivering a bracing intervention for knee osteoarthritis (OA) in the 'PROvision of braces for Patients with knee OA' (PROP OA) randomised controlled trial.

Method: Semi-structured telephone interviews with consenting physiotherapists who received the PROP OA training programme and delivered the knee bracing intervention (advice, information and exercise instruction plus knee brace matched to patients' clinical and radiographic presentation and with adherence support). Interviews were recorded and transcribed verbatim.

Efficacy and safety of palliative treatment in patients with autoimmune liver disease-associated hepatocellular carcinoma.

Introduction And Objectives: Autoimmune liver diseases (AILD) are rare causes hepatocellular carcinoma (HCC), and data on the efficacy and tolerability of anti-tumor therapies are scarce. This pan-European study aimed to assess outcomes in AILD-HCC patients treated with tyrosine kinase inhibitors (TKIs) or transarterial chemoembolization (TACE) compared with patients with more common HCC etiologies, including viral, alcoholic or non-alcoholic fatty liver disease.

Materials And Methods: 107 patients with HCC-AILD (AIH:55; PBC:52) treated at 13 European centres between 1996 and 2020 were included.

Design, Synthesis, and Evaluation of New 1-Benzo[]imidazole Based PqsR Inhibitors as Adjuvant Therapy for Infections.

is one of the top priority pathogens that requires immediate attention according to the World Health Organisation (WHO). Due to the alarming shortage of novel antimicrobials, targeting quorum sensing (QS), a bacterial cell to cell signaling system controlling virulence, has emerged as a promising approach as an antibiotic adjuvant therapy. Interference with the system, one of three QS systems in , results in reduction of bacterial virulence gene expression and biofilm maturation.

Common variable immunodeficiency disorder-related liver disease is common and results in portal hypertension and an increased risk of death.

Background: Common variable immunodeficiency disorder (CVID) manifests with recurrent infections and inflammatory complications, including liver disease. We report the clinical features, natural history, and outcomes of patients with CVID-related liver disease (CVID-rLD) from a tertiary immunology and hepatology center.

Methods: Two hundred eighteen patients were identified; CVID-rLD was defined by persistently abnormal liver function tests or evidence of chronic liver disease (CLD) or portal hypertension (PHTN) by radiological or endoscopic investigation, after exclusion of other causes.

Common variable immunodeficiency disorder (CVID)-related liver disease: assessment of the main histological aspects using novel semiquantitative scoring systems, image analysis and correlation with clinical parameters of liver stiffness and portal hypertension.

Aims: We aimed to investigate the relationship between T-cell-mediated sinusoidal injury, nodular regenerative hyperplasia like changes (NRH-LC) and fibrosis, clinical measures of fibrosis and portal hypertension, and progression rate in common variable immunodeficiency disorder (CVID)-related liver disease.

Methods: This is a retrospective single-centre study. Liver biopsies from CVID patients with liver disease were reviewed to assess for NRH-LC, fibrosis and elastosis, including collagen and elastin proportionate areas.

Alkyl-quinolone-dependent quorum sensing controls prophage-mediated autolysis in colony biofilms.

is a model quorum sensing (QS) pathogen with three interconnected QS circuits that control the production of virulence factors and antibiotic tolerant biofilms. The QS system of is responsible for the biosynthesis of diverse 2-alkyl-4-quinolones (AQs), of which 2-heptyl-4-hydroxyquinoline (HHQ) and 2-heptyl-3-hydroxy-4()-quinolone (PQS) function as QS signal molecules. Transcriptomic analyses revealed that HHQ and PQS influenced the expression of multiple genes via PqsR-dependent and -independent pathways whereas 2-heptyl-4-hydroxyquinoline -oxide (HQNO) had no effect on transcriptome.

Growth rate and nutrient limitation as key drivers of extracellular quorum sensing signal molecule accumulation in .

In , quorum sensing (QS) depends on an interconnected regulatory hierarchy involving the Las, Rhl and Pq systems, which are collectively responsible for the co-ordinated synthesis of a diverse repertoire of -acylhomoserine lactones (AHLs) and 2-alkyl-4-quinolones (AQs). Apparent population density-dependent phenomena such as QS may, however, be due to growth rate and/or nutrient exhaustion in batch culture. Using continuous culture, we show that growth rate and population density independently modulate the accumulation of AHLs and AQs such that the highest concentrations are observed at a slow growth rate and high population density.

Design of Quorum Sensing Inhibitor-Polymer Conjugates to Penetrate Biofilms.

Antimicrobial resistance (AMR) is a global threat to public health with a forecast of a negative financial impact of one trillion dollars per annum, hence novel therapeutics are urgently needed. The resistance of many bacteria against current drugs is further augmented by the ability of these microbes to form biofilms where cells are encased in a slimy extracellular matrix and either adhered to a surface or forming cell aggregates. Biofilms form physiochemical barriers against the penetration of treatments such as small molecule antibacterials, rendering most treatments ineffective.

The CTLA-4 immune checkpoint protein regulates PD-L1:PD-1 interaction via transendocytosis of its ligand CD80.

CTLA-4 and PD-1 are key immune checkpoint receptors that are targeted in the treatment of cancer. A recently identified physical interaction between the respective ligands, CD80 and PD-L1, has been shown to block PD-L1/PD-1 binding and to prevent PD-L1 inhibitory functions. Since CTLA-4 is known to capture and degrade its ligands via transendocytosis, we investigated the interplay between CD80 transendocytosis and CD80/PD-L1 interaction.

