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Comparative efficacy of pharmacological and non-pharmacological interventions for the acute treatment of adult outpatients with anorexia nervosa: study protocol for the systematic review and network metaanalysis of individual data
Get PDFThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background
Outpatient treatment studies of anorexia nervosa (AN) are notoriously hard to conduct given the ambivalence of the patient group and high drop-out rates. It is therefore not surprising that previous meta-analyses of pharmacological and psychological treatments for outpatient treatment of adult AN have proved to be inconclusive. Network meta-analysis (NMA) has the potential to overcome the limitations of pairwise meta-analysis, as this approach can compare multiple treatments using both direct comparisons of interventions within randomized controlled trials (RCTs) and indirect comparisons across trials based on a common comparator. To date there is no published example of this approach with eating disorders and the current study provides a protocol which will use NMA to advance knowledge about what outpatient therapy works best for which patients with AN by conducting both direct and indirect comparisons of different treatments and the moderating variables.
Methods
Searches of electronic data bases will be supplemented with manual searches for published, unpublished and ongoing RCTs in international registries, and clinical trials registries of regulatory agencies and pharmaceutical companies. Two reviewers will independently extract the data and where possible we will access individual data in order to examine moderators of treatment. Two primary outcomes will be selected: changes to body mass index and changes to global eating disorder psychopathology. The secondary outcome is the total number of patients who, at 12-month post-randomization, attained over the previous 28 day period: (i) BMI > 18.5, and (ii) global eating disorder psychopathology to within 1 SD of community norms. We will also provide a statistical evaluation of consistency, the agreement between direct and indirect evidence.
Results
Descriptive statistics across all eligible trials will be provided along with a network diagram, where the size of the nodes will reflect the amount of evidence accumulated for each treatment. We will use a contribution matrix that describes the percentage contribution of each direct meta-analysis to the entire body of evidence.
Discussion
Findings will make a major contribution to the literature by summarising individual data across rapidly accumulating outpatient trials of AN using state of the art NMA methodology
The Temporal Relationship between Arterial Stiffening and Blood Pressure Is Modified by Methotrexate Treatment in Patients with Rheumatoid Arthritis
Get PDFThis is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Background: The temporal relationship between arterial stiffness and blood pressure (BP) may vary depending on age and other clinical and demographic factors. Since both BP and arterial stiffness are also affected by inflammatory processes, we examined the temporal arterial stiffness-BP relationship in patients with rheumatoid arthritis (RA) treated with either methotrexate (MTX), an anti-rheumatic agent shown to reduce cardiovascular risk in meta-analyses, or other disease-modifying anti-rheumatic drugs (DMARDs).
Methods: Measurements of clinic and 24-h peripheral and central systolic and diastolic BP (SBP and DBP), and pulse wave velocity (PWV) were assessed in RA patients on stable treatment with either MTX ± other DMARDs (MTX group, n = 41, age 61 ± 14 years, 73% females) or other DMARDs (non-MTX group, n = 18, age 65 ± 13 years, 89% females). Measurements were performed at baseline and after 8 months. The temporal relationships were examined using cross-lagged path analysis with models that included age, sex, body mass index, prednisolone, and folic acid use and 28-joint disease activity score.
Results: There were significant differences in the temporal arterial stiffness-BP relationships between those in the MTX and DMARD groups. A higher PWV at baseline caused a significant increase in 6 out of 8 different measures of SBP at 8 months amongst those treated with DMARDs (standardized β, range = 0.54–0.66, p < 0.003 for each) and 3 out of 8 different measures of DBP (standardized β, range = 0.52–0.61, p < 0.003 for each) but was not associated with either SBP or DBP at 8 months amongst those treated with MTX. The difference in the effect of baseline PWV on 8-month BP between the 2 groups was also significant (p < 0.003) for 4 measures including clinic peripheral SBP (β = 7.0, 95% CI = 2.8–11.1 mmHg per 1 m/s higher baseline PWV; p < 0.001).
