Validity and sensitivity to change of laser Doppler imaging as a novel objective outcome measure for cutaneous lupus erythematosus.

OBJECTIVES:The objectives of this study were to assess the reliability of a novel objective outcome measure, laser Doppler imaging (LDI), its validity against skin biopsy histology and other clinical instruments, including localized cutaneous lupus disease area and severity index (L-CLASI) and visual analogue scale (VAS) score of photographs, and its responsiveness to clinical change with therapy. METHODS:A prospective observational cohort study was conducted in 30 patients with active cutaneous lupus erythematosus (CLE). At baseline and 3 months, disease activity was assessed using L-CLASI and a high resolution LDI system by two assessors. Skin biopsy was scored as 0 = non-active, 1 = mild activity and 2 = active. Photographs were assessed by two clinicians using 100 mm VAS. Inter-rater reliability was analyzed using Bland-Altman limits of agreement. Correlation between histology and LDI, L-CLASI and VAS and sensitivity to change of LDI with physician subjective assessment of change (PSAC) at 3 months were analyzed using Kendall's tau-a. RESULTS:Of 30 patients with CLE, 28 (93%) were female, mean (SD) age 48.4 (11.5) y, 25 (83%) were Caucasians, 25 (83%) had concurrent systemic lupus erythematosus and 16 (53%) were smokers. CLE subtypes were acute = 9, subacute = 8 and chronic = 13. Inter-rater agreement for LDI was fair but for VAS score of photographs was poor. In 20 patients with biopsy, correlation with histology was better for LDI (tau-a = 0.53) than L-CLASI (tau-a = 0.26) (difference = 0.27; 90% CI 0.05-0.49) or VAS score of photographs (tau-a = 0.17) (difference = 0.36; 90% CI 0.04-0.68). There was a moderate correlation between PSAC score and change in LDI (tau-a = 0.56; 90% CI 0.38-0.74; p < 0.001, n = 15). CONCLUSION:LDI provides a reliable, valid and responsive quantitative measure of inflammation in CLE. It has a better correlation with histology compared to clinical instruments. LDI provides an objective outcome measure for clinical trials

Characterisation of different polymorphs of tris(8-hydroxyquinolinato)aluminium(III) using solid-state NMR and DFT calculations

<p>Abstract</p> <p>Background</p> <p>Organic light emitting devices (OLED) are becoming important and characterisation of them, in terms of structure, charge distribution, and intermolecular interactions, is important. Tris(8-hydroxyquinolinato)-aluminium(III), known as Alq₃, an organomettalic complex has become a reference material of great importance in OLED. It is important to elucidate the structural details of Alq₃in its various isomeric and solvated forms. Solid-state nuclear magnetic resonance (NMR) is a useful tool for this which can also complement the information obtained with X-ray diffraction studies.</p> <p>Results</p> <p>We report here ²⁷Al one-dimensional (1D) and two-dimensional (2D) multiple-quantum magic-angle spinning (MQMAS) NMR studies of the meridional (<it>α</it>-phase) and the facial (<it>δ</it>-phase) isomeric forms of Alq₃. Quadrupolar parameters are estimated from the 1D spectra under MAS and anisotropic slices of the 2D spectra and also calculated using DFT (density functional theory) quantum-chemical calculations. We have also studied solvated phase of Alq₃containing ethanol in its lattice. We show that both the XRD patterns and the quadrupolar parameters of the solvated phase are different from both the <it>α</it>-phase and the <it>δ</it>-phase, although the fluorescence emission shows no substantial difference between the <it>α</it>-phase and the solvated phase. Moreover, we have shown that after the removal of ethanol from the matrix the solvated Alq₃has similar XRD patterns and quadrupolar parameters to that of the <it>α</it>-phase.</p> <p>Conclusion</p> <p>The 2D MQMAS experiments have shown that all the different modifications of Alq₃have ²⁷Al in single unique crystallographic site. The quadrupolar parameters predicted using the DFT calculation under the isodensity polarisable continuum model resemble closely the experimentally obtained values. The solvated phase of Alq₃containing ethanol has structural difference from the <it>α</it>-phase of Alq₃(containing meridional isomer) from the solid-state NMR studies. Solid-state NMR can hence be used as an effective complementary tool to XRD for characterisation and structural elucidation.</p

