The gut-liver axis in progressive steatotic liver disease: A focus on bile acid dysregulation.

Introduction: The gut-liver axis regulates metabolic homeostasis, with bile acids (BAs) serving as key signalling molecules. BA dysregulation is implicated in metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction- and alcohol-associated liver disease (MetALD), yet consistent identification of BA markers and their mechanistic roles across different stages of these diseases remain elusive.

Methods: We integrated three complementary studies to examine BA dysregulation: a population-based cohort (1522 females from TwinsUK with serum BA and liver biomarker data), a clinical cohort (30 patients with steatotic liver disease, fibrosis stages F0-F4, and 4 controls), and rodent models (20 rats with MASLD/MetALD vs.

Common inflammatory proteins linking frailty and area-level deprivation as key drivers of cardiovascular risk in women.

Background: Chronic inflammation is linked to frailty and deprivation, both of which are comorbid with cardiovascular diseases (CVD). This study aims to identify inflammatory proteins associated with both socioeconomic deprivation and frailty, and assess their role in mediating cardiovascular risk in a large cohort with independent replication.

Methods: We included 2144 TwinsUK females aged 37-84 with concurrent measures of frailty (frailty index), index of multiple deprivation (IMD), cardiovascular risk (ASCVD score), and 74 proteins (Olink inflammation panel).

Posterior monolithic 3-unit zirconia fixed dental prostheses: one-year interim results of a multicenter randomized clinical trial.

Objectives: To compare the survival rates and clinical outcomes of posterior 3-unit monolithic zirconia fixed dental prostheses (FDPs) to veneered zirconia FDPs.

Methods: Sixty-four patients missing single teeth in the posterior mandible or maxilla were recruited. Patients' restorations were randomly allocated to three groups: 1) monolithic zirconia FDPs (Mono-FDP, n = 21); 2) partially veneered zirconia FDPs (PV-FDP, n = 21); 3) circumferentially veneered zirconia FDPs (V-FDP, n = 22).

Translational genomics of osteoarthritis in 1,962,069 individuals.

Osteoarthritis is the third most rapidly growing health condition associated with disability, after dementia and diabetes. By 2050, the total number of patients with osteoarthritis is estimated to reach 1 billion worldwide. As no disease-modifying treatments exist for osteoarthritis, a better understanding of disease aetiopathology is urgently needed.

Multifluid Metabolomics Identifies Novel Biomarkers for Irritable Bowel Syndrome.

: Irritable bowel syndrome (IBS) is a complex disorder affecting 10% of the global population, but the underlying mechanisms remain poorly understood. By integrating multifluid metabolomics, we aimed to identify metabolite markers of IBS in a large population-based cohort. : We included individuals from TwinsUK with and without IBS, ascertained using the Rome III criteria, and analysed serum (232 cases, 1707 controls), urine (185 cases, 1341 controls), and stool (186 cases, 1284 controls) metabolites (Metabolon Inc.

Monocyte eukaryotic initiation factor 2 signaling differentiates 17-hydroxy-docosahexaenoic acid levels and pain.

Our goal was to probe the potential transcriptomic basis for the relationship between plasma levels of the specialized pro-resolving precursor, 17-hydroxy-docosahexaenoic acid (17-HDHA) and chronic pain. Participants with osteoarthritis (average age of 62.3, 60% were female,  = 30) were stratified by levels of 17-HDHA and self-reported pain scores.

Quantification of heavy metal exposure in a British population cohort links total mercury levels in plasma with skin tissue-specific changes in mitochondrial-related gene expression.

Heavy metals in our direct environment have profound effects on human health and while some are essential for life, others can be toxic. In vivo studies often focus on clinical features caused by overexposure to, or by deprivation of a heavy metal. However, to understand the cellular impact of heavy metals on health, studies in healthy volunteers before symptom onset are needed.

Development of methodology to support molecular endotype discovery from synovial fluid of individuals with knee osteoarthritis: The STEpUP OA consortium.

Objectives: To develop a protocol for largescale analysis of synovial fluid proteins, for the identification of biological networks associated with subtypes of osteoarthritis.

Methods: Synovial Fluid To detect molecular Endotypes by Unbiased Proteomics in Osteoarthritis (STEpUP OA) is an international consortium utilising clinical data (capturing pain, radiographic severity and demographic features) and knee synovial fluid from 17 participating cohorts. 1746 samples from 1650 individuals comprising OA, joint injury, healthy and inflammatory arthritis controls, divided into discovery (n = 1045) and replication (n = 701) datasets, were analysed by SomaScan Discovery Plex V4.

Supplementation with Citrus Low-Methoxy Pectin Reduces Levels of Inflammation and Anxiety in Healthy Volunteers: A Pilot Controlled Dietary Intervention Study.

Although low-methoxy (LM) pectin (polysaccharides extracted from citrus peels) can reduce inflammation by binding to and inhibiting the TLR-2 pathway in animal models and in vitro studies, the anti-inflammatory effects of LM pectin in humans and mood have not been explored to date. The purpose of this study is to assess the role of dietary supplementation with LM pectin in healthy volunteers on inflammatory markers and on mood, specifically anxiety and depression. We carried out a 4-week dietary intervention with LM citrus pectin on healthy volunteers (N = 14, age 40 ± 16 y, BMI 24.

