Clinical and Cellular Predictors of Outcomes in Autologous Conditioned Plasma Therapy for Knee Osteoarthritis: A Prospective Cohort Study

Introduction Autologous conditioned plasma (ACP) is a single-spin, leukocyte-poor platelet-rich plasma (PRP) that provides a plasma with a platelet concentration 2 to 3 times the blood platelet concentration. The objective of this study was to investigate the clinical effectiveness of ACP intra-articular injection in patients with knee osteoarthritis (OA) and to identify any demographic, disease-associated, or biological predictors of outcome. Methods A prospective cohort study was conducted between 2022 and 2023 in a single high-volume tertiary center, including 42 patients (54 knees) who consented to be enrolled. Patients underwent a series of 3 injections of ACP at weekly intervals, prepared using the Arthrex ACP Double-Syringe System. Lysholm scores were collected at baseline, 3-months, and 6-months post-injection. Results Forty patients (49 knees) completed the follow-up and were included in the final analysis. The mean age was 53.8 ± 10.16 years (range 35-76 years), and the median body mass index (BMI) was 29 (interquartile range [IQR]: 27-34). There were 22 females and 18 males. Treatment failure occurred in 12 out of 49 cases (24.49%). The mean platelet concentration in the ACP was 588.5 ± 183.2 × 10 6 /ml, with a mean platelet fold increase of 2.14 ± 0.71 compared to the baseline. Multi-linear regression modeling showed that older age and higher mean platelet concentration were predictors of higher post-injection Lysholm scores, with beta coefficients of 0.34 and 0.28, respectively, and p values of 0.013 and 0.036, respectively. Conclusion Autologous conditioned plasma provided clinical benefits in this cohort study of knee OA patients for at least 6 months post-injection. Older age and a higher mean platelet concentration in the ACP were identified as predictors of a higher Lysholm score

Feasibility and Acceptability of Online Culturally Adapted Cognitive Behavioural Therapy for Depression and Anxiety in Canadians of South Asian Origin: A Randomized Controlled Trial: Faisabilité et acceptabilité de la thérapie cognitivo-comportementale en ligne adaptée à la culture pour traiter la dépression et l'anxiété chez les Canadiens d'origine sud-asiatique : Essai contrôlé à répartition aléatoire.

BackgroundThis paper reports a pilot trial of culturally adapted CBT (CaCBT) for Canadian South Asians. The primary objective of this study was to assess the feasibility and acceptability of online CaCBT to treat anxiety and depression in Canadian South Asian individuals. The secondary objective was to measure changes in depression, anxiety, and disability.MethodsAn assessor-blind randomized clinical trial was conducted at 3 sites in Canada (Greater Toronto Area, Ottawa, and Vancouver). One hundred forty-six participants were randomly allocated to 1 of 2 groups: Ca-CBT (experimental group) or standard cognitive behavioural therapy (CBT) (control group) in a 1:1 ratio. The primary outcome, feasibility, was measured through engagement, recruitment, and participant retention. Acceptability was measured through the Verona Service Satisfaction Scale. Working Alliance Inventory was used to measure therapeutic engagement. Secondary outcomes included depression (Hospital Anxiety and Depression Scale-HADS), somatic symptoms (Bradford Somatic Inventory-BSI), and disability (WHO Disability Assessment Schedule 2.0 (WHODAS). Assessments were carried out at baseline, at the end of therapy (12 weeks from baseline), and at follow-up (36 weeks from baseline).ResultsWe were able to recruit participants within the given timeframe with excellent retention rates in both arms. Most participants in the intervention group, 56 (74.7%), attended ≥ 8 sessions, and 11 (14.7%) attended 5 to 7 sessions. Eight (10.7%) participants from the intervention group and 9 (12.0%) from the control group dropped out of therapy (<5 sessions). Participants in the intervention group reported higher levels of satisfaction (  = 0.001) and therapeutic engagement (  < 0.001) compared with the control group. Participants in both groups benefited from CBT.ConclusionsThis is the first report of online CaCBT for depression and anxiety for Canadian South Asians. The intervention is acceptable and feasible. Culturally adapted CBT is as effective as standard CBT in reducing the symptoms of depression and anxiety

