4,147 research outputs found
Macrophage activation syndrome triggered by coeliac disease: a unique case report
Background:
Macrophage activation syndrome is described as a “clinical syndrome of hyperinflammation resulting in an uncontrolled and ineffective immune response” in the context of an autoinflammatory or rheumatic disease. Current associations of macrophage activation syndrome with autoimmune disease most notably include a host of rheumatological conditions and inflammatory bowel disease. Epidemiological studies have shown that macrophage activation syndrome is precipitated by autoimmune disease more commonly than previously thought. Diagnosing the precipitating factor is essential for effective treatment and prognosis.
Case presentation:
We report a case of a six year old girl with coeliac disease diagnosed after two episodes of secondary haemophagocytic lymphohistiocytosis. Her condition only responded to treatment once the patient was placed on a gluten free diet. Further immunological testing confirmed anti-transglutaminase and anti-endomysial antibodies, however histological biopsy was deemed inappropriate due to the severity of her condition. She has remained stable with no further episodes of macrophage activation syndrome since commencing a gluten free diet.
Conclusion:
This case report is the first literature that links macrophage activation syndrome to coeliac disease and highlights the challenge of diagnosing coeliac disease with unusual features such as associated prolonged fever. Clinicians should have a low threshold for screening children with other autoimmune diseases for coeliac disease
Dual targeting NG2 and GD3A using Mab-Zap immunotoxin results in reduced glioma cell viability in vitro
Constraining sub-grid physics with high-redshift spatially-resolved metallicity distributions
Aims. We examine the role of energy feedback in shaping the distribution of metals within cosmological hydrodynamical simulations of L* disc galaxies. While negative abundance gradients today provide a boundary condition for galaxy evolution models, in support of inside-out disc growth, empirical evidence as to whether abundance gradients steepen or flatten with time remains highly contradictory.
Methods. We made use of a suite of L* discs, realised with and without "enhanced" feedback. All the simulations were produced using the smoothed particle hydrodynamics code Gasoline, and their in situ gas-phase metallicity gradients traced from redshift z similar to 2 to the present-day. Present-day age-metallicity relations and metallicity distribution functions were derived for each system.
Results. The "enhanced" feedback models, which have been shown to be in agreement with a broad range of empirical scaling relations, distribute energy and re-cycled ISM material over large scales and predict the existence of relatively "flat" and temporally invariant abundance gradients. Enhanced feedback schemes reduce significantly the scatter in the local stellar age-metallicity relation and, especially, the [O/Fe]-[Fe/H] relation. The local [O/Fe] distribution functions for our L* discs show clear bimodality, with peaks at [O/Fe] = -0.05 and +0.05 (for stars with [Fe/H] > -1), consistent with our earlier work on dwarf discs.
Conclusions. Our results with "enhanced" feedback are inconsistent with our earlier generation of simulations realised with "conservative" feedback. We conclude that spatially-resolved metallicity distributions, particularly at high-redshift, offer a unique and under-utilised constraint on the uncertain nature of stellar feedback processes
The role of feedback in shaping the structure of the interstellar medium
We present an analysis of the role of feedback in shaping the neutral hydrogen (H I) content of simulated disc galaxies. For our analysis, we have used two realizations of two separate Milky Way-like (similar to L star) discs - one employing a conservative feedback scheme (McMaster Unbiased Galaxy Survey), the other significantly more energetic [Making Galaxies In a Cosmological Context (MaGICC)]. To quantify the impact of these schemes, we generate zeroth moment (surface density) maps of the inferred H I distribution; construct power spectra associated with the underlying structure of the simulated cold interstellar medium, in addition to their radial surface density and velocity dispersion profiles. Our results are compared with a parallel, self-consistent, analysis of empirical data from The H I Nearby Galaxy Survey (THINGS). Single power-law fits (P proportional to k(gamma)) to the power spectra of the stronger feedback (MaGICC) runs (over spatial scales corresponding to similar to 0.5 to similar to 20 kpc) result in slopes consistent with those seen in the THINGS sample (gamma similar to -2.5). The weaker feedback (MUGS) runs exhibit shallower power-law slopes (gamma similar to -1.2). The power spectra of the MaGICC simulations are more consistent though with a two-component fit, with a flatter distribution of power on larger scales (i.e. gamma similar to -1.4 for scales in excess of similar to 2 kpc) and a steeper slope on scales below similar to 1 kpc (gamma similar to -5), qualitatively consistent with empirical claims, as well as our earlier work on dwarf discs. The radial H I surface density profiles of the MaGICC discs show a clear exponential behaviour, while those of the MUGS suite are essentially flat; both behaviours are encountered in nature, although the THINGS sample is more consistent with our stronger (MaGICC) feedback runs
The effects of exogenous growth factors on matrix metalloproteinase secretion by human brain tumour cells
