Objectives: To quantify the stage-shift with prostate-specific membrane antigen (PSMA) PET/CT imaging in metastatic prostate cancer and explore treatment implications.
Methods: Single-centre, retrospective analysis of patients with newly diagnosed [F]PSMA-1007 or [Ga]Ga-PSMA-11 PET/CT-detected metastatic prostate cancer who had baseline bone scintigraphy between January 2015 and May 2021. Patients were subclassified into oligometastatic and polymetastatic disease utilizing the STAMPEDE2 trial (ISRCTN66357938/NCT06320067) definition.
Background: Meniscus root tears comprise 10% to 21% of all meniscal tears. These tears alter knee biomechanics, elevating contact pressure, akin to a meniscectomy. Consequently, they are linked to advanced joint degeneration and cartilage damage in the affected compartment.
View Article and Find Full Text PDFHerein, we report the synthesis of extended sulfo-pillar[6]arenes (), a new host class with a pedigree in salt tolerance and ultrahigh binding affinity toward multiple drug classes. The parent sulfo-pillar[6]arene is a high-affinity host with the potential to act as a supramolecular reversal agent. However, it lacks synthetic diversification of the core scaffold.
View Article and Find Full Text PDFMultiligament knee injuries (MLKIs) represent a broad spectrum of pathology with potentially devastating consequences. Currently, disagreement in the terminology, diagnosis and treatment of these injuries limits clinical care and research. This study aimed to develop consensus on the nomenclature, diagnosis, treatment and rehabilitation strategies for patients with MLKI, while identifying important research priorities for further study.
View Article and Find Full Text PDFSphingolipids play vital roles in metabolism and regulation. Previously, the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, was reported to directly regulate ceramide synthesis genes by binding to their promoters. Herein, sphingosine kinase 2 (SPHK2), responsible for producing sphingosine-1-phosphate (S1P), was found to interact with AHR through LXXLL motifs, influencing AHR nuclear localization.
View Article and Find Full Text PDFBackground: Exposure to persistent organic pollutants (POPs) and disruptions in the gastrointestinal microbiota have been positively correlated with a predisposition to factors such as obesity, metabolic syndrome, and type 2 diabetes; however, it is unclear how the microbiome contributes to this relationship.
Objective: This study aimed to explore the association between early life exposure to a potent aryl hydrocarbon receptor (AHR) agonist and persistent disruptions in the microbiota, leading to impaired metabolic homeostasis later in life.
Methods: This study used metagenomics, nuclear magnetic resonance (NMR)- and mass spectrometry (MS)-based metabolomics, and biochemical assays to analyze the gut microbiome composition and function, as well as the physiological and metabolic effects of early life exposure to 2,3,7,8-tetrachlorodibenzofuran (TCDF) in conventional, germ-free (GF), and -null mice.
Background: The health benefits of physical activity are well recognised. This study assessed whether golfers were more physically active after lower limb arthroplasty when compared to those that did not play golf (primary outcome). In addition pre and postoperative changes in health-associated quality of life (HAQoL) and joint specific outcomes between golfers and none golfers were assessed (secondary outcomes).
View Article and Find Full Text PDFPurpose: To evaluate and synthesize the available literature related to platelet-rich plasma (PRP) treatment of knee pathologies and to provide recommendations to inform future research in the field.
Methods: PubMed, CINAHL, and Scopus databases were queried on October 6, 2023. All identified citations were collated and uploaded into Covidence for screening and data extraction.
Low back pain (LBP) is the most common injury in golfers of all abilities. The primary aim of this review was to improve understanding of human golf swing biomechanics associated with LBP. A systematic review using the PRISMA guidelines was performed.
View Article and Find Full Text PDFThe intestinal epithelial layer is susceptible to damage by chemical, physiological and mechanical stress. While it is essential to maintain the integrity of epithelium, the biochemical pathways that contribute to the barrier function have not been completely investigated. Here we demonstrate an aryl hydrocarbon receptor (AHR)-dependent mechanism facilitating the production of the antimicrobial peptide AMP regenerating islet-derived protein 3 gamma (REG3G), which is essential for intestinal homeostasis.
View Article and Find Full Text PDFThe COVID-19 pandemic had a major impact on cancer patients and services but has been difficult to quantify. We examined how the entire cancer pathway-from incidence, presentation, diagnosis, stage, treatment and survival-was affected in Northern Ireland during April-December 2020 compared to equivalent 2018-2019 periods using retrospective, observational cancer registry data from the Northern Ireland Cancer Registry (NICR). There were 6748 cancer cases in April-December 2020 and an average 7724 patients in April-December 2018-2019.
View Article and Find Full Text PDFUnlabelled: Early energy analyses of agriculture revealed that behind higher labor and land productivity of industrial farming, there was a decrease in energy returns on energy (EROI) invested, in comparison to more traditional organic agricultural systems. Studies on recent trends show that efficiency gains in production and use of inputs have again somewhat improved energy returns. However, most of these agricultural energy studies have focused only on external inputs at the crop level, concealing the important role of internal biomass flows that livestock and forestry recirculate within agroecosystems.
View Article and Find Full Text PDFBackground: Radium-223 is a bone-seeking, ɑ-emitting radionuclide used to treat men with bone metastases from castration-resistant prostate cancer. Sclerotic bone lesions cannot be evaluated using Response Evaluation Criteria in Solid Tumors. Therefore, imaging response biomarkers are needed.
View Article and Find Full Text PDFAcyltransferases (AT) are enzymes that catalyze the transfer of acyl group to a receptor molecule. This review focuses on ATs that act on thioester-containing substrates. Although many ATs can recognize a wide variety of substrates, sequence similarity analysis allowed us to classify the ATs into fifteen distinct families.
View Article and Find Full Text PDFThe aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that plays an important role in gastrointestinal barrier function, tumorigenesis, and is an emerging drug target. The resident microbiota is capable of metabolizing tryptophan to metabolites that are AHR ligands (e.g.
View Article and Find Full Text PDFBackground: The quinoline-3-carboxamide, Tasquinimod (TasQ), is orally active as a maintenance therapy with an on-target mechanism-of-action via allosteric binding to HDAC4. This prevents formation of the HDAC4/NCoR1/HDAC3 complex, disrupting HIF-1α transcriptional activation and repressing MEF-2 target genes needed for adaptive survival signaling in the compromised tumor micro environment. In phase 3 clinical testing against metastatic castration-resistant prostate cancer(mCRPC), TasQ (1 mg/day) increased time-to-progression, but not overall survival.
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