Conclusions: Higher arterial stiffness preceded increases in BP in subjects with RA treated with DMARDs, but these effects did not occur amongst those treated with MTX. The different effects were seen mostly in measures of SBP but were also present in some measures of DBP. Our findings suggest MTX may confer a protective effect against stiffness mediated increases in BP in patients with RA
Oral Mucosal Epithelial Cells Grown on Porous Silicon Membrane for Transfer to the Rat Eye
Get PDFOpen Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Dysfunction of limbal stem cells or their niche can result in painful, potentially sight-threatening ocular surface disease. We examined the utility of surface-modified porous-silicon (pSi) membranes as a scaffold for the transfer of oral mucosal cells to the eye. Male-origin rat oral mucosal epithelial cells were grown on pSi coated with collagen-IV and vitronectin, and characterised by immunocytochemistry. Scaffolds bearing cells were implanted into normal female rats, close to the limbus, for 8 weeks. Histology, immunohistochemistry and a multiplex nested PCR for sry were performed to detect transplanted cells. Oral mucosal epithelial cells expanded on pSi scaffolds expressed the corneal epithelial cell marker CK3/12. A large percentage of cells were p63+, indicative of proliferative potential, and a small proportion expressed ABCG2+, a putative stem cell marker. Cell-bearing scaffolds transferred to the eyes of live rats, were well tolerated, as assessed by endpoint histology. Immunohistochemistry for pan-cytokeratins demonstrated that transplanted epithelial cells were retained on the pSi membranes at 8 weeks post-implant, but were not detectable on the central cornea using PCR for sry. The pSi scaffolds supported and retained transplanted rat oral mucosal epithelial cells in vitro and in vivo and recapitulate some aspects of an artificial stem cell niche
Dilute, derivatise and shoot: Measurement of urinary free metanephrines and catecholamines as ethyl derivatives by LC-MSMS
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This author accepted manuscript is made available following 24 month embargo from date of publication (Sept 2017) in accordance with the publisher’s archiving policyBackground
The measurement of catecholamines and their metabolites in either urine or plasma is an important diagnostic test used to exclude the presence of neuroendocrine tumours. Because of weak chromatographic retention and potential ion-suppression, reverse-phase LC-MSMS is not ideal for analysis of these polar molecules. Here, we investigate derivatisation by ethylation as an alternative approach.
Methods
A simple and rapid method involving acetaldehyde and a reducing agent was used to convert urine free metanephrines and catecholamines, and their deuterated analogues as internal standards, to mono-ethyl or diethyl- derivatives. Using an Agilent 6460 triple-quadrupole mass spectrometer, precursor and product ion mass spectra were recorded to allow comparison of multiple reaction monitoring methods for both derivatised and non-derivatised analytes under reverse-phase LC-MSMS conditions with positive electrospray ionization.
Results
Conversion of biogenic amines to less polar ethyl derivatives increased their mass and enhanced the intensity of their molecular ions and fragments. Ethylation also improved the chromatographic properties of the amines, with greater retention and elution from reverse-phase HPLC columns with a methanol or acetonitrile gradient. The signal response of tandem mass spectrometric detection was increased up to 50-fold for ethyl metanephrines compared to non-derivatised compounds. This increase allowed for the omission of solid-phase extraction of urine as a clean-up step prior to analysis. The ‘dilute-derivatise-shoot’ method maintained analytical performance with respect to between-run imprecision (CV < 6%) and accuracy in an external quality assurance program. Gender-related ranges for free metanephrines in early-morning spot urines, collected from adult patients, were similar using either derivatised or non-derivatised samples.
Conclusions
The LC-MSMS detection of free urine biogenic amines can be greatly enhanced by ethyl derivatisation, which is easy and rapid to perform. Advantages include improved chromatography and lower limits of quantitation, that negate the requirement for solid-phase clean-up of urine prior to analysis. A disadvantage is the potential toxicity of the derivatising agents used if they are not handled appropriately
Lizards, ticks and contributions to Australian parasitology: C. Michael Bull (1947-2016)
Get PDFPublished by Elsevier Ltd on behalf of Australian Society for Parasitology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Professor C. Michael Bull was a great scientist and mentor, and an Associate Editor of this journal. While his research career spanned the fields of behavioural ecology, conservation biology and herpetology, in this article, we pay tribute to his major contribution to Australian parasitology. Mike authored more than eighty articles on host-parasite ecology, and revealed major insights into the biology and ecology of ticks from his long term study of the parapatric boundary of two tick species (Amblyomma limbatum and Bothriocroton hydrosauri) on the sleepy lizard (Tiliqua rugosa). In this article, we provide an overview of how this research journey developed to become one of the longest-running studies of lizards and their ticks, totalling 35 years of continuous surveys of ticks on lizards, and the insights and knowledge that he generated along that journey
Trisomy 12 assessment by conventional fluorescence in-situ hybridization (FISH), FISH in suspension (FISH-is) and laser scanning cytometry (LSC) in chronic lymphocytic leukemia.