Matrix metalloproteinases (MMPs) are a growing family of zinc-dependent endopeptidases that are capable of degrading various components of the extracellular matrix. These enzymes have been implicated in a variety of physiological and pathological conditions including embryogenesis and tumour invasion. The synthesis of many MMPs is thought to be regulated by growth factors, cytokines and hormones. In this study, we investigated the effects of five exogenous growth factors known to be expressed by gliomas [epidermal growth factor (EGF), basic growth factor (bFGF), transforming growth factor beta (TGF-β1,2) and vascular endothelial growth factor (VEGF)] on MMP-2 and MMP-9 expression in an ependymoma, two grade III astrocytomas, a grade III oligoastrocytoma and a benign meningioma. Zymogram analysis revealed that the effects of the growth factors depended upon the cell lines used in the study. Growth factors generally up-regulated MMP-2 and MMP-9 expression in the gliomas but were least effective in the meningioma; the effect being most prominent with TGF-β1 and TGF-β2 in all the cell lines. It is hypothesized that paracrine growth factor interplay may be crucial in the regulation of MMP expression by glioma invasion of the normal brain. © 2000 Cancer Research Campaig
A methodology review on the incremental prognostic value of computed tomography biomarkers in addition to Framingham risk score in predicting cardiovascular disease: the use of association, discrimination and reclassification
This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: Computed tomography (CT) biomarkers claim to improve cardiovascular risk stratification. This review
focuses on significant differences in incremental measures between adequate and inadequate reporting practise.
METHODS: Studies included were those that used Framingham Risk Score as a baseline and described the
incremental value of adding calcium score or CT coronary angiogram in predicting cardiovascular risk. Searches of
MEDLINE, EMBASE, Web of Science and Cochrane Central were performed with no language restriction.
RESULTS: Thirty five studies consisting of 206,663 patients (men = 118,114, 55.1%) were included. The baseline
Framingham Risk Score included the 1998, 2002 and 2008 iterations. Selective reporting, inconsistent reference
groupings and thresholds were found. Twelve studies (34.3%) had major and 23 (65.7%) had minor alterations and
the respective Δ AUC were significantly different (p = 0.015). When the baseline model performed well, the Δ AUC
was relatively lower with the addition of a CT biomarker (Spearman coefficient = − 0.46, p < 0.0001; n = 33; 76 pairs
of data). Other factors that influenced AUC performance included exploration of data analysis, calibration, validation,
multivariable and AUC documentation (all p < 0.05). Most studies (68.7%) that reported categorical NRI (n = 16; 46
pairs of data) subjectively drew strong conclusions along with other poor reporting practices. However, no
significant difference in values of NRI was found between adequate and inadequate reporting.
CONCLUSIONS: The widespread practice of poor reporting particularly association, discrimination, reclassification,
calibration and validation undermines the claimed incremental value of CT biomarkers over the Framingham Risk
Score alone. Inadequate reporting of discrimination inflates effect estimate, however, that is not necessarily the case
for reclassification.This research was funded by the National Insitute for Health Research (NIHR)
Collaboration for Leadership in Applied Health Research and Care South
West Peninsula (NIHR CLAHRC South West Peninsula)
The stellar metallicity distribution of disc galaxies and bulges in cosmological simulations
By means of high-resolution cosmological hydrodynamical simulations of Milky
Way-like disc galaxies, we conduct an analysis of the associated stellar
metallicity distribution functions (MDFs). After undertaking a kinematic
decomposition of each simulation into spheroid and disc sub-components, we
compare the predicted MDFs to those observed in the solar neighbourhood and the
Galactic bulge. The effects of the star formation density threshold are visible
in the star formation histories, which show a modulation in their behaviour
driven by the threshold. The derived MDFs show median metallicities lower by
0.2-0.3 dex than the MDF observed locally in the disc and in the Galactic
bulge. Possible reasons for this apparent discrepancy include the use of low
stellar yields and/or centrally-concentrated star formation. The dispersions
are larger than the one of the observed MDF; this could be due to simulated
discs being kinematically hotter relative to the Milky Way. The fraction of low
metallicity stars is largely overestimated, visible from the more negatively
skewed MDF with respect to the observational sample. For our fiducial Milky Way
analog, we study the metallicity distribution of the stars born "in situ"
relative to those formed via accretion (from disrupted satellites), and
demonstrate that this low-metallicity tail to the MDF is populated primarily by
accreted stars. Enhanced supernova and stellar radiation energy feedback to the
surrounding interstellar media of these pre-disrupted satellites is suggested
as an important regulator of the MDF skewness.Comment: 20 pages, 14 figures, MNRAS, accepte
Histopathological features of gastrointestinal mucosal biopsies in children with juvenile idiopathic arthritis
