Ectopic lymphoid-like structures often develop at sites of inflammation where they influence the course of infection, autoimmune disease, cancer and transplant rejection. These lymphoid aggregates ...range from tight clusters of B cells and T cells to highly organized structures that comprise functional germinal centres. Although the mechanisms governing ectopic lymphoid neogenesis in human pathology remain poorly defined, the presence of ectopic lymphoid-like structures within inflamed tissues has been linked to both protective and deleterious outcomes in patients. In this Review, we discuss investigations in both experimental model systems and patient cohorts to provide a perspective on the formation and functions of ectopic lymphoid-like structures in human pathology, with particular reference to the clinical implications and the potential for therapeutic targeting.
To evaluate the efficacy of remotely delivered motivational conversations on health outcomes in musculoskeletal populations.
Four electronic databases (inception-March 2022) were searched and ...combined with grey literature. Randomised control trials (RCTs) evaluating the effect of remotely delivered motivational conversation-based interventions within musculoskeletal populations, using valid measures of pain, disability, quality of life (QoL), or self-efficacy were included. Overall quality was assessed using GRADE criteria. Meta-analyses were performed using random effects models with pooled effect sizes expressed as standardised mean differences ( ± 95%CIs).
Twelve RCTs were included. Meta-analyses revealed very-low to moderate quality evidence that remote interventions have a positive effect on pain and disability both immediately post intervention and at long-term follow-up compared to control, and have a positive effect on self-efficacy immediately post intervention. There was no effect on QoL immediately post intervention or at long-term follow up.
Remotely delivered motivation-based conversational interventions have a positive effect on pain, disability, and self-efficacy but not on QoL.
Motivational conversations, delivered remotely, may be effective in improving some health-related outcomes in MSK populations. However, higher quality evidence is needed to determine optimal intervention durations, and dosing frequencies using sufficient sample sizes and follow-up time frames.
•Data is synthesised for remote delivery of motivation-based conversational interventions.•Twelve retained-trials investigated interventions in musculoskeletal populations.•Interventions had positive effects on pain, disability and self-efficacy.•Further research should examine differences in treatment modes and dosing.
There is a growing interest in the application of artificial intelligence (AI) to orthopaedic surgery. This review aims to identify and characterise research in this field, in order to understand the ...extent, range and nature of this work, and act as springboard to stimulate future studies. A scoping review, a form of structured evidence synthesis, was conducted to summarise the use of AI in orthopaedics. A literature search (1946-2019) identified 222 studies eligible for inclusion. These studies were predominantly small and retrospective. There has been significant growth in the number of papers published in the last three years, mainly from the USA (37%). The majority of research used AI for image interpretation (45%) or as a clinical decision tool (25%). Spine (43%), knee (23%) and hip (14%) were the regions of the body most commonly studied. The application of artificial intelligence to orthopaedics is growing. However, the scope of its use so far remains limited, both in terms of its possible clinical applications, and the sub-specialty areas of the body which have been studied. A standardized method of reporting AI studies would allow direct assessment and comparison. Prospective studies are required to validate AI tools for clinical use.
•Normal rising-to-walk (RTW) performance is fluid, but is non-fluid with pathology.•Rehabilitation could be tested if RTW controlled performance variables were known.•Consistent variables regardless ...of healthy RTW performance represent candidates.•In this review of 9 studies, no compelling evidence of consistency was found.•Studies designed to confirm consistent biomechanical variables are needed.
:The best approach to rehabilitate the control of everyday whole-body movement (e.g. rise-to-walk) after pathology remains unclear in part because the associated controlled performance variables are not known. Rise-to-walk can be performed fluidly (sit-to-walk) or non-fluidly (sit-to-stand, proceeded by gait-initiation). Biomechanical variables that remain consistent in health regardless of how rise-to walk is performed represent controlled performance variable candidates which could monitor rehabilitative change.
:To determine if any biomechanical parameters remain consistent across rising-to-walk (RTW) subtasks (sit-to-stand, gait-initiation, and sit-to-walk) in healthy adults for purposes of movement control assessment in clinical practice.
:Data sources included Medline, Cinahl, and Scopus databases, and the grey literature. Study selection was based on eligibility criteria and must have reported spatiotemporal, kinematic and/or kinetic biomechanical parameters featuring >1 RTW subtask. Data extraction and synthesis; standardised-mean-differences (SMDs) were calculated (pooled if replicated in >1 study) for each parameter. Consistency was determined if SMD95 %CIs included the zero-effect line.
:Nine studies (n = 99) were included (40 ± 7.5yrs). Seven parameters were replicated in >1 study and subjected to meta-analysis (fixed-effect model). Two were consistent between sit-to-stand and sit-to-walk: flexion-momentum time (M(95 %CI) = 0.055(-0.423 to 0.533); p = 0.823) and peak whole-body-centre-of-mass vertical velocity (M(95 %CI)= -0.415(-0.898 to 0.069); p = 0.093); and centre-of-pressure to whole-body-centre-of-mass distance at toe-off (M(95 %CI)= -0.137(-0.712 to 0.439); p = 0.642) between gait-initiation and sit-to-walk. Another 20 parameters were consistent based on single-study SMDs.
:Consistent parameters might exist across RTW subtasks. However, the evidence is based on few studies with small samples and variable RTW protocols. Future studies designed to confirm consistency using a standardised RTW protocol are needed.