Protease-sensitive synthetic prions

Prions arise when the cellular prion protein (PrP(C)) undergoes a self-propagating conformational change; the resulting infectious conformer is designated PrP(Sc). Frequently, PrP(Sc) is protease-resistant but protease-sensitive (s) prions have been isolated in humans and other animals. We report here that protease-sensitive, synthetic prions were generated in vitro during polymerization of recombinant (rec) PrP into amyloid fibers. In 22 independent experiments, recPrP amyloid preparations, but not recPrP monomers or oligomers, transmitted disease to transgenic mice (n = 164), denoted Tg9949 mice, that overexpress N-terminally truncated PrP. Tg9949 control mice (n = 174) did not spontaneously generate prions although they were prone to late-onset spontaneous neurological dysfunction. When synthetic prion isolates from infected Tg9949 mice were serially transmitted in the same line of mice, they exhibited sPrP(Sc) and caused neurodegeneration. Interestingly, these protease-sensitive prions did not shorten the life span of Tg9949 mice despite causing extensive neurodegeneration. We inoculated three synthetic prion isolates into Tg4053 mice that overexpress full-length PrP; Tg4053 mice are not prone to developing spontaneous neurological dysfunction. The synthetic prion isolates caused disease in 600-750 days in Tg4053 mice, which exhibited sPrP(Sc). These novel synthetic prions demonstrate that conformational changes in wild-type PrP can produce mouse prions composed exclusively of sPrP(Sc)

Effects of a home-based intervention on diet and physical activity behaviours for rural adults with or at risk of metabolic syndrome: a randomised controlled trial

BACKGROUND: This study aimed to determine whether a home-based 6-month lifestyle intervention program complemented by motivational interviewing could improve diet and physical activity behaviours in 50-69 year olds with or at risk of metabolic syndrome, residing in a disadvantaged rural Western Australian community. METHODS: Participants from the City of Albany and surrounding towns (n?=?401) were recruited into a 6 month randomised controlled trial. They were screened for metabolic syndrome and randomly allocated to intervention (n?=?201) or control group (n?=?200). Baseline and post-test data collection for both groups included a self-report questionnaire which incorporated the Fat and Fibre Barometer and the International Physical Activity Questionnaire Short Form. The intervention group received the program materials at baseline and the control group was waitlisted. Generalised estimating equation models assessed repeated outcome measures over time. RESULTS: A total of 151 (75.1 %) intervention and 159 (79.5 %) control group participants completed post-test and were included in the analysis. After controlling for confounders, the intervention group achieved a marginally significant increase in their metabolic equivalent (MET) minutes of moderate intensity physical activity per week (p?=?0.049), and significantly improved fibre intake (p?&lt;?0.001), fat intake (p?=?0.003), and vegetable serves per day (p?=?0.002) from baseline to post-test relative to the control group. CONCLUSION: A home-based, low-cost intervention with motivational support can effectively improve the physical activity and dietary behaviours of adults aged 50-69 years with or at risk of metabolic syndrome residing in a disadvantaged rural area. TRIAL REGISTRATION: Anzctr.org.au Identifier: ACTRN12614000512628

Endocrinologic, neurologic, and visual morbidity after treatment for craniopharyngioma

Craniopharyngiomas are locally aggressive tumors which typically are focused in the sellar and suprasellar region near a number of critical neural and vascular structures mediating endocrinologic, behavioral, and visual functions. The present study aims to summarize and compare the published literature regarding morbidity resulting from treatment of craniopharyngioma. We performed a comprehensive search of the published English language literature to identify studies publishing outcome data of patients undergoing surgery for craniopharyngioma. Comparisons of the rates of endocrine, vascular, neurological, and visual complications were performed using Pearson’s chi-squared test, and covariates of interest were fitted into a multivariate logistic regression model. In our data set, 540 patients underwent surgical resection of their tumor. 138 patients received biopsy alone followed by some form of radiotherapy. Mean overall follow-up for all patients in these studies was 54 ± 1.8 months. The overall rate of new endocrinopathy for all patients undergoing surgical resection of their mass was 37% (95% CI = 33–41). Patients receiving GTR had over 2.5 times the rate of developing at least one endocrinopathy compared to patients receiving STR alone or STR + XRT (52 vs. 19 vs. 20%, χ2P < 0.00001). On multivariate analysis, GTR conferred a significant increase in the risk of endocrinopathy compared to STR + XRT (OR = 3.45, 95% CI = 2.05–5.81, P < 0.00001), after controlling for study size and the presence of significant hypothalamic involvement. There was a statistical trend towards worse visual outcomes in patients receiving XRT after STR compared to GTR or STR alone (GTR = 3.5% vs. STR 2.1% vs. STR + XRT 6.4%, P = 0.11). Given the difficulty in obtaining class 1 data regarding the treatment of this tumor, this study can serve as an estimate of expected outcomes for these patients, and guide decision making until these data are available

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability