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Oxidized LDL accelerates cartilage destruction and inflammatory chondrocyte death in osteoarthritis by disrupting the TFEB-regulated autophagy-lysosome pathway
No full textOsteoarthritis (OA) involves cartilage degeneration, thereby causing inflammation and pain. Cardiovascular diseases, such as dyslipidemia, are risk factors for OA; however, the mechanism is unclear. We investigated the effect of dyslipidemia on the development of OA. Treatment of cartilage cells with low-density lipoprotein (LDL) enhanced abnormal autophagy but suppressed normal autophagy and reduced the activity of transcription factor EB (TFEB), which is important for the function of lysosomes. Treatment of LDL-exposed chondrocytes with rapamycin, which activates TFEB, restored normal autophagy. Also, LDL enhanced the inflammatory death of chondrocytes, an effect reversed by rapamycin. In an animal model of hyperlipidemia-associated OA, dyslipidemia accelerated the development of OA, an effect reversed by treatment with a statin, an anti-dyslipidemia drug, or rapamycin, which activates TFEB. Dyslipidemia reduced the autophagic flux and induced necroptosis in the cartilage tissue of patients with OA. The levels of triglycerides, LDL, and total cholesterol were increased in patients with OA compared to those without OA. The C-reactive protein level of patients with dyslipidemia was higher than that of those without dyslipidemia after total knee replacement arthroplasty. In conclusion, oxidized LDL, an important risk factor of dyslipidemia, inhibited the activity of TFEB and reduced the autophagic flux, thereby inducing necroptosis in chondrocytes
Open mic poetry performance
No full textSpoken word performance development is part of my practice.
Open Mic at Poco Loco in Chatham, Medway. Testing some of my new work with a non-black audienc
Evidence for exercise-based interventions across 45 different long-term conditions: An overview of systematic reviews
Get PDFBackground
Almost half of the global population face significant challenges from long-term conditions (LTCs) resulting in substantive health and socioeconomic burden. Exercise is a potentially key intervention in effective LTC management.
Methods
In this overview of systematic reviews (SRs), we searched six electronic databases from January 2000 to October 2023 for SRs assessing health outcomes (mortality, hospitalisation, exercise capacity, disability, frailty, health-related quality of life (HRQoL), and physical activity) related to exercise-based interventions in adults (aged >18 years) diagnosed with one of 45 LTCs. Methodological quality was assessed using AMSTAR-2. International Prospective Resister of Systematic Reviews (PROSPERO) ID: CRD42022319214.
Findings
Forty-two SRs plus three supplementary RCTs were included, providing 990 RCTs in 936,825 people across 39 LTCs. No evidence was identified for six LTCs. Predominant outcome domains were HRQoL (82% of SRs/RCTs) and exercise capacity (66%); whereas disability, mortality, physical activity, and hospitalisation were less frequently reported (≤25%). Evidence supporting exercise-based interventions was identified in 25 LTCs, was unclear for 13 LTCs, and for one LTC suggested no effect. No SRs considered multimorbidity in the delivery of exercise. Methodological quality varied: critically-low (33%), low (26%), moderate (26%), and high (12%).
Interpretation
Exercise-based interventions improve HRQoL and exercise capacity across numerous LTCs. Key evidence gaps included limited mortality and hospitalisation data and consideration of multimorbidity impact on exercise-based interventions.
Funding
This study was funded by the National Institute for Health and Care Research (NIHR; Personalised Exercise-Rehabilitation FOR people with Multiple long-term conditions (multimorbidity)—NIHR202020)
An initial evaluation of an online, compassionate intervention for adults with type 1 and type 2 Diabetes Mellitus
Get PDFBackground: Individuals with a Chronic Physical Health Condition (CPHC) may experience ongoing challenges with physical and psychological wellbeing. Psychological therapies are offered to this population and literature is emerging to indicate that compassion-focused interventions may be useful. This review sought to assess the evidence-base for the effectiveness and acceptability of digital, self-compassion interventions for individuals with CPHCs.
Methods: A quantitative, systematic review of five databases (four published, one unpublished) elicited 12 studies that met inclusion criteria. Studies were assessed for quality using the Effective Public Healthcare Practice Project tool. Data was extracted and narratively synthesised.