Summary
Lymphoid neogenesis is traditionally viewed as a pre‐programmed process that promotes the formation of lymphoid organs during development. Here, the spatial organization of T and B cells in ...lymph nodes and spleen into discrete structures regulates antigen‐specific responses and adaptive immunity following immune challenge. However, lymphoid neogenesis is also triggered by chronic or persistent inflammation. Here, ectopic (or tertiary) lymphoid organs frequently develop in inflamed tissues as a response to infection, auto‐immunity, transplantation, cancer or environmental irritants. Although these structures affect local immune responses, the contribution of these lymphoid aggregates to the underlining pathology are highly context dependent and can elicit either protective or deleterious outcomes. Here we review the cellular and molecular mechanisms responsible for ectopic lymphoid neogenesis and consider the relevance of these structures in human disease.
The interrelationship between microtubules and the actin cytoskeleton in mechanoregulation of integrin-mediated adhesions is poorly understood. Here, we show that the effects of microtubules on two ...major types of cell-matrix adhesion, focal adhesions and podosomes, are mediated by KANK family proteins connecting the adhesion protein talin with microtubule tips. Both total microtubule disruption and microtubule uncoupling from adhesions by manipulations with KANKs trigger a massive assembly of myosin IIA filaments, augmenting focal adhesions and disrupting podosomes. Myosin IIA filaments are indispensable effectors in the microtubule-driven regulation of integrin-mediated adhesions. Myosin IIA filament assembly depends on Rho activation by the RhoGEF GEF-H1, which is trapped by microtubules when they are connected with integrin-mediated adhesions via KANK proteins but released after their disconnection. Thus, microtubule capture by integrin-mediated adhesions modulates the GEF-H1-dependent effect of microtubules on the assembly of myosin IIA filaments. Subsequent actomyosin reorganization then remodels the focal adhesions and podosomes, closing the regulatory loop.
Simulated historic near‐surface air temperature variations are often compared with observations of land air temperatures blended with sea surface temperatures. This study investigates claims that ...this is not a “true like‐with‐like” comparison, which may cause small biases in simulated twentieth century temperature changes, with implications for different climate attribution and projection studies. A more appropriate analysis, it is claimed, should use simulated sea surface temperatures blended with land air temperatures; an apparent discrepancy with observed trends is then reduced. As the temperature of the uppermost level in a model's ocean is used to represent simulated sea surface temperatures, that models have inconsistent ways of representing land, and that simulations have differing sea ice coverages, the claim of an idealised analysis approach is challenged. An examination of Coupled Model Intercomparison Project simulations, compared with an observational dataset of near‐surface temperatures, suggests there is a bias in simulated historic trends when upper‐ocean temperatures are used instead of marine air temperatures, but this bias is small compared to other model and observational uncertainties and the impact of analysis choices. The results indicate that it is generally appropriate to use global near‐surface air temperature diagnostics to compare simulated historic climate change with observed temperature changes. Alternative model diagnostics are not necessarily superior to those used in standard approaches, and the emphasis of model and observational discrepancies may be based on overconfident reasoning.
Analyses of historical climate change often compare simulated near‐surface air temperatures with observations of land air temperatures blended with sea surface temperatures. There have been claims that this is not a “true like‐with‐like” comparison, and allegedly more appropriate analyses could result in reductions in apparent discrepancies with observed trends. The impact of blending simulated air and ocean temperatures is small relative to model and observational uncertainties and, also given model inconsistencies, it is appropriate to use near‐surface air temperatures.
Objective
The American College of Rheumatology (ACR) 1990 fibromyalgia classification criteria are based on the presence of widespread pain and tenderness. In 2010, new criteria were proposed that ...focused more on multiple symptoms, and these criteria were later modified to require only self report of symptoms. The current study aimed to determine the population prevalence of fibromyalgia and to compare differences in prevalence using the alternative criteria.
Methods
A cross‐sectional survey was conducted. Questionnaires, including items on pain, symptoms, and rheumatologic diagnoses, were mailed to 4,600 adults in northeast Scotland. Participants who had chronic widespread pain or those who met the modified 2010 criteria, plus a subsample of other participants, were invited to attend a research clinic. Attendees completed an additional questionnaire and underwent a rheumatologic examination, and their signs and symptoms were classified according to the ACR 1990, 2010, and modified 2010 criteria. The prevalence of fibromyalgia according to each set of criteria was calculated, weighting back to the target population by age, sex, and area of residence.
Results
Of 1,604 questionnaire participants, 269 were invited to attend the research clinic, and 104 (39%) attended; 32 of these subjects (31%) met ≥1 set of fibromyalgia criteria. The prevalence of fibromyalgia according to the 1990, 2010, and modified 2010 criteria was 1.7% (95% confidence interval 95% CI 0.7–2.8), 1.2% (95% CI 0.3–2.1), and 5.4% (95% CI 4.7–6.1), respectively. The ratio of females to males was 13.7:1, 4.8:1, and 2.3:1 of those meeting the respective criteria sets.
Conclusion
Fibromyalgia prevalence varies with the different sets of classification criteria applied. In particular, prevalence is higher and a greater proportion of men are identified with the modified 2010 criteria as compared to the criteria sets requiring clinician input. This has important implications for the use of the new criteria, both in research and in clinical practice.