Tangled terminology: what's in a name?

Ann Clark and colleagues from the SLI in Scotland SIG Committee look at the use of terminology to describe the needs of children they supportcaslpub3239pu

3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine

Tryptophan catabolism is a major metabolic pathway utilized by several professional and non-professional antigen presenting cells to maintain immunological tolerance. Here we report that 3-hydroxy-l-kynurenamine (3-HKA) is a biogenic amine produced via an alternative pathway of tryptophan metabolism. In vitro, 3-HKA has an anti-inflammatory profile by inhibiting the IFN-gamma mediated STAT1/NF-kappa Beta pathway in both mouse and human dendritic cells (DCs) with a consequent decrease in the release of pro-inflammatory chemokines and cytokines, most notably TNF, IL-6, and IL12p70. 3-HKA has protective effects in an experimental mouse model of psoriasis by decreasing skin thickness, erythema, scaling and fissuring, reducing TNF, IL-1 beta, IFN-gamma, and IL-17 production, and inhibiting generation of effector CD8(+) T cells. Similarly, in a mouse model of nephrotoxic nephritis, besides reducing inflammatory cytokines, 3-HKA improves proteinuria and serum urea nitrogen, overall ameliorating immune-mediated glomerulonephritis and renal dysfunction. Overall, we propose that this biogenic amine is a crucial component of tryptophan-mediated immune tolerance. 3-hydroxy-L-kynurenamine (3-HKA) is a metabolite deriving from a lateral pathway of tryptophan catabolism. Here the authors identify 3-HKA as a biogenic amine and show it has anti-inflammatory properties that can protect mice against psoriasis and nephrotoxic nephritis.Peer reviewe

The PIKfyve Inhibitor YM201636 Blocks the Continuous Recycling of the Tight Junction Proteins Claudin-1 and Claudin-2 in MDCK cells

Tight junctions mediate the intercellular diffusion barrier found in epithelial tissues but they are not static complexes; instead there is rapid movement of individual proteins within the junctions. In addition some tight junction proteins are continuously being endocytosed and recycled back to the plasma membrane. Understanding the dynamic behaviour of tight junctions is important as they are altered in a range of pathological conditions including cancer and inflammatory bowel disease. In this study we investigate the effect of treating epithelial cells with a small molecule inhibitor (YM201636) of the lipid kinase PIKfyve, a protein which is involved in endocytic trafficking. We show that MDCK cells treated with YM201636 accumulate the tight junction protein claudin-1 intracellularly. In contrast YM201636 did not alter the localization of other junction proteins including ZO-1, occludin and E-cadherin. A biochemical trafficking assay was used to show that YM201636 inhibited the endocytic recycling of claudin-1, providing an explanation for the intracellular accumulation. Claudin-2 was also found to constantly recycle in confluent MDCK cells and treatment with YM201636 blocked this recycling and caused accumulation of intracellular claudin-2. However, claudin-4 showed negligible endocytosis and no detectable intracellular accumulation occurred following treatment with YM201636, suggesting that not all claudins show the same rate of endocytic trafficking. Finally, we show that, consistent with the defects in claudin trafficking, incubation with YM201636 delayed formation of the epithelial permeability barrier. Therefore, YM201636 treatment blocks the continuous recycling of claudin-1/claudin-2 and delays epithelial barrier formation

Asymmetry during functional movement screening and injury risk in junior football players : a replication study

An indicator of movement quality and potential injury risk during Functional Movement Screen (FMS) testing is the presence of asymmetry when comparing the left and right sides of the body. The aim of the study was to investigate the reproducibility of the injury risk model proposed in our previous research (Chalmers et al. 2017; derivation study) that showed an increased injury risk for elite junior Australian football players demonstrating ≥2 asymmetrical FMS subtests. We used a direct replication design. Players underwent pre-season FMS testing, and an injury surveillance system monitored 277 male participants during the subsequent regular season competition. Designated club officials monitored the weekly competition participation of players. The definition of an injury was "a trauma or medical condition which caused a player to miss a competitive game". Cox proportional hazards regression models were used to investigate the relationship between asymmetry and number of games played before first injury (ie, survival time). The level of reproducibility was determined according to statistical significance, effect size, and subjective assessment. Demonstrating asymmetry during FMS testing was not associated with a significant increase in prospective injury risk in the replication study (P > .05). Moreover, effect sizes (hazard ratios) from the derivation dataset were not within the 95% confidence intervals of the respective asymmetry predictor in the replication dataset. Subjectively, researchers were in agreement that the findings from the derivation data were not successfully reproduced. Clinicians and researchers should be cautious about using FMS asymmetry findings to derive injury risk for junior football players

High prevalence of dysfunctional, asymmetrical, and painful movement in elite junior Australian Football players assessed using the Functional Movement Screen