Physical Therapy for Knee Pain Relief Induces Changes in Gut Microbiome Composition: A Secondary Analysis of Data From a Randomized Controlled Trial.

Background: Aerobic exercise alters gut microbiome composition, yet the impact of gentle physiotherapy on gut microbiome and its relation to muscle strengthening and physical function remains unexplored.

Hypothesis: Physiotherapy exercises modulate gut microbiome composition and changes in gut microbes are linked to improvements in muscle strength or function.

Study Design: Secondary data analysis of samples from a randomized controlled trial.

Metagenomic changes in response to antibiotic treatment in severe orthopedic trauma patients.

We investigated changes in microbiome composition and abundance of antimicrobial resistance (AMR) genes post-antibiotic treatment in severe trauma patients. Shotgun sequencing revealed beta diversity (Bray-Curtis) differences between 16 hospitalized multiple rib fractures patients and 10 age- and sex-matched controls ( = 0.043), and between antibiotic-treated and untreated patients ( = 0.

Vitamin A carotenoids, but not retinoids, mediate the impact of a healthy diet on gut microbial diversity.

Background: Vitamin A is essential for physiological processes like vision and immunity. Vitamin A's effect on gut microbiome composition, which affects absorption and metabolism of other vitamins, is still unknown. Here we examined the relationship between gut metagenome composition and six vitamin A-related metabolites (two retinoid: -retinol, 4 oxoretinoic acid (oxoRA) and four carotenoid metabolites, including beta-cryptoxanthin and three carotene diols).

Association of serum biomarkers with radiographic knee osteoarthritis, knee pain and function in a young, male, trauma-exposed population - Findings from the ADVANCE study.

Objective: The ArmeD SerVices TrAuma RehabilitatioN OutComE (ADVANCE) study is investigating long-term combat-injury outcomes; this sub-study aims to understand the association of osteoarthritis (OA) biomarkers with knee radiographic OA (rOA), pain and function in this high-risk population for post-traumatic OA.

Design: ADVANCE compares combat-injured participants with age, rank, deployment and job-role frequency-matched uninjured participants. Post-injury immunoassay-measured serum biomarkers, knee radiographs, Knee Injury and Osteoarthritis Outcome Scale, and six-minute walk tests are reported.

Preoperative inflammatory biomarkers reveal renal involvement in postsurgical mortality in hip fracture patients: an exploratory study.

Background: Hip fractures in frail patients result in excess mortality not accounted for by age or comorbidities. The mechanisms behind the high risk of mortality remain undetermined but are hypothesized to be related to the inflammatory status of frail patients.

Methods: In a prospective observational exploratory cohort study of hospitalized frail hip fracture patients, 92 inflammatory markers were tested in pre-operative serum samples and markers were tested against 6-month survival post-hip fracture surgery and incidence of acute kidney injury (AKI).

Serum levels of hydroxylated metabolites of arachidonic acid cross-sectionally and longitudinally predict knee pain progression: an observational cohort study.

Objective: To examine associations between serum oxylipins, which regulate tissue repair and pain signalling, and knee pain/radiographic osteoarthritis (OA) at baseline and knee pain at 3 year follow-up.

Method: Baseline, and 3 year follow-up, knee pain phenotypes were assessed from 154 participants in the Knee Pain in the Community (KPIC) cohort study. Serum and radiographic Kellgren and Lawrence (KL) and Nottingham line drawing atlas OA scores were collected at baseline.

The Effect of Acute Knee Injuries and Related Knee Surgery on Serum Levels of Pro- and Anti-inflammatory Lipid Mediators and Their Associations With Knee Symptoms.

Background: Despite an acute knee injury being a major risk factor for osteoarthritis, the factors that initiate and maintain this risk of longer-term knee symptoms are poorly understood. Bioactive lipids derived from omega-3 and -6 polyunsaturated fatty acids have key roles in the regulation of the inflammatory response and have been linked to joint damage and osteoarthritis pain in translational models.

Hypothesis: There would be associations between systemic levels of bioactive lipids and knee symptoms longitudinally after an acute knee injury and related knee surgery.

Bacteriophages, gut bacteria, and microbial pathways interplay in cardiometabolic health.

Cardiometabolic diseases are leading causes of mortality in Western countries. Well-established risk factors include host genetics, lifestyle, diet, and the gut microbiome. Moreover, gut bacterial communities and their activities can be altered by bacteriophages (also known simply as phages), bacteria-infecting viruses, making these biological entities key regulators of human cardiometabolic health.

Effect of a 2-week interruption in methotrexate treatment on COVID-19 vaccine response in people with immune-mediated inflammatory diseases (VROOM study): a randomised, open label, superiority trial.

Background: Methotrexate is the first-line treatment for immune-mediated inflammatory diseases and reduces vaccine-induced immunity. We evaluated if a 2-week interruption of methotrexate treatment immediately after COVID-19 booster vaccination improved antibody response against the S1 receptor binding domain (S1-RBD) of the SARS-CoV-2 spike protein and live SARS-CoV-2 neutralisation compared with uninterrupted treatment in patients with immune-mediated inflammatory diseases.

Method: We did a multicentre, open-label, parallel-group, randomised, superiority trial in secondary-care rheumatology and dermatology clinics in 26 hospitals in the UK.