Biomarkers predictive of treatment response in psoriasis and psoriatic arthritis: a systematic review.

AimsThe ability to predict response to treatment remains a key unmet need in psoriatic disease. We conducted a systematic review of studies relating to biomarkers associated with response to treatment in either psoriasis vulgaris (PsV) or psoriatic arthritis (PsA).MethodsA search was conducted in PubMed, Embase and the Cochrane library from their inception to 2 September 2020, and conference proceedings from four major rheumatology conferences. Original research articles studying pre-treatment biomarker levels associated with subsequent response to pharmacologic treatment in either PsV or PsA were included.ResultsA total of 765 articles were retrieved and after review, 44 articles (22 relating to PsV and 22 to PsA) met the systematic review's eligibility criteria. One study examined the response to methotrexate, one the response to tofacitinib and all the other studies to biologic disease-modifying antirheumatic drugs (DMARDs). Whilst several studies examined the HLA-C*06 allele in PsV, the results were conflicting. Interleukin (IL)-12 serum levels and polymorphisms in the IL-12B gene show promise as biomarkers of treatment response in PsV. Most, but not all, studies found that higher baseline levels of C-reactive protein (CRP) were associated with a better clinical response to treatment in patients with PsA.ConclusionSeveral studies have identified biomarkers associated with subsequent response to treatment in psoriatic disease. However, due to the different types of biomarkers, treatments and outcome measures used, firm conclusions cannot be drawn. Further validation is needed before any of these biomarkers translate to clinical practice

Biomarkers predictive of treatment response in psoriasis and psoriatic arthritis: a systematic review.

AIMS: The ability to predict response to treatment remains a key unmet need in psoriatic disease. We conducted a systematic review of studies relating to biomarkers associated with response to treatment in either psoriasis vulgaris (PsV) or psoriatic arthritis (PsA). METHODS: A search was conducted in PubMed, Embase and the Cochrane library from their inception to 2 September 2020, and conference proceedings from four major rheumatology conferences. Original research articles studying pre-treatment biomarker levels associated with subsequent response to pharmacologic treatment in either PsV or PsA were included. RESULTS: A total of 765 articles were retrieved and after review, 44 articles (22 relating to PsV and 22 to PsA) met the systematic review's eligibility criteria. One study examined the response to methotrexate, one the response to tofacitinib and all the other studies to biologic disease-modifying antirheumatic drugs (DMARDs). Whilst several studies examined the HLA-C*06 allele in PsV, the results were conflicting. Interleukin (IL)-12 serum levels and polymorphisms in the IL-12B gene show promise as biomarkers of treatment response in PsV. Most, but not all, studies found that higher baseline levels of C-reactive protein (CRP) were associated with a better clinical response to treatment in patients with PsA. CONCLUSION: Several studies have identified biomarkers associated with subsequent response to treatment in psoriatic disease. However, due to the different types of biomarkers, treatments and outcome measures used, firm conclusions cannot be drawn. Further validation is needed before any of these biomarkers translate to clinical practice

The challenges of intersectionality: Researching difference in physical education

Researching the intersection of class, race, gender, sexuality and disability raises many issues for educational research. Indeed, Maynard (2002, 33) has recently argued that ‘difference is one of the most significant, yet unresolved, issues for feminist and social thinking at the beginning of the twentieth century’. This paper reviews some of the key imperatives of working with ‘intersectional theory’ and explores the extent to these debates are informing research around difference in education and Physical Education (PE). The first part of the paper highlights some key issues in theorising and researching intersectionality before moving on to consider how difference has been addressed within PE. The paper then considers three ongoing challenges of intersectionality – bodies and embodiment, politics and practice and empirical research. The paper argues for a continued focus on the specific context of PE within education for its contribution to these questions

Dopaminergic basis for signalling belief updates, but not surprise, and the link to paranoia

Distinguishing between meaningful and meaningless sensory information is fundamental to forming accurate representations of the world. Dopamine is thought to play a central role in processing the meaningful information content of observations, which motivates an agent to update their beliefs about the environment. However, direct evidence for dopamine’s role in human belief updating is lacking. We addressed this question in healthy volunteers who performed a model-based functional magnetic resonance imaging (fMRI) task designed to separate the neural processing of meaningful and meaningless sensory information. We modelled participant behaviour using a normative Bayesian observer model, and used the magnitude of the model-derived belief update following an observation to quantify its meaningful information content. We also acquired positron emission tomography (PET) imaging measures of dopamine function in the same subjects. We show that the magnitude of belief updates about task structure (meaningful information), but not pure sensory surprise (meaningless information), are encoded in midbrain and ventral striatum activity. Using PET we show that the neural encoding of meaningful information is negatively related to dopamine-2/3 receptor availability in the midbrain and dexamphetamine-induced dopamine release capacity in the striatum. Trial-by-trial analysis of task performance indicated that subclinical paranoid ideation is negatively related to behavioural sensitivity to observations carrying meaningful information about the task structure. The findings provide direct evidence implicating dopamine in model-based belief updating in humans, and have implications for understating the pathophysiology of psychotic disorders where dopamine function is disrupted

Genetic Diversity of Potassium Ion Channel Proteins Encoded by Chloroviruses That Infect Chlorella heliozoae