Results: Included studies were of a weak (n=7) or moderate quality (n=5), with samples of chronic pain, visible skin conditions, breast cancer survivors, type two diabetes mellitus, coeliac disease and mixed CPHC populations. Findings suggested preliminary evidence for the effectiveness and acceptability of digital, self-compassion interventions in CPHCs, particularly in people with chronic pain and breast cancer survivors. This was reflected in the change of self-compassion, psychological and condition-specific outcome measures, along with reported satisfaction and adherence
Discussion: Given the preliminary findings, digital, self-compassion interventions appear to be effective and acceptable for some CPHCs. Suggestions for future research have been made in the context of the reported strengths and limitations of this systematic review
Positioning and authenticity in data collection: researching racism in education contexts
No full textThis study examines the challenges of researching one of the most sensitive topics in education contexts: racism. Based on a research project which critically examined the culture in a UK university, data were collected using participant observation and in-depth interviews with participants from an underrepresented group. They were then analysed using Interpretative Phenomenological Analysis (IPA). In this study, we show how approaching a case study from both an emic and etic perspective by flexibly positioning oneself as both an insider and outsider can play a significant role in gaining access to the studied group and producing rich, authentic data. We show how, if treated rigorously and responsibly, research can successfully undertake a range of critical tasks: providing a platform for marginalised participants in a complex social context; establishing a voice which both amplifies these marginalised perspectives and communicates challenging messages to a wider audience; challenging and renewing critical concepts that can both illuminate complex, qualitative findings and provide conceptual tools for further research
Defining criteria for disease activity states in systemic juvenile idiopathic arthritis based on the systemic Juvenile Arthritis Disease Activity Score
Get PDFObjective
To develop and validate cutoff values in the systemic Juvenile Arthritis Disease Activity Score 10 (sJADAS10) that distinguish the states of inactive disease (ID), minimal disease activity (MiDA), moderate disease activity (MoDA), and high disease activity (HDA) in children with systemic juvenile idiopathic arthritis (sJIA), based on subjective disease state assessment by the treating pediatric rheumatologist.
Methods
The cutoffs definition cohort was composed of 400 patients enrolled at 30 pediatric rheumatology centers in 11 countries. Using the subjective physician rating as an external criterion, 6 methods were applied to identify the cutoffs: mapping, calculation of percentiles of cumulative score distribution, Youden index, 90% specificity, maximum agreement, and ROC curve analysis. Sixty percent of the patients were assigned to the definition cohort and 40% to the validation cohort. Cutoff validation was conducted by assessing discriminative ability.
Results
The sJADAS10 cutoffs that separated ID from MiDA, MiDA from MoDA, and MoDA from HDA were ≤ 2.9, ≤ 10, and > 20.6. The cutoffs discriminated strongly among different levels of pain, between patients with or without morning stiffness, and between patients whose parents judged their disease status as remission or persistent activity/flare or were satisfied or not satisfied with current illness outcome.
Conclusion
The sJADAS cutoffs revealed good metrologic properties in both definition and validation cohorts, and are therefore suitable for use in clinical trials and routine practice
Primary school mentalisation-based art therapy (Primary-smART): a Person-based approach optimisation study
No full textBackground
The children’s mental health crisis in the UK continues to worsen and more and more schools are employing art therapists (ATs) to provide services for children experiencing social, emotional, and mental health (SEMH) difficulties. Although some studies have found indications of positive SEMH outcomes following art therapy, the evidence-base is still emerging. The initial development of a formalised art therapy intervention called Primary-smART included children, teachers, parents/carers, and art therapists. Indications from exploratory research showed this intervention could be helpful for children experiencing SEMH difficulties.
Aims
This study aimed to optimise a Primary-smART toolkit to ensure it is acceptable, engaging and persuasive for ATs in preparation for a future evaluation study in primary schools with children.
Methods
The Person-Based Approach (PBA) to intervention development was used to develop Primary-smART. In this study, feedback gained through online interviews with ATs was used to refine and optimise the toolkit.
Results
The 18 ATs who participated in this study perceived Primary-smART as acceptable overall. However, ATs during Rounds 1, 2, and 3 had important concerns which may have resulted in barriers to using Primary-smART. Seven out of eight main sections were modified and no new significant barriers were fed back by Round 4.
Conclusions
This study was successful in refining and optimising the Primary-smART toolkit. Results show that PBA methods enabled the research team to meet the study's aims.
Implications for practice/policy/future research
Future evaluation studies are now needed to test the clinical, carbon and cost effectiveness of Primary-smART