Boundary Value Problems on a Star Thermal Graph and their Solutions

In this study, heat conductivity boundary value problems on a star graph are considered, inspired by engineering applications, e.g., heat conduction phenomena in mesh-like structures. Based on the generalized function method, a unified technique for solving boundary value problems on such graphs is developed. Generalized solutions to transient and stationary boundary value problems are constructed for different conditions at the end edges, with the Kirchhoff conditions at the common node. Regular integral representations of solutions to boundary value problems are obtained using the properties and symmetry of the fundamental solution’s Fourier transform. The derived results allow the action of various heat sources to be simulated, including concentrated ones by using singular generalized functions. The generalized function method enables a wide variety of boundary value problems to be tackled, including those with local boundary conditions at the ends of the graph, and various transmission conditions at the common node. Based on the research, the authors propose an analytical solution method under the action of various heat sources to solve various boundary value problems on a star thermal graph

Monitoring for 5-aminosalicylate nephrotoxicity in adults with inflammatory bowel disease: prognostic model development and validation using data from the Clinical Practice Research Datalink

Objective: To develop and validate a prognostic model for risk-stratified monitoring of 5-aminosalicylate nephrotoxicity. Methods: This UK retrospective cohort study used data from the Clinical Practice Research Datalink Aurum and Gold for model development and validation respectively. It included adults newly diagnosed with inflammatory bowel disease and established on 5-aminosalicylic acid (5-ASA) treatment between 1 January 2007 and 31 December 2019. Drug discontinuation associated with 5-ASA nephrotoxicity defined as a prescription gap of ≥90 days with decline in kidney function was the outcome. Patients prescribed 5-ASAs for ≥6 months were followed-up for up to 5 years. Penalised Cox regression was used to develop the risk equation with bootstrapping for internal validation and optimism adjustment. Model performance was assessed in terms of calibration and discrimination. Results: 13 728 and 7318 participants who contributed 40 378 and 20 679 person-years follow-up formed the development and validation cohorts with 170 (1.2%) and 98 (1.3%) outcome events respectively. Nine predictors were included in the final model, including chronic kidney disease stage 3 and hazardous alcohol use as strong predictors. Age and Body Mass Index were weak predictors. The optimism-adjusted calibration slope, C and D statistics in the development and validation data were 0.90, 0.64 and 0.98, and 1.01, 0.66 and 0.94 respectively. Conclusion: This prognostic model used information from routine clinical care and performed well in an independent validation cohort. It can be used to risk-stratify blood test monitoring during established 5-ASA treatment. A key limitation is that the decline in kidney function could have been due to factors other than 5-ASA nephrotoxicity

Pharmacological pain management in patients with rheumatoid arthritis: a narrative literature review

