Children’s sedentary behaviour: descriptive epidemiology and associations with objectively-measured sedentary time

Background: Little is known regarding the patterning and socio-demographic distribution of multiple sedentary behaviours in children. The aims of this study were to: 1) describe the leisure-time sedentary behaviour of 9-10 year old British children, and 2) establish associations with objectively-measured sedentary time. Methods: Cross-sectional analysis in the SPEEDY study (Sport, Physical activity and Eating behaviour: Environmental Determinants in Young people) (N=1513, 44.3% boys). Twelve leisure-time sedentary behaviours were assessed by questionnaire. Objectively-measured leisure-time sedentary time (Actigraph GT1M, <100 counts/minute) was assessed over 7 days. Differences by sex and socioeconomic status (SES) in self-reported sedentary behaviours were tested using Kruskal-Wallis tests. The association between objectively-measured sedentary time and the separate sedentary behaviours (continuous (minutes) and categorised into 'none' 'low' or 'high' participation) was assessed using multi-level linear regression. Results: Sex differences were observed for time spent in most sedentary behaviours (all p ≤ 0.02), except computer use. Girls spent more time in combined non-screen sedentary behaviour (median, interquartile range: girls: 770.0 minutes, 390.0-1230.0; boys: 725.0, 365.0 - 1182.5; p = 0.003), whereas boys spent more time in screen-based behaviours (girls: 540.0, 273.0 - 1050.0; boys: 885.0, 502.5 - 1665.0; p < 0.001). Time spent in five non-screen behaviours differed by SES, with higher values in those of higher SES (all p ≤ 0.001). Regression analyses with continuous exposures indicated that reading (β = 0.1, p < 0.001) and watching television (β = 0.04, p < 0.01) were positively associated with objectively-measured sedentary time, whilst playing board games (β = -0.12, p < 0.05) was negatively associated. Analysed in categorical form, sitting and talking (vs. none: 'low' β = 26.1,ns; 'high' 30.9, p < 0.05), playing video games (vs. none: 'low' β = 49.1, p < 0.01; 'high' 60.2, p < 0.01) and watching television (vs. lowest tertile: middle β = 22.2,ns; highest β = 31.9, p < 0.05) were positively associated with objectively-measured sedentary time whereas talking on the phone (vs. none: 'low' β = -38.5, p < 0.01; 'high' -60.2, p < 0.01) and using a computer/internet (vs. none: 'low' β = -30.7, p < 0.05; 'high' -4.2,ns) were negatively associated. Conclusions: Boys and girls and children of different socioeconomic backgrounds engage in different leisure-time sedentary behaviours. Whilst a number of behaviours may be predictive of total sedentary time, collectively they explain little overall variance. Future studies should consider a wide range of sedentary behaviours and incorporate objective measures to quantify sedentary time where possible

MAIT cells launch a rapid, robust and distinct hyperinflammatory response to bacterial superantigens and quickly acquire an anergic phenotype that impedes their cognate antimicrobial function: Defining a novel mechanism of superantigen-induced immunopathology and immunosuppression