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This author accepted manuscript is made available following 12 month embargo from date of publication (August 2017) in accordance with the publisher’s archiving policyChronic lymphocytic leukemia (CLL) has an extremely heterogeneous clinical course, and prognostication is based on common genetic abnormalities which are detected by standard cytogenetic methods. However, current methods are restricted by the low number of cells able to be analyzed, resulting in the potential to miss clinically relevant sub-clonal populations of cells. A novel high throughput methodology called fluorescence in situ hybridization in suspension (FISH-IS) incorporates a flow cytometry-based imaging approach with automated analysis of thousands of cells. Here we have demonstrated that the FISH-IS technique is applicable to aneuploidy detection in CLL samples for a range of chromosomes using appropriate centromere probes. This method is able to accurately differentiate between monosomy, disomy and trisomy with a sensitivity of 1% in CLL. An analysis comparing conventional FISH, FISH-IS and laser scanning cytometry (LSC) is presented
Is higher formula intake and limited dietary diversity in Australian children at 14 months of age associated with dietary quality at 24 months?
Get PDF© 2017 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
This author accepted manuscript is made available following 24 month embargo from date of publication (Sept 2017) in accordance with the publisher’s archiving policyA varied and diverse diet in childhood supports optimum long-term preferences and growth. Previous analysis from 14-month-old Australian children in the NOURISH and South Australian Infants Dietary Intake (SAIDI) studies found higher formula intake was associated with lower dietary diversity. This analysis investigated whether formula intake and dietary diversity at 14 months of age is associated with dietary quality at 24 months.
This is a secondary analysis of intake data from NOURISH and SAIDI cohorts. Scores for dietary diversity, fruit variety, vegetable variety and meat/alternative variety were combined using structural equation modelling to form the latent variable ‘Dietary quality’ (DQ) at age 24 months. A longitudinal model examined influence of formula (grams), cow's milk (grams) and dietary diversity at 14 months and covariates, on DQ.
At age 24 months (n = 337) 27% of children obtained a maximum dietary diversity score (5/5). Variety scores were relatively low – with mean variety scores (and possible range) being four for fruit (0–30); five for vegetables (0–36); and three for meat/alternatives (0–8). Dietary diversity at 14 months (β = 0.19, p = 0.001), maternal age (β = 0.24, p < 0.001) and education (β = 0.22, p < 0.001) predicted DQ at 24 months while Child Food Neophobia Score was negatively associated with DQ (β = −0.30, p < 0.001). Formula intake was negatively associated with diversity at 14 months, but not DQ at 24.
Diversity and variety were limited despite sociodemographic advantage of the sample. Diversity at 14 months, degree of neophobia and sociodemographic factors predicted DQ at 24 months. There is an ongoing need to emphasise the importance of repeated early exposure to healthy foods, such that children have the opportunity to learn to like a range of tastes and texture, thereby maximising dietary diversity and quality in infancy and early toddlerhood
A non-transcriptional role for the glucocorticoid receptor in mediating the cell stress response
Get PDFThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.The glucocorticoid receptor (GR) is essential for the stress response in mammals. We investigated potential non-transcriptional roles of GR in cellular stress response using fission yeast as a model.We surprisingly discovered marked heat stress resistance in yeast ectopically expressing human GR, which required expression of both the N-terminal transactivation domain, and the C-terminal ligand binding domain, but not the DNA-binding domain of the GR. This effect was not affected by GR ligand exposure, and occurred without significant GR nuclear accumulation. Mechanistically, the GR survival effect required Hsp104, and, indeed, GR expression increased Hsp104 expression. Proteomic analysis revealed GR binding to translasome components, including eIF3, a known partner for Sty1, a pattern of protein interaction which we confirmed using yeast two-hybrid studies.Taken together, we find evidence for a novel pathway conferring stress resistance in yeast that can be activated by the human GR, acting by protein-protein mechanisms in the cytoplasm. This suggests that in organisms where GR is natively expressed, GR likely contributes to stress responses through non-transcriptional mechanisms in addition to its well-established transcriptional responses
Effects of α-lipoic acid on growth performance, body composition, antioxidant status and lipid catabolism of juvenile Chinese mitten crab Eriocheir sinensis fed different lipid percentage
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This author accepted manuscript is made available following 24 month embargo from date of publication (Sept 2017) in accordance with the publisher’s archiving policyThis study evaluates the effects of dietary lipid percentage (7% and 13%) on growth performance, body composition, antioxidative status and hepatopancreas lipid catabolism of Chinese mitten crab Eriocheir sinensis. Each lipid diet was supplemented with three concentrations of α-lipoic acid at 0, 700 and 1400 mg/kg, and fed to E. sinensis juveniles for eight weeks. The weight gain and specific growth rate of crabs fed the diets supplemented with α-LA were significantly higher than those fed the control diet without α-LA, regardless of dietary lipid percentage. The α-LA significantly increased lipid accumulation in the whole body and hepatopancreas in a dose-dependent manner. Crabs fed 