Background: Pain is a major challenge for patients with rheumatoid arthritis (RA), with many people suffering chronic pain. Current RA management guidelines focus on assessing and reducing disease activity using disease-modifying anti-rheumatic drugs (DMARDs). Consequently, pain care is often suboptimal, with growing evidence that analgesics are widely prescribed to patients with RA, despite potential toxicities and limited evidence for efficacy. Our review provides an overview of pharmacological treatments for pain in patients with RA, summarising their efficacy and use. Findings: Thirteen systematic reviews of drug efficacy for pain in patients with RA were included in this review. These showed moderate- to high-quality evidence from clinical trials in more contemporary time-periods (mainly 1990s/2000s for synthetic DMARDs and post-2000 for biological/targeted synthetic DMARDs) that, in patients with active RA, short-term glucocorticoids and synthetic, biologic, and targeted synthetic DMARDs have efficacy at reducing pain intensity relative to placebo. In contrast, they showed low-quality evidence from trials in more historical time-periods (mainly in the 1960s–1990s for opioids and paracetamol) that (aside from naproxen) analgesics/neuromodulators provide any improvements in pain relative to placebo, and no supportive evidence for gabapentinoids, or long-term opioids. Despite this evidence base, 21 studies of analgesic prescribing in patients with RA consistently showed substantial and sustained prescribing of analgesics, particularly opioids, with approximately one quarter and > 40% of patients receiving chronic opioid prescriptions in each year in England and North America, respectively. Whilst NSAID prescribing had fallen over time across countries, gabapentinoid prescribing in England had risen from < 1% of patients in 2004 to approximately 10% in 2020. Prescribing levels varied substantially between individual clinicians and groups of patients. Conclusions: In patients with active RA, DMARDs have efficacy at reducing pain, supporting the role of treat-to-target strategies. Despite limited evidence that analgesics improve pain in patients with RA, these medicines are widely prescribed. The reasons for this are unclear. We consider that closing this evidence-to-practice gap requires qualitative research exploring the drivers of this practice, high-quality trials of analgesic efficacy in contemporary RA populations, alongside an increased focus on pain management (including pharmacological and non-pharmacological options) within RA guidelines

Learning from online hate speech and digital racism: From automated to diffractive methods in social media analysis

There has been a dramatic surge in uses of big data analytics and automated methods to detect and remove hate speech from social media, with these methods deployed both by platforms themselves and within academic research. At the same time, recent social scientific scholarship has accused social media data analytics of decontextualizing complex sociological issues and reducing them to linguistic problems that can be straightforwardly mapped and removed. Intervening in these debates, this article draws on findings from two interdisciplinary projects, spanning five years in total, which generated comparative datasets from Twitter (X). Focusing on three issues that we identified and negotiated in our own analysis – which we characterize as problems of context, classification and reproducibility – we build on existing critiques of automated methods, while also charting methodological pathways forward. Informed by theoretical debates in feminist science studies and STS, we set out a diffractive approach to engaging with large datasets from social media, which centralizes tensions rather than correlations between computational, quantitative and qualitative data

An old spice with new tricks: Curcumin targets adenoma and colorectal cancer stem-like cells associated with poor survival outcomes.

The cost of cancer care globally is unsustainable and strategies to reduce the mounting burden of cancer are urgently needed. One approach is the use of preventive therapies to reduce cancer risk; dietary-derived compounds with good safety profiles represent a promising source of potential candidates but translating encouraging preclinical data to successful trials presents significant challenges. Development of curcumin, from the spice turmeric, as a preventive therapy for colorectal cancer (CRC) is hindered by poor understanding of its mechanism of action. Using patient derived xenografts and ex-vivo 3D-models exposed to clinically achievable curcumin concentrations, we found that it targets proliferating cancer stem-like cells (CSCs) within premalignant adenoma and early-stage cancer tissues, with broad spectrum activity across all molecular subtypes. Transcriptomics analysis revealed that curcumin pushes CSCs towards differentiation over self-renewal, thereby inhibiting tumour development. Evidence suggests these effects involve direct protein binding of curcumin to NANOG, a master regulator of CRC CSCs, and impairment of its transcriptional activity via direct interference with NANOG-DNA binding. Furthermore, curcumin decreased the proportion of proliferating CSCs, defined by NANOG/Ki67 co-expression in patient derived explants and individuals with tumours containing a small fraction of these cells had greatly improved progression-free survival compared to those in the highest quartile for expression. The use of curcumin to minimise this cellular population may yield significant benefit and its clinical evaluation is warranted. Overall, this study provides crucial mechanistic insight, identifying patient populations likely to benefit from curcumin for prevention of sporadic CRC and theragnostic biomarkers for assessing efficacy. [Abstract copyright: Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.

A humanised thrombus-on-a-chip model utilising tissue-engineered arterial constructs: A method to reduce and replace mice used in thrombosis and haemostasis research.

