Sport-Related Concussion and Mental Health Outcomes in Elite Athletes: A Systematic Review

BACKGROUND: Elite athletes can experience a diverse range of symptoms following post-concussive injury. The impact of sport-related concussion on specific mental health outcomes is unclear in this population. OBJECTIVE: The aim was to appraise the evidence base regarding the association between sport-related concussion and mental health outcomes in athletes competing at elite and professional levels. METHODS: A systematic search of PubMed, EMBASE, SPORTDiscus, PsycINFO, Cochrane, and Cinahl databases was conducted. RESULTS: A total of 27 studies met inclusion criteria for review. Most of the included studies (67%, n = 18) were published in 2014 or later. Study methodology and reporting varied markedly. The extant research has been conducted predominantly in North America (USA, n = 23 studies; Canada, n = 3), often in male only (44.4%, n = 12) and college (70.4%, n = 19) samples. Depression is the most commonly studied mental health outcome (70.4%, n = 19 studies). Cross-sectional retrospective studies and studies including a control comparison tend to support an association between concussion exposure and depression symptoms, although several studies report that these symptoms resolved in the medium term (i.e. 1 month) post-concussion. Evidence for anxiety is mixed. There are insufficient studies to draw conclusions for other mental health domains. CONCLUSION: Consistent with current recommendations to assess mood disturbance in post-concussive examinations, current evidence suggests a link between sports-related concussion and depression symptoms in elite athletes. Causation cannot be determined at this stage of enquiry because of the lack of well-designed, prospective studies. More research is required that considers a range of mental health outcomes in diverse samples of elite athletes/sports

Direct measurement of antiferromagnetic domain fluctuations

Measurements of magnetic noise emanating from ferromagnets due to domain motion were first carried out nearly 100 years ago and have underpinned much science and technology. Antiferromagnets, which carry no net external magnetic dipole moment, yet have a periodic arrangement of the electron spins extending over macroscopic distances, should also display magnetic noise, but this must be sampled at spatial wavelengths of order several interatomic spacings, rather than the macroscopic scales characteristic of ferromagnets. Here we present the first direct measurement of the fluctuations in the nanometre-scale spin- (charge-) density wave superstructure associated with antiferromagnetism in elemental Chromium. The technique used is X-ray Photon Correlation Spectroscopy, where coherent x-ray diffraction produces a speckle pattern that serves as a "fingerprint" of a particular magnetic domain configuration. The temporal evolution of the patterns corresponds to domain walls advancing and retreating over micron distances. While the domain wall motion is thermally activated at temperatures above 100K, it is not so at lower temperatures, and indeed has a rate which saturates at a finite value - consistent with quantum fluctuations - on cooling below 40K. Our work is important because it provides an important new measurement tool for antiferromagnetic domain engineering as well as revealing a fundamental new fact about spin dynamics in the simplest antiferromagnet.Comment: 19 pages, 4 figure

Grey and white matter correlates of recent and remote autobiographical memory retrieval:Insights from the dementias

The capacity to remember self-referential past events relies on the integrity of a distributed neural network. Controversy exists, however, regarding the involvement of specific brain structures for the retrieval of recently experienced versus more distant events. Here, we explored how characteristic patterns of atrophy in neurodegenerative disorders differentially disrupt remote versus recent autobiographical memory. Eleven behavioural-variant frontotemporal dementia, 10 semantic dementia, 15 Alzheimer's disease patients and 14 healthy older Controls completed the Autobiographical Interview. All patient groups displayed significant remote memory impairments relative to Controls. Similarly, recent period retrieval was significantly compromised in behavioural-variant frontotemporal dementia and Alzheimer's disease, yet semantic dementia patients scored in line with Controls. Voxel-based morphometry and diffusion tensor imaging analyses, for all participants combined, were conducted to investigate grey and white matter correlates of remote and recent autobiographical memory retrieval. Neural correlates common to both recent and remote time periods were identified, including the hippocampus, medial prefrontal, and frontopolar cortices, and the forceps minor and left hippocampal portion of the cingulum bundle. Regions exclusively implicated in each time period were also identified. The integrity of the anterior temporal cortices was related to the retrieval of remote memories, whereas the posterior cingulate cortex emerged as a structure significantly associated with recent autobiographical memory retrieval. This study represents the first investigation of the grey and white matter correlates of remote and recent autobiographical memory retrieval in neurodegenerative disorders. Our findings demonstrate the importance of core brain structures, including the medial prefrontal cortex and hippocampus, irrespective of time period, and point towards the contribution of discrete regions in mediating successful retrieval of distant versus recently experienced events