BACKGROUND: The association between inflammatory bowel disease and joint involvement is well established. There is a paucity of data describing histopathological features of the gut in relation to juvenile idiopathic arthritis (JIA). METHODS: We retrospectively identified 33 (21 male) children aged 3-16 y with JIA (11 with oligoarthritis, 5 with polyarthritis, 8 with systemic onset arthritis, 8 with enthesitis-related arthritis (ERA), and 1 with psoriatic arthritis) with significant gastrointestinal (GI) symptoms who underwent upper and/or lower endoscopy. The histopathological findings were reviewed in addition to presence of autoantibodies and concomitant treatment. RESULTS: The most common GI indications for endoscopy were persistent abdominal pain (14/33 (42%)) and diarrhea (10/33 (30%)). Of the 33 children, 28 (85%) had gut mucosal inflammation, mostly affecting the colon (80%). Active inflammation of the gut was found in 5 of 28 (17%) children, and 15 of 28 (53%) children showed mild nonspecific inflammation. Eight patients (27%) had predominantly an eosinophilic infiltrate. Twenty-six patients had previously received treatment for JIA. There was a negative association with the use of immunomodulators and the presence of eosinophil inflammation. CONCLUSION: The majority of children with JIA and GI symptoms have histological evidence of mild nonspecific inflammation, but some having active colitis and prominent eosinophil infiltrate
Built and natural environment planning principles for promoting health: An umbrella review
© 2018 The Author(s). Background: The built and natural environment and health are inextricably linked. However, there is considerable debate surrounding the strength and quality of the evidence base underpinning principles of good practice for built and natural environment design in promoting health. This umbrella review aimed to assess relationships between the built and natural environment and health, concentrating on five topic areas: neighbourhood design, housing, food environment, natural and sustainable environment, and transport. Methods: A structured search was conducted for quantitative systematic reviews and stakeholder reviews published between January 2005 and April 2016. Seven databases and the websites of 15 relevant and respected stakeholder organisations known to publish review-level documentation were searched. Searches were limited to English-language publications and duplicate references were removed. Evidence quality and strength was appraised using validated techniques. Findings were used to develop a diagram for each topic area, illustrating relationships between built and natural environment planning principles and health-related outcomes. Results: A total of 117 systematic reviews and review-level documents were eligible for inclusion. The quality of evidence was mixed; much of the evidence examined relied on findings from cross-sectional studies, making it difficult to draw clear causal links between built environment exposures and health-related impacts and outcomes. Fourteen actionable planning principles associated with positive health-related outcomes were identified across the five topic areas. For example, neighbourhoods that enhanced walkability, were complete and compact in design, and those which enhanced connectivity through safe and efficient infrastructure were associated with better health-related outcomes relating to physical activity, social engagement, mental health, perceptions of crime, and road traffic collisions. Evidence for the effectiveness of planning principles across different topic areas and on reducing health inequalities was sparse and inconclusive. Conclusions: Findings provide an up-to-date overview of relationships between the built and natural environment and health and present logical, evidence-based messages to aid communication between public health and planning professionals
Limited sensitivity and specificity of the ACR/EULAR-2019 classification criteria for SLE in JSLE?—observations from the UK JSLE Cohort Study
Objectives:
This study aimed to test the performance of the new ACR and EULAR criteria, that include ANA positivity as entry criterion, in JSLE. /
Methods:
Performance of the ACR/EULAR-2019 criteria were compared with Systemic Lupus International Collaborating Clinics (SLICC-2012), using data from children and young people (CYP) in the UK JSLE Cohort Study (n = 482), with the ACR-1997 criteria used as reference standard. An unselected cohort of CYP positive for ANA (n = 129) was used to calculate positive/negative predictive values of the criteria. /
Results:
At both first and last visits, the number of patients fulfilling the different classification criteria varied significantly (P < 0.001). The sensitivity of the SLICC-2012 criteria was higher when compared with that of the ACR/EULAR-2019 criteria at first and last visits (98% vs 94% for first visit, and 98% vs 96% for last visit; P < 0.001), when all available CYP were considered. The ACR/EULAR-2019 criteria were more specific when compared with the SLICC-2012 criteria (77% vs 67% for first visit, and 81% vs 71% for last visit; P < 0.001). Significant differences between the classification criteria were mainly caused by the variation in ANA positivity across ages. In the unselected cohort of ANA-positive CYP, the ACR/EULAR-2019 criteria produced the highest false-positive classification (6/129, 5%). /
Conclusion:
In CYP, the ACR/EULAR-2019 criteria are not superior to those of the SLICC-2012 or ACR-1997 criteria. If classification criteria are designed to include CYP and adult populations, paediatric rheumatologists should be included in the consensus and evaluation process, as seemingly minor changes can significantly affect outcomes
- …