Discordant inflammatory changes in the apophyseal and sacroiliac joints: serial observations in enthesitis-related arthritis

OBJECTIVE: To determine the extent to which inflammation of the sacroiliac joints (SIJs) and apophyseal joints (AJs) changes concordantly after treatment in enthesitis-related arthritis (ERA). METHODS: A retrospective study was performed with institutional review board approval. 31 young patients with ERA who had been scanned between March 2009 and November 2014 were included. All patients had post-contrast imaging of the SIJs and lumbar spine and short tau inversion-recovery (STIR) images of the SIJs. The severity of sacroiliitis was scored using a modification of an established technique, and inflammation of the AJs was evaluated using a recently described grading system. The changes in SIJ and AJ scores after treatment were classified as either concordant or discordant, and the proportion of scan pairs in these groups was recorded. In addition, the correlation between change in SIJ STIR score (Δnfla) and change in AJ score (ΔAJ) was assessed using Spearman's correlation coefficient. RESULTS: Of a total of 43 scan pairs, the changes in inflammation were concordant in 16 scan pairs and discordant in 27 scan pairs. There was no significant correlation between Δnfla and ΔAJ (R = 0.14, p = 0.37). CONCLUSION: Inflammatory changes in the SIJs and AJs are often discordant. This may be a reason why patients experience ongoing back pain despite apparent improvement in one or the other site. ADVANCES IN KNOWLEDGE: Inflammation may behave differently at different anatomical sites. The SIJs and AJs should both be imaged in patients with ERA with back pain

Predictors of change differ for moderate and vigorous intensity physical activity and for weekdays and weekends: a longitudinal analysis.

BACKGROUND: Predictors of physical activity (PA) change are rarely investigated separately for different PA intensities and for weekdays/weekends. We investigated whether individual-level predictors of one-year change in objectively-measured physical activity differ for moderate PA (MPA) and vigorous PA (VPA) and for weekends and weekdays. METHODS: Accelerometer-assessed PA (mins) was obtained at baseline and +1 year (n = 875, 41.5% male, Mean ± SD baseline age: 9.8 ± 0.4 years-old). Potential predictors (n = 38) were assessed at baseline from psychological (e.g., self-efficacy), socio-cultural (e.g., parent support) and environmental domains (e.g., land use). Associations between predictors and change in MPA (2000-3999 counts/minute (cpm)) and VPA (≥4000 cpm) separately for weekdays and weekends were studied using multi-level linear regression. Analyses were adjusted for school clustering, sex and baseline PA. RESULTS: Weekend PA declined (MPA decline 4.6 ± 21.8 mins/day; VPA decline: 2.1 ± 20.1 mins/day; both p < 0.001) whereas weekday PA did not significantly change. Higher baseline PA and being a girl were associated with greater PA declines in all four outcomes; remaining predictors differed for MPA and VPA and/or weekdays and weekends. Family logistic support was associated with less of a decline in weekend MPA (CI 95%) 0.15 (0.05, 0.25) and VPA 0.19 (0.09, 0.29), and peer support with less of a decline in weekday MPA 0.18 (0.02, 0.34) and VPA 0.22 (0.06, 0.38). CONCLUSIONS: Results highlight the relevance of investigating predictors of PA change separately for different PA intensities and for weekdays/weekends. In addition to continued focus on school PA promotion, more effort to target interventions during weekends, such as in the family and community appears important. Encouraging peer support to increase weekday PA and targeting parent support for weekend PA may be health promotion priorities.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Synthesis of oligodeoxyribonucleotides containing a tricyclic thio analogue of O6-methylguanine and their recognition by MGMT and Atl1

Promutagenic O6-alkylguanine adducts in DNA are repaired in humans by O6-methylguanine-DNA-methyltransferase (MGMT) in an irreversible reaction. Here we describe the synthesis of a phosphoramidite that allows the preparation of oligodeoxyribonucleotides (ODNs) containing a novel tricyclic thio analogue of O6-methylguanine in which the third ring bridges the 6-thio group and C7 of a 7-deazapurine. These ODNs are very poor substrates for MGMT and poorly recognised by the alkyltransferase-like protein, Atl1. Examination of the active sites of both MGMT and Atl1 suggest large steric clashes hindering binding of the analogue. Such analogues, if mutagenic, are likely to be highly toxic

Bioaccessibility of difenoconazole in rice following industry standard processing and preparation procedures

For pesticide registration a post application assessment is made on the safety of any residue remaining in the edible portion of the treated crop. This assessment does not typically consider the bioaccessibility of pesticide residues. The effects of this on potential exposure to incurred difenoconazole residues passing through the human gastrointestinal tract was studied, including the impact of commodity processing. It has previously been demonstrated that solvent extraction methods have the potential to overestimate the bioaccessible fraction, so in vitro simulated gut systems may offer a better approach to determine residue bioaccessibility to refine the risk assessment process. The bioaccessibility of difenoconazole residues associated with processed rice samples were assessed using in vitro intestinal extraction and colonic fermentation methods. Mean bioaccessibility following intestinal digestion was 33.3% with a range of 13% to 70.6%. Quantification of the colonic bioaccessible fraction was not possible due to compound metabolism. Mechanical processing methods generally increased the residue bioaccessibility while chemical methods resulted in a decrease. Both mechanical and chemical processing methods reduced the total difenoconazole residue level by c. 50%. M. 1, G.R Gibson2, P. Whalley1, C.D Collins3

The stringent response inhibits 70S ribosome formation in Staphylococcus aureus by impeding GTPase-ribosome interactions