Chloroviruses are large, plaque-forming, dsDNA viruses that infect chlorella-like green algae that live in a symbiotic relationship with protists. Chloroviruses have genomes from 290 to 370 kb, and they encode as many as 400 proteins. One interesting feature of chloroviruses is that they encode a potassium ion (K+) channel protein named Kcv. The Kcv protein encoded by SAG chlorovirus ATCV-1 is one of the smallest known functional K+ channel proteins consisting of 82 amino acids. The KcvATCV-1 protein has similarities to the family of two transmembrane domain K+ channel proteins; it consists of two transmembrane -helixes with a pore region in the middle, making it an ideal model for studying K+ channels. To assess their genetic diversity, kcv genes were sequenced from 103 geographically distinct SAG chlorovirus isolates. Of the 103 kcv genes, there were 42 unique DNA sequences that translated into 26 new Kcv channels. The new predicted Kcv proteins differed from KcvATCV-1 by 1 to 55 amino acids. The most conserved region of the Kcv protein was the filter, the turret and the pore helix were fairly well conserved, and the outer and the inner transmembrane domains of the protein were the most variable. Two of the new predicted channels were shown to be functional K+ channels

Exercise and manual physiotherapy arthritis research trial (EMPART) for osteoarthritis of the hip: a multicenter randomized controlled trial.

OBJECTIVES: To determine the effectiveness of exercise therapy (ET) compared with ET with adjunctive manual therapy (MT) for people with hip osteoarthritis (OA); and to identify if immediate commencement of treatment (ET or ET+MT) was more beneficial than a 9-week waiting period for either intervention. DESIGN: Assessor-blind randomized controlled trial with a 9-week and 18-week follow-up. SETTING: Four academic teaching hospitals in Dublin, Ireland. PARTICIPANTS: Patients (N=131) with hip OA recruited from general practitioners, rheumatologists, orthopedic surgeons, and other hospital consultants were randomized to 1 of 3 groups: ET (n=45), ET+MT (n=43), and waitlist controls (n=43). INTERVENTIONS: Participants in both the ET and ET+MT groups received up to 8 treatments over 8 weeks. Control group participants were rerandomized into either ET or ET+MT groups after 9 week follow-up. Their data were pooled with original treatment group data: ET (n=66) and ET+MT (n=65). MAIN OUTCOME MEASURES: The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function (PF) subscale. Secondary outcomes included physical performance, pain severity, hip range of motion (ROM), anxiety/depression, quality of life, medication usage, patient-perceived change, and patient satisfaction. RESULTS: There was no significant difference in WOMAC PF between the ET (n=66) and ET+MT (n=65) groups at 9 weeks (mean difference, .09; 95% confidence interval [CI] -2.93 to 3.11) or 18 weeks (mean difference, .42; 95% CI, -4.41 to 5.25), or between other outcomes, except patient satisfaction with outcomes, which was higher in the ET+MT group (P=.02). Improvements in WOMAC, hip ROM, and patient-perceived change occurred in both treatment groups compared with the control group. CONCLUSIONS: Self-reported function, hip ROM, and patient-perceived improvement occurred after an 8-week program of ET for patients with OA of the hip. MT as an adjunct to exercise provided no further benefit, except for higher patient satisfaction with outcome

Remission in psoriatic arthritis: is it possible and how can it be predicted?

10.1186/ar3021Arthritis Research and Therapy123R9

Change in CD3 positive T-cell expression in psoriatic arthritis synovium correlates with change in DAS28 and magnetic resonance imaging synovitis scores following initiation of biologic therapy - a single centre, open-label study

With the development of increasing numbers of potential therapeutic agents in inflammatory disease comes the need for effective biomarkers to help screen for drug efficacy and optimal dosing regimens early in the clinical trial process. This need has been recognized by the Outcome Measures in Rheumatology Clinical Trials (OMERACT) group, which has established guidelines for biomarker validation. To seek a candidate synovial biomarker of treatment response in psoriatic arthritis (PsA), we determined whether changes in immunohistochemical markers of synovial inflammation correlate with changes in disease activity scores assessing 28 joints (ΔDAS28) or magnetic resonance imaging synovitis scores (ΔMRI) in patients with PsA treated with a biologic agent. Twenty-five consecutive patients with PsA underwent arthroscopic synovial biopsies and MRI scans of an inflamed knee joint at baseline and 12 weeks after starting treatment with either anakinra (first 10 patients) or etanercept (subsequent 15 patients) in two sequential studies of identical design. DAS28 scores were measured at both time points. Immunohistochemical staining for CD3, CD68 and Factor VIII (FVIII) was performed on synovial samples and scored by digital image analysis (DIA). MRI scans performed at baseline and at 12 weeks were scored for synovitis semi-quantitatively. The ΔDAS28 of the European League Against Rheumatism good response definition (>1.2) was chosen to divide patients into responder and non-responder groups. Differences between groups (Mann Whitney U test) and correlations between ΔDAS28 with change in immunohistochemical and MRI synovitis scores (Spearman's rho test) were calculated. Paired synovial samples and MRI scans were available for 21 patients (8 anakinra, 13 etanercept) and 23 patients (8 anakinra, 15 etanercept) respectively. Change in CD3 (ΔCD3) and CD68 expression in the synovial sublining layer (ΔCD68sl) was significantly greater in the disease responders compared to non-responders following treatment (P = 0.005 and 0.013 respectively). ΔCD3, but not ΔCD68 or ΔFVIII, correlated with both ΔDAS28 (r = 0.49, P = 0.025) and ΔMRI (r = 0.58, P = 0.009). The correlation of ΔCD3 with ΔDAS28 and ΔMRI following biologic treatment in this cohort contributes to the validation of ΔCD3 as a synovial biomarker of disease response in PsA, and supports the further evaluation of ΔCD3 for predictive properties of future clinical outcome