Superantigens (SAgs) are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS). Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave. Equally important, early host responses to SAgs can be accompanied or followed by a state of immunosuppression, which in turn jeopardizes the host's ability to combat and clear infections. Unlike in mouse models, the mechanisms underlying SAg-associated immunosuppression in humans are ill-defined. In this work, we have identified a population of innate-like T cells, called mucosa-associated invariant T (MAIT) cells, as the most powerful source of pro-inflammatory cytokines after exposure to SAgs. We have utilized primary human peripheral blood and hepatic mononuclear cells, mouse MAIT hybridoma lines, HLA-DR4-transgenic mice, MAIThighHLA-DR4+ bone marrow chimeras, and humanized NOD-scid IL-2Rγnull mice to demonstrate for the first time that: i) mouse and human MAIT cells are hyperresponsive to SAgs, typified by staphylococcal enterotoxin B (SEB); ii) the human MAIT cell response to SEB is rapid and far greater in magnitude than that launched by unfractionated conventional T, invariant natural killer T (iNKT) or γδ T cells, and is characterized by production of interferon (IFN)-γ, tumor necrosis factor (TNF)-α and interleukin (IL)-2, but not IL-17A; iii) high-affinity MHC class II interaction with SAgs, but not MHC-related protein 1 (MR1) participation, is required for MAIT cell activation; iv) MAIT cell responses to SEB can occur in a T cell receptor (TCR) Vβ-specific manner but are largely contributed by IL-12 and IL-18; v) as MAIT cells are primed by SAgs, they also begin to develop a molecular signature consistent with exhaustion and failure to participate in antimicrobial defense. Accordingly, they upregulate lymphocyte-activation gene 3 (LAG-3), T cell immunoglobulin and mucin-3 (TIM-3), and/or programmed cell death-1 (PD-1), and acquire an anergic phenotype that interferes with their cognate function against Klebsiella pneumoniae and Escherichia coli; vi) MAIT cell hyperactivation and anergy co-utilize a signaling pathway that is governed by p38 and MEK1/2. Collectively, our findings demonstrate a pathogenic, rather than protective, role for MAIT cells during infection. Furthermore, we propose a novel mechanism of SAg-associated immunosuppression in humans. MAIT cells may therefore provide an attractive therapeutic target for the management of both early and late phases of severe SAg-mediated illnesses

Very low prevalence of ultrasound detected tenosynovial abnormalities in healthy subjects throughout the age range: OMERACT ultrasound minimal disease study

Objectives: This study aimed to determine the prevalence of ultrasound detected tendon abnormalities in healthy subjects (HS) across the age range. / Methods: Adult HS (age 18 to 80 years) were recruited in 23 international Outcome Measures in Rheumatology (OMERACT) ultrasound centres and clinically assessed to exclude inflammatory diseases or overt osteoarthritis before undergoing a bilateral ultrasound examination of digit flexor (DF) 1-5 and extensor carpi ulnaris (ECU) tendons to detect the presence of tenosynovial hypertrophy (TSH), power Doppler (TPD) and tenosynovial effusion (TEF), usually considered ultrasound signs of inflammatory diseases. A comparison cohort of Rheumatoid Arthritis (RA) patients was taken from the Birmingham BEACON early arthritis inception cohort. / Results: 939 HS and 144 RA patients were included. The majority of HS (85%) had grade 0 for TSH, TPD and TEF in all DF and ECU tendons examined. There was statistically significant difference in the proportion of TSH and TPD involvement between HS and RA subjects (HS vs RA p<0.001). In HS there was no difference in the presence of ultrasound abnormalities between age groups. / Conclusions: Ultrasound detected TSH and TPD abnormalities are rare in HS and can be regarded as markers of active inflammatory disease in newly presenting suspected RA

Staphylococcus aureus nasal carriage is associated with serum 25-hydroxyvitamin D levels, gender and smoking status. The Tromsø Staph and Skin Study

Vitamin D induces the expression of antimicrobial peptides with activity against Staphylococcus aureus. Thus, we studied the association between serum 25-hydroxyvitamin D (25(OH)D) and S. aureus nasal colonization and carriage. Nasal swabs, blood samples and clinical data from 2,115 women and 1,674 men, aged 30–87 years, were collected in the Tromsø Staph and Skin Study 2007–08, as part of the population-based sixth Tromsø Study. Multivariate logistic regression analyses were stratified by recognized risk factors for S. aureus carriage: sex, age and smoking. In non-smoking men, we observed a 6.6% and 6.7% decrease in the probability of S. aureus colonization and carriage, respectively, by each 5 nmol/l increase in serum 25(OH)D concentration (P < 0.001 and P = 0.001), and serum 25(OH)D > 59 nmol/l and ≥75 nmol/l as thresholds for ~30% and ~50% reduction in S. aureus colonization and carriage. In non-smoking men aged 44–60 years, the odds ratio for S. aureus colonization was 0.44 (95% confidence interval, 0.28−0.69) in the top tertile of serum 25(OH)D versus the bottom tertile. In women and smokers there were no such associations. Our study supports that serum vitamin D is a determinant of S. aureus colonization and carriage