Objectives: The purpose of this study was to describe the prevalence of dysfunctional, asymmetrical, and painful movement in junior Australian Football players using the Functional Movement Screen (FMS). Design: Cross-sectional study. Methods: Elite junior male Australian Football players (n = 301) aged 15-18 years completed pre-season FMS testing. The FMS consists of 7 sub-tests: deep squat, hurdle step, in-line lunge, shoulder mobility, active straight leg raise, trunk stability push-up (TSPU) and rotary stability. The shoulder mobility, TSPU, and rotary stability tests were combined with an accompanying clearing test to assess pain. Each sub-test was scored on an ordinal scale from 0 to 3 and summed to give a composite score out of 21. Composite scores ≤14 were operationally defined as indicating dysfunctional movement. Players scoring differently on left and right sides were considered asymmetrical. Players reported whether they missed any games due to injury in the preceding 22 game season. Results: Sixty percent of players (n = 182) had composite scores ≤14, 65% of players (n = 196) had at least one asymmetrical sub-test, and 38% of players (n = 113) had at least one painful sub-test. Forty-two percent of players (n = 126) missed at least one game in the previous season due to injury. Previous injury did not influence composite score (p = 0.951) or asymmetry (p = 0.629). Players reporting an injury during the previous season were more likely to experience pain during FMS testing (odds ratio 1.97, 95% confidence interval 1.23-3.18; . p = 0.005). Conclusions: Junior Australian Football players demonstrate a high prevalence of dysfunctional, asymmetrical, and painful movement during FMS testing.5 page(s

High prevalence of dysfunctional, asymmetrical, and painful movement in elite junior Australian Football players assessed using the Functional Movement Screen

Objectives. The purpose of this study was to describe the prevalence of dysfunctional, asymmetrical, and painful movement in junior Australian Football players using the Functional Movement Screen (FMS). Design. Cross-sectional study. Methods. Elite junior male Australian Football players (n = 301) aged 15-18 years completed pre-season FMS testing. The FMS consists of 7 sub-tests: deep squat, hurdle step, in-line lunge, shoulder mobility, active straight leg raise, trunk stability push-up (TSPU) and rotary stability. The shoulder mobility, TSPU, and rotary stability tests were combined with an accompanying clearing test to assess pain. Each sub-test was scored on an ordinal scale from 0-3 and summed to give a composite score out of 21. Composite scores ≤14 were operationally defined as indicating dysfunctional movement. Players scoring differently on left and right sides were considered asymmetrical. Players reported whether they missed any games due to injury in the preceding 22 game season. Results. Sixty percent of players (n = 182) had composite scores ≤14, 65% of players (n = 196) had at least one asymmetrical sub-test, and 38% of players (n = 113) had at least one painful sub-test. Forty-two percent of players (n = 126) missed at least one game in the previous season due to injury. Previous injury did not influence composite score (p = 0.951) or asymmetry (p = 0.629). Players reporting an injury during the previous season were more likely to experience pain during FMS testing (odds ratio 1.97, 95% confidence interval 1.23 to 3.18; p = 0.005)

Asymmetry during preseason Functional Movement Screen testing is associated with injury during a junior Australian football season

Objectives: The Functional Movement Screen (FMS) is a popular screening tool, however, the postulated relationship between prospective injury and FMS scoring remains sparsely explored in adolescent athletes. The aim of the study was to examine the association between pre-season FMS scores and injuries sustained during one regular season competition in elite adolescent Australian football players. Design: Prospective cohort study. Methods: 237 elite junior Australian football players completed FMS testing during the late pre-season phase and had their weekly playing status monitored during the regular season. The definition of an injury was ‘a trauma which caused a player to miss a competitive match’. Results: The median composite FMS score was 14 (mean = 13.5 ± 2.3). An apriori analysis revealed that the presence of ≥1 asymmetrical sub-test was associated with a moderate increase in the risk of injury (hazard ratio = 2.2 [1.0–4.8]; relative risk = 1.9; p = 0.047; sensitivity = 78.4%; specificity = 41.0%). Notably, post-hoc analysis identified that the presence of ≥2 asymmetrical sub-tests was associated with an even greater increase in risk of prospective injury (hazard ratio = 3.7 [1.6–8.6]; relative risk = 2.8; p = 0.003; sensitivity = 66.7%; specificity = 78.0%). Achieving a composite score of ≤14 did not substantially increase the risk of prospective injury (hazard ratio = 1.1 [0.5–2.1]; p = 0.834). Conclusions: Junior Australian football players demonstrating asymmetrical movement during pre-season FMS testing were more likely to sustain an injury during the regular season than players without asymmetry. Findings suggest that the commonly reported composite FMS threshold score of ≤14 was not associated with injury in elite junior AF players