Bacterascites confers poor patient prognosis beyond MELD prediction.

Spontaneous bacterial peritonitis (SBP) is a well-recognized clinical entity with a poor prognosis. In comparison, the prevalence, microbiological flora, and prognostic significance of bacterascites (BA) (the presence of organism on culture but ascitic PMN <250 cells/mm³) is largely unknown. We, therefore, assessed the prognosis and predictors of outcome in patients with BA in comparison with those with SBP.

Outcomes After Liver Transplantation With Incidental Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is currently a contraindication to liver transplantation (LT) in the United Kingdom (UK). Incidental CCA occurs rarely in some patients undergoing LT. We report on retrospective outcomes of patients with incidental CCA from six UK LT centres.

Differences in CD80 and CD86 transendocytosis reveal CD86 as a key target for CTLA-4 immune regulation.

CD28 and CTLA-4 (CD152) play essential roles in regulating T cell immunity, balancing the activation and inhibition of T cell responses, respectively. Although both receptors share the same ligands, CD80 and CD86, the specific requirement for two distinct ligands remains obscure. In the present study, we demonstrate that, although CTLA-4 targets both CD80 and CD86 for destruction via transendocytosis, this process results in separate fates for CTLA-4 itself.

UK-Wide Multicenter Evaluation of Second-line Therapies in Primary Biliary Cholangitis.

Background & Aims: Thirty-to-forty percent of patients with primary biliary cholangitis inadequately respond to ursodeoxycholic acid. Our aim was to assemble national, real-world data on the effectiveness of obeticholic acid (OCA) as a second-line treatment, alongside non-licensed therapy with fibric acid derivatives (bezafibrate or fenofibrate).

Methods: This was a nationwide observational cohort study conducted from August 2017 until June 2021.

, gen. nov., sp. nov., isolated from the leafhopper .

Bacterial endosymbionts are found in multiple arthropod species, where they play crucial roles as nutritional symbionts, defensive symbionts or reproductive parasites. Recent work has highlighted a new clade of heritable microbes within the gammaproteobacteria that enter into both obligate and facultative symbioses, with an obligately required unculturable symbiont recently given the name Symbiopectobacterium. In this study, we describe a culturable rod shaped non-flagellated bacterial symbiont from this clade isolated from the leafhopper .

Patient Priorities in Autoimmune Hepatitis: The Need for Better Treatments, More Education and Challenging Stigma.

Background: Data show that patients with autoimmune hepatitis have significantly reduced quality-of-life and that corticosteroids carry marked side effects.

Aims: This study explored patients' experiences of autoimmune hepatitis and its treatments; key aspects for developing safe and effective new approaches to therapy.

Methods: An anonymised, internet-based survey collected data including patient demographics, treatments, side-effects, impact on day-to-day life, sources of support and attitudes towards autoimmune hepatitis between December 2019-January 2020.

Donor-recipient human leukocyte antigen A mismatching is associated with hepatic artery thrombosis, sepsis, graft loss, and reduced survival after liver transplant.

Human leukocyte antigen (HLA) matching is not routinely performed for liver transplantation as there is no consistent evidence of benefit; however, the impact of HLA mismatching remains uncertain. We explored the effect of class I and II HLA mismatching on graft failure and mortality. A total of 1042 liver transplants performed at a single center between 1999 and 2016 with available HLA typing data were included.

2-Alkyl-4-quinolone quorum sensing molecules are biomarkers for culture-independent burden in adults with cystic fibrosis.

produces quorum sensing signalling molecules including 2-alkyl-4-quinolones (AQs), which regulate virulence factor production in the cystic fibrosis (CF) airways. Culture can lead to condition-dependent artefacts which may limit the potential insights and applications of AQs as minimally-invasive biomarkers of bacterial load. We aimed to use culture-independent methods to explore the correlations between AQ levels and live load in adults with CF.

Novel detection of specific bacterial quorum sensing molecules in saliva: Potential non-invasive biomarkers for pulmonary Pseudomonas aeruginosa in cystic fibrosis.

Pseudomonas aeruginosa produces specific signalling molecules, 2-alkyl-4-quinolones (AQs) that are detectable in the sputum of adults with cystic fibrosis (CF) and who have pulmonary infection with this opportunistic pathogen. This study aimed to determine whether AQs could be detected in saliva of patients with CF and known infection with Pseudomonas aeruginosa. Saliva and sputum samples were obtained from 89 adults with CF and analyzed using liquid chromatography-tandem mass spectrometry.

Evaluation of distal radial artery cross-sectional internal diameter in neonates and infants by ultrasound and adequate selection of an intra-arterial catheter size.

Background: Radial artery catheterization in neonates, infants, and young children is a common and useful invasive procedure that brings technical placement challenges and potential complications due to the small diameter size of the radial artery in these patients. The aim of this study is to determine appropriate catheter sizes in infants up to 6 months of age.

Materials And Methods: A total of fifty infants undergoing general anesthesia or hospitalized in the neonatal intensive care unit were included.

Design and Evaluation of New Quinazolin-4(3)-one Derived PqsR Antagonists as Quorum Sensing Quenchers in .

(PA) continues to pose a threat to global public health due to its high levels of antimicrobial resistance (AMR). The ongoing AMR crisis has led to an alarming shortage of effective treatments for resistant microbes, and hence there is a pressing demand for the development of novel antimicrobial interventions. The potential use of antivirulence therapeutics to tackle bacterial infections has attracted considerable attention over the past decades as they hamper the pathogenicity of target microbes with reduced selective pressure, minimizing the emergence of resistance.