The study of in vivo thrombus formation has principally been performed using intravital microscopy in mice and other species. These have allowed us to visualise the molecular and cellular processes that regulate thrombus formation inside the body. However current in vivo arterial thrombosis models are difficult to standardise between labs and frequently produce results that do not reliably translate successfully in human clinical trials. Here we provide a step-by-step description with accompanying video tutorials to demonstrate how to produce a 3D humanised thrombus-on-a-chip model, which uses perfusion of fluorescently-labelled human blood over a mechanically-injured human tissue engineered arterial construct (TEAC) within a 3D printed microfluidic flow chamber to replicate thrombus formation within a healthy artery. We also provide a written methodology on how to use 3D printing to produce a mechanical injury press that can reproducibly damage the TEAC as a stimulus for thrombus formation as part of a mechanical injury model. Perfusion of the uninjured TEAC with whole human blood containing DiOC6-labelled platelets without initiating notable thrombus formation. The mechanical injury press was shown to induce a reproducible puncture wound in the TEAC. Fluorescence microscopy was used to demonstrate that thrombus formation could be observed reproducibly around sites of injury. This humanised thrombosis-on-a-chip model can replace the use of animals in in vivo thrombosis models for preclinical assessment of anti-thrombotic therapies. This method also offers multiple scientific advantages: allowing new drugs to be directly tested on human blood from a diverse array of donors, facilitating use of a realistic and reproducible injury modality as well as removing the potential confounding effects of general anaesthetics in animal studies. The use of human thrombus-on-a-chip models combining TEACs offers a new methodology to reduce animal use whilst improving the predictive capabilities of preclinical trials of anti-thrombotic therapies

Exercising an individualized process of agency in restoring a self and repairing a daily life disrupted by fibromyalgia: A narrative analysis

Objective: Fibromyalgia is a chronic condition that has major impact on people’s lives. This study examines individuals’ illness trajectories, with a particular focus on daily life experiences and self-managing.Methods: Narrative interviews were conducted, asking participants to story their daily life experiences from illness onset to the present, and to reflect on the future. Embedded in their storying were experiences of recently being diagnosed, navigating daily life in the face of illness, and participating in a self-management intervention. The data underwent a narrative analysis.Results: In keeping with the idiographic focus of narrative research, two individuals’ stories were chosen to portray an individualized process of self-managing illness in daily life. The storylines ‘Resuming prior self and life’ and ‘Taking life and self in new direction’ illuminate how individuals with differing illness trajectories and life situations autonomously apply resources available to them in their lives. They make sense of illness by bringing together their own lifeworld experiences of stress and factual knowledge and, through a process of individual agency, discover and try out what is right to do in their own life in the face of chronic illness.Conclusions: These two storylines illustrate that a self-managing process is an individual process nested in the person’s social context. Self-management encompasses an individualized process of agency in remaking daily life and reconstructing a sense of self

Association of air pollution from a landfill site with changes in primary care consultation patterns

Background: Waste landfill sites are associated with gaseous emissions and this air pollution can cause unpleasant smells (“malodour”). This causes concerns about its impact on the health of the local population. This study assessed change in general practice consultation behaviour during a period of increased complaints associated with air pollution at a UK landfill site. Methods: The study period was October 2020 to December 2021. The age-sex standardised prevalence and incidence of consultations for mental health, respiratory, and other symptoms hypothesised to be impacted by the air pollution issues were determined and compared between: (i) 6 practices located close to the landfill site (zone A), (ii) 6 practices located a mid-distance from the site (zone B), (iii) 6 practices located further away and expected to have had less impact (zone C). Results: There was an increased consultation for mental health problems in practices nearest to the landfill site compared to those furthest away, however, consultation frequencies for respiratory and other potentially associated symptoms were lower and likelihood of consultation was consistently highest in practices located in zone B. Conclusion: This study showed limited evidence of an increase in recorded primary healthcare contacts for conditions and symptoms hypothesised to be connected to air pollution. It highlighted the challenges of examining impact of air pollution on the health of local populations. Since this study focussed on coded consultations in primary care and not symptoms present in the general population, an impact on the health of individuals cannot be ruled out