Treatment of frozen shoulder with subcutaneous TNF-alpha blockade compared with local glucocorticoid injection: a randomised pilot study

We compared the effect of subcutaneous adalimumab injections with intraarticular glucocorticoid injections on frozen shoulder of 18 patients with unilateral joint involvement. Ten patients were randomised to subcutaneous injections with adalimumab and eight to intraarticular glucocorticoid injections administered every other week for a total of three administrations. The evaluation included validated scores. No effect of subcutaneous injections of adalimumab on frozen shoulder symptoms was demonstrated.     

The effect of rater training on scoring performance and scale-specific expertise amongst occupational therapists participating in a multicentre study: a single-group pre–post-test study

Purpose: In order to enhance the quality of the data collected in a multicentre validation study of a revised Danish version of the McGill Ingestive Skills Assessment (MISA), the authors developed a rater training programme. The purpose of the present study was to evaluate the effect of the training on scoring performance and scale-specific expertise amongst raters. Method: During 2 days of rater training, 81 occupational therapists (OTs) were qualified to observe and score dysphagic clients’ mealtime performance according to the criteria of 36 MISA-items. The training effects were evaluated pre- to post-training using percentage exact agreement (PA) of scored MISA items of a case-vignette and a Likert scale self-report of scale-specific expertise. Results: PA increased significantly from pre- to post-training (Z = ?4.404, p < 0.001), although items for which the case-vignette reflected deficient mealtime performance appeared most difficult to score. The OTs scale-specific expertise improved significantly (knowledge: Z = ?7.857, p < 0.001 and confidence: Z = ?7.838, p < 0.001). Conclusion: Rater training improved OTs scoring performance when using the Danish MISA as well as their perceived scale-specific expertise. Future rater training should emphasis the items identified as those most difficult to score. Additionally, further studies addressing different training approaches and durations are warranted.

• Implications for Rehabilitation

• When occupational therapists (OTs) use the McGill Ingestive Skills Assessment (MISA) they observe, interpret and record occupational performance of dysphagic clients participating in a meal. This is a highly complex task, which might introduce unwanted variability in measurement scores.

• A 2-day rater training programme was developed and this builds on the findings of several studies. These suggest that combinations of different training methods tend to yield the most effective results.

• Participation in the newly developed training programme on how to administer the MISA significantly reduces unwanted variability in measurement scores and improves OTs’ competency.

• The training programme could be used in undergraduate and postgraduate dysphagia education initiatives to help OTs understanding of the content and the scoring criteria for each aspect of occupational performance during a meal, thus developing observation skills as well as recognizing and avoiding the most common errors in measurement scores.

     

Ficolin-2 recognizes DNA and participates in the clearance of dying host cells

Ficolin-2 is a serum opsonin, which has been shown to be a pattern recognition molecule in the lectin complement activation pathway. Because innate immune mechanisms are involved in maintaining tissue homeostasis we hypothesized that Ficolin-2 also participate in the clearance of dying host cells. We found that Ficolin-2 binds to late apoptotic cells, as well as to apoptotic bodies and necrotic cells, but not to early apoptotic cells. We demonstrated that Ficolin-2 binds DNA in a calcium dependent manner and that DNA inhibits the binding to late apoptotic and necrotic cells, suggesting that DNA on permeable dying cells is a plausible ligand. Reconstituting serum deficient of Ficolin-2, C1q and mannose-binding lectin with Ficolin-2 augmented deposition of complement C4 on necrotic cells. Opsonization leads to an enhanced attachment/uptake of necrotic cells by macrophages. In conclusion dying host cells expose ligands with the capacity of binding Ficolin-2, which in turn leads to increased attachment and engulfment. Binding of Ficolin-2 to DNA points at nucleic acid exposed by permeable late apoptotic and necrotic cells as one of the ligands for Ficolin-2. Ficolin-2 may therefore be a scavenger molecule participating in the removal of host cells and maintenance of tissue homeostasis.     

Trained immunity in organ transplantation

Consistent induction of donor‐specific unresponsiveness in the absence of continuous immunosuppressive therapy and toxic effects remains a difficult task in clinical organ transplantation. Transplant immunologists have developed numerous experimental treatments that target antigen‐presentation (signal 1), costimulation (signal 2), and cytokine production (signal 3) to establish transplantation tolerance. While promising results have been obtained using therapeutic approaches that predominantly target the adaptive immune response, the long‐term graft survival rates remain suboptimal. This suggests the existence of unrecognized allograft rejection mechanisms that contribute to organ failure. We postulate that trained immunity stimulatory pathways are critical to the immune response that mediates graft loss. Trained immunity is a recently discovered functional program of the innate immune system, which is characterized by nonpermanent epigenetic and metabolic reprogramming of macrophages. Since trained macrophages upregulate costimulatory molecules (signal 2) and produce pro‐inflammatory cytokines (signal 3), they contribute to potent graft reactive immune responses and organ transplant rejection. In this review, we summarize the detrimental effects of trained immunity in the context of organ transplantation and describe pathways that induce macrophage training associated with graft rejection.     

Optical mechanisms regulating emmetropisation and refractive errors: evidence from animal models

Our current understanding of emmetropisation and myopia development has evolved from decades of work in various animal models, including chicks, non-human primates, tree shrews, guinea pigs, and mice. Extensive research on optical, biochemical, and environmental mechanisms contributing to refractive error development in animal models has provided insights into eye growth in humans. Importantly, animal models have taught us that eye growth is locally controlled within the eye, and can be influenced by the visual environment. This review will focus on information gained from animal studies regarding the role of optical mechanisms in guiding eye growth, and how these investigations have inspired studies in humans. We will first discuss how researchers came to understand that emmetropisation is guided by visual feedback, and how this can be manipulated by form-deprivation and lens-induced defocus to induce refractive errors in animal models. We will then discuss various aspects of accommodation that have been implicated in refractive error development, including accommodative microfluctuations and accommodative lag. Next, the impact of higher order aberrations and peripheral defocus will be discussed. Lastly, recent evidence suggesting that the spectral and temporal properties of light influence eye growth, and how this might be leveraged to treat myopia in children, will be presented. Taken together, these findings from animal models have significantly advanced our knowledge about the optical mechanisms contributing to eye growth in humans, and will continue to contribute to the development of novel and effective treatment options for slowing myopia progression in children.