Primary cilia elongation in response to interleukin-1 mediates the inflammatory response

Primary cilia are singular, cytoskeletal organelles present in the majority of mammalian cell types where they function as coordinating centres for mechanotransduction, Wnt and hedgehog signalling. The length of the primary cilium is proposed to modulate cilia function, governed in part by the activity of intraflagellar transport (IFT). In articular cartilage, primary cilia length is increased and hedgehog signaling activated in osteoarthritis (OA). Here, we examine primary cilia length with exposure to the quintessential inflammatory cytokine interleukin-1 (IL-1), which is up-regulated in OA. We then test the hypothesis that the cilium is involved in mediating the downstream inflammatory response. Primary chondrocytes treated with IL-1 exhibited a 50 % increase in cilia length after 3 h exposure. IL-1-induced cilia elongation was also observed in human fibroblasts. In chondrocytes, this elongation occurred via a protein kinase A (PKA)-dependent mechanism. G-protein coupled adenylate cyclase also regulated the length of chondrocyte primary cilia but not downstream of IL-1. Chondrocytes treated with IL-1 exhibit a characteristic increase in the release of the inflammatory chemokines, nitric oxide and prostaglandin E2. However, in cells with a mutation in IFT88 whereby the cilia structure is lost, this response to IL-1 was significantly attenuated and, in the case of nitric oxide, completely abolished. Inhibition of IL-1-induced cilia elongation by PKA inhibition also attenuated the chemokine response. These results suggest that cilia assembly regulates the response to inflammatory cytokines. Therefore, the cilia proteome may provide a novel therapeutic target for the treatment of inflammatory pathologies, including OA

Induction of Sodium/Iodide Symporter (NIS) Expression and Radioiodine Uptake in Non-Thyroid Cancer Cells

Background: This study was designed to explore the therapeutic potential of suppressing MAP kinase and PI3K/Akt pathways and histone deacetylase (HDAC) to induce the expression of sodium/iodide symporter (NIS) and radioiodine uptake in non-thyroid cancer cells. Methods: We tested the effects of the MEK inhibitor RDEA119, the Akt inhibitor perifosine, and the HDAC inhibitor SAHA on NIS expression in thirteen human cancer cell lines derived from melanoma, hepatic carcinoma, gastric carcinoma, colon carcinoma, breast carcinoma, and brain cancers. We also examined radioiodine uptake and histone acetylation at the NIS promoter in selected cells. Results: Overall, the three inhibitors could induce NIS expression, to various extents, in melanoma and all the epithelial carcinoma-derived cells but not in brain cancer-derived cells. SAHA was most effective and its effect could be significantly enhanced by RDEA119 and perifosine. The expression of NIS, at both mRNA and protein levels, was most robust in the melanoma cell M14, hepatic carcinoma cell HepG2, and the gastric carcinoma cell MKN-7 cell. Radioiodine uptake was correspondingly induced, accompanied by robust increase in histone acetylation at the NIS promoter, in these cells when treated with the three inhibitors. Conclusions: This is the first demonstration that simultaneously suppressing the MAP kinase and PI3K/Akt pathways and HDAC could induce robust NIS expression and radioiodine uptake in certain non-thyroid human cancer cells, providing novel therapeutic implications for adjunct radioiodine treatment of these cancers

Intrinsic honesty and the prevalence of rule violations across societies

Deception is common in nature and humans are no exception. Modern societies have created institutions to control cheating, but many situations remain where only intrinsic honesty keeps people from cheating and violating rules. Psychological, sociological and economic theories suggest causal pathways to explain how the prevalence of rule violations in people’s social environment, such as corruption, tax evasion or political fraud, can compromise individual intrinsic honesty. Here we present cross-societal experiments from 23 countries around the world that demonstrate a robust link between the prevalence of rule violations and intrinsic honesty. We developed an index of the ‘prevalence of rule violations’ (PRV) based on country-level data from the year 2003 of corruption, tax evasion and fraudulent politics. We measured intrinsic honesty in an anonymous die-rolling experiment. We conducted the experiments with 2,568 young participants (students) who, due to their young age in 2003, could not have influenced PRV in 2003. We find individual intrinsic honesty is stronger in the subject pools of low PRV countries than those of high PRV countries. The details of lying patterns support psychological theories of honesty. The results are consistent with theories of the cultural co-evolution of institutions and values, and show that weak institutions and cultural legacies that generate rule violations not only have direct adverse economic consequences, but might also impair individual intrinsic honesty that is crucial for the smooth functioning of society