Membrane Cholesterol Regulates Lysosome-Plasma Membrane Fusion Events and Modulates Trypanosoma cruzi Invasion of Host Cells

Trypanosoma cruzi, is the etiological agent of a neglected tropical malady known as Chagas' disease, which affects about 8 million people in Latin America. 30–40% of affected individuals develop a symptomatic chronic infection, with cardiomyopathy being the most prevalent condition. T. cruzi utilizes an interesting strategy for entering cells: T. cruzi enhances intracellular calcium levels, which in turn trigger the exocytosis of lysosomal contents. Lysosomes then donate their membrane for the formation of the parasitophorous vacuole. Membrane rafts, cholesterol-enriched microdomains in the host cell plasma membrane, have also been implicated in T. cruzi invasion process. Since both plasma membrane and lysosomes collaborate in parasite invasion, we decided to study the importance of these membrane domains for lysosomal recruitment and fusion during T. cruzi invasion into host cells. Our results show that drug dependent depletion of plasma membrane cholesterol changes raft organization and induces excessive lysosome exocytosis in the earlier stages of treatment, leading to a depletion of lysosomes near the cell cortex, which in turn compromises T. cruzi invasion. Based on these results, we propose that cholesterol depletion leads to unregulated exocytic events of pre-docked lysosomes, reducing lysosome availability at the cell cortex and consequently compromising T. cruzi infection

Predicting sulfotyrosine sites using the random forest algorithm with significantly improved prediction accuracy

addresses: School of Biosciences, University of Exeter, Exeter EX4 5DE, UK. [email protected]: PMCID: PMC2777180types: Journal Article; Research Support, Non-U.S. Gov't© 2009 Yang; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Tyrosine sulfation is one of the most important posttranslational modifications. Due to its relevance to various disease developments, tyrosine sulfation has become the target for drug design. In order to facilitate efficient drug design, accurate prediction of sulfotyrosine sites is desirable. A predictor published seven years ago has been very successful with claimed prediction accuracy of 98%. However, it has a particularly low sensitivity when predicting sulfotyrosine sites in some newly sequenced proteins

Effect of Ibandronate on Bending Strength and Toughness on Rodent Cortical bone; possible implications for fracture prevention

OBJECTIVES: There remains conflicting evidence regarding cortical bone strength following bisphosphonate therapy. As part of a study to assess the effects of bisphosphonate treatment on the healing of rat tibial fractures, the mechanical properties and radiological density of the uninjured contralateral tibia was assessed. METHODS: Skeletally mature aged rats were used. A total of 14 rats received 1µg/kg ibandronate (iban) daily and 17 rats received 1 ml 0.9% sodium chloride (control) daily. Stress at failure and toughness of the tibial diaphysis were calculated following four-point bending tests. RESULTS: Uninjured cortical bone in the iban group had a significantly greater mean (standard deviation (sd)), p < 0.001, stress at failure of 219.2 MPa (sd 45.99) compared with the control group (169.46 MPa (sd 43.32)) following only nine weeks of therapy. Despite this, the cortical bone toughness and work to failure was similar. There was no significant difference in radiological density or physical dimensions of the cortical bone. CONCLUSIONS: Iban therapy increases the stress at failure of uninjured cortical bone. This has relevance when normalising the strength of repair in a limb when comparing it with the unfractured limb. However, the 20% increase in stress at failure with iban therapy needs to be interpreted with caution as there was no corresponding increase in toughness or work to failure. Further research is required in this area, especially with the increasing clinical burden of low-energy diaphyseal femoral fractures following prolonged use of bisphosphonates. Cite this article: Bone Joint Res 2015;4:99–10