During nutrient limitation, bacteria produce the alarmones (p)ppGpp as effectors of a stress signaling network termed the stringent response. RsgA, RbgA, Era, and HflX are four ribosome-associated GTPases (RA-GTPases) that bind to (p)ppGpp in Staphylococcus aureus. These enzymes are cofactors in ribosome assembly, where they cycle between the ON (GTP-bound) and OFF (GDP-bound) ribosome-associated states. Entry into the OFF state occurs upon hydrolysis of GTP, with GTPase activity increasing substantially upon ribosome association. When bound to (p)ppGpp, GTPase activity is inhibited, reducing 70S ribosome assembly and growth. Here, we determine how (p)ppGpp impacts RA-GTPase-ribosome interactions. We show that RA-GTPases preferentially bind to 59-diphosphate-containing nucleotides GDP and ppGpp over GTP, which is likely exploited as a regulatory mechanism within the cell to shut down ribosome biogenesis during stress. Stopped-flow fluorescence and association assays reveal that when bound to (p)ppGpp, the association of RA-GTPases to ribosomal subunits is destabilized, both in vitro and within bacterial cells. Consistently, structural analysis of the ppGpp-bound RA-GTPase RsgA reveals an OFF-state conformation similar to the GDP-bound state, with the G2/switch I loop adopting a conformation incompatible with ribosome association. Altogether, we highlight (p)ppGpp-mediated inhibition of RA-GTPases as a major mechanism of stringent response-mediated ribosome assembly and growth control

3D-Printing Physical Activity in Youth: An Autotopographical Approach to Behaviour Change

The conceptualisation and visualisation of physical activity through 3D-printed objects offers a unique means by which to elicit positive behaviour change. This study aimed to explore whether 3D-printed models of physical activity obtain autotopographical meaning in youths and the influence of such models on their sense of personal and social identity. Following participation in a seven-week faded intervention, whereby habitual physical activity was measured and used to create individual 3D models, the views of 61 participants (36 boys; 10.9 ± 3.0 years) were explored via semi-structured focus groups. Within the over-arching theme of ‘3D-Printed Models’, key emergent sub-themes were structured around ‘Autotopography’, ‘Reflection’, ‘In-group norms’, and ‘Significant others’. Investing meaning in the material representations facilitated social activation and self-reflection on their own behaviour, both of which are key elements of identity formation. The influential role of significant others (familial and peers) within initial model interpretation and their potential long-term efficacy as a behaviour change approach was highlighted. 3D-printed models present a novel concept and intervention approach and may represent a useful component within behaviour change engagement strategies in children and adolescents

Small vessel disease pathological changes in neurodegenerative and vascular dementias concomitant with autonomic dysfunction

We performed a clinicopathological study to assess the burden of small vessel disease (SVD) type of pathological changes in elderly demented subjects, who had clinical evidence of autonomic dysfunction, either carotid sinus hypersensitivity or orthostatic hypotension or both or had exhibited unexpected repeated falls. Clinical and neuropathological diagnoses in 112 demented subjects comprised dementia with Lewy bodies (DLB), Parkinson's disease with dementia (PDD), Alzheimer's disease (AD), Mixed dementia (mostly AD‐DLB) and vascular dementia (VaD). Of these, 12 DLB subjects had no recorded unexpected falls in life and therefore no evidence of concomitant autonomic dysfunction. A further 17 subjects were assessed as aging controls without significant pathology or signs of autonomic dysfunction. We quantified brain vascular pathological changes and determined severities of neurodegenerative lesions including α‐synuclein pathology. We found moderate‐severe vascular changes and high‐vascular pathology scores (P < 0.01) in all neurodegenerative dementias and as expected in VaD compared to similar age controls. Arteriolosclerosis, perivascular spacing and microinfarcts were frequent in the basal ganglia and frontal white matter (WM) across all dementias, whereas small infarcts (<5 mm) were restricted to VaD. In a sub‐set of demented subjects, we found that vascular pathology scores were correlated with WM hyperintensity volumes determined by MRI in life (P < 0.02). Sclerotic index values were increased by ~50% in both the WM and neocortex in all dementias compared to similar age controls. We found no evidence for increased α‐synuclein deposition in subjects with autonomic dysfunction. Our findings suggest greater SVD pathological changes occur in the elderly diagnosed with neurodegenerative dementias including DLB and who develop autonomic dysfunction. SVD changes may not necessarily manifest in clinically overt symptoms but they likely confound motor or cognitive dysfunction. We propose dysautonomia promotes chronic cerebral hypoperfusion to impact upon aging‐related neurodegenerative disorders and characterize their end‐stage clinical syndromes

Environmental DNA persistence and fish detection in captive sponges.

Large and hyper-diverse marine ecosystems pose significant challenges to biodiversity monitoring. While environmental DNA (eDNA) promises to meet many of these challenges, recent studies suggested that sponges, as 'natural samplers' of eDNA, could further streamline the workflow for detecting marine vertebrates. However, beyond pilot studies demonstrating the ability of sponges to capture eDNA, little is known about the dynamics of eDNA particles in sponge tissue, and the effectiveness of the latter compared to water samples. Here, we present the results of a controlled aquarium experiment to examine the persistence and detectability of eDNA captured by three encrusting sponge species and compare the sponge's eDNA capturing ability with established water filtration techniques. Our results indicate that sponges and water samples have highly similar detectability for fish of different sizes and abundances, but different sponge species exhibit considerable variance in performance. Interestingly, one sponge appeared to mirror the eDNA degradation profile of water samples, while another sponge retained eDNA throughout the experiment. A third sponge yielded virtually no DNA sequences at all. Overall, our study suggests that some sponges will be suitable as natural samplers, while others will introduce significant problems for laboratory processing. We suggest that an initial optimization phase will be required in any future studies aiming to employ sponges for biodiversity assessment. With time, factoring in technical and natural accessibility, it is expected that specific sponge taxa may become the 'chosen' natural samplers in certain habitats and regions