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Structural equation and log-linear modeling: a comparison of methods in the analysis of a study on caregivers' health

BACKGROUND: In this paper we compare the results in an analysis of determinants of caregivers' health derived from two approaches, a structural equation model and a log-linear model, using the same data set. METHODS: The data were collected from a cross-sectional population-based sample of 468 families in Ontario, Canada who had a child with cerebral palsy (CP). The self-completed questionnaires and the home-based interviews used in this study included scales reflecting socio-economic status, child and caregiver characteristics, and the physical and psychological well-being of the caregivers. Both analytic models were used to evaluate the relationships between child behaviour, caregiving demands, coping factors, and the well-being of primary caregivers of children with CP. RESULTS: The results were compared, together with an assessment of the positive and negative aspects of each approach, including their practical and conceptual implications. CONCLUSION: No important differences were found in the substantive conclusions of the two analyses. The broad confirmation of the Structural Equation Modeling (SEM) results by the Log-linear Modeling (LLM) provided some reassurance that the SEM had been adequately specified, and that it broadly fitted the data

Psychometric properties of the Quality of Life Inventory-Disability (QI-Disability) measure

PURPOSE: Children with intellectual disability encounter daily challenges beyond those captured in current quality of life measures. This study evaluated a new parent-report measure for children with intellectual disability, the Quality of Life Inventory-Disability (QI-Disability). METHODS: QI-Disability was administered to 253 primary caregivers of children (aged 5-18 years) with intellectual disability across four diagnostic groups: Rett syndrome, Down syndrome, cerebral palsy or autism spectrum disorder. Exploratory and confirmatory factor analyses were conducted and goodness of fit of the factor structure assessed. Associations between QI-Disability scores, and diagnostic and age groups were examined with linear regression. RESULTS: Six domains were identified: physical health, positive emotions, negative emotions, social interaction, leisure and the outdoors, and independence. Goodness-of-fit statistics were satisfactory and similar for the whole sample and when the sample was split by ability to walk or talk. On 100 point scales and compared to Rett syndrome, children with Down syndrome had higher leisure and the outdoors (coefficient 10.6, 95% CI 3.4,17.8) and independence (coefficient 29.7, 95% CI 22.9, 36.5) scores, whereas children with autism spectrum disorder had lower social interaction scores (coefficient -?12.8, 95% CI -?19.3, -?6.4). Scores for positive emotions (coefficient -?6.1, 95% CI -?10.7, -?1.6) and leisure and the outdoors (coefficient 5.4, 95% CI -?10.6, -?0.1) were lower for adolescents compared with children. CONCLUSIONS: Initial evaluation suggests that QI-Disability is a reliable and valid measure of quality of life across the spectrum of intellectual disability. It has the potential to allow clearer identification of support needs and measure responsiveness to interventions

Interpreting linear support vector machine models with heat map molecule coloring

<p>Abstract</p> <p>Background</p> <p>Model-based virtual screening plays an important role in the early drug discovery stage. The outcomes of high-throughput screenings are a valuable source for machine learning algorithms to infer such models. Besides a strong performance, the interpretability of a machine learning model is a desired property to guide the optimization of a compound in later drug discovery stages. Linear support vector machines showed to have a convincing performance on large-scale data sets. The goal of this study is to present a heat map molecule coloring technique to interpret linear support vector machine models. Based on the weights of a linear model, the visualization approach colors each atom and bond of a compound according to its importance for activity.</p> <p>Results</p> <p>We evaluated our approach on a toxicity data set, a chromosome aberration data set, and the maximum unbiased validation data sets. The experiments show that our method sensibly visualizes structure-property and structure-activity relationships of a linear support vector machine model. The coloring of ligands in the binding pocket of several crystal structures of a maximum unbiased validation data set target indicates that our approach assists to determine the correct ligand orientation in the binding pocket. Additionally, the heat map coloring enables the identification of substructures important for the binding of an inhibitor.</p> <p>Conclusions</p> <p>In combination with heat map coloring, linear support vector machine models can help to guide the modification of a compound in later stages of drug discovery. Particularly substructures identified as important by our method might be a starting point for optimization of a lead compound. The heat map coloring should be considered as complementary to structure based modeling approaches. As such, it helps to get a better understanding of the binding mode of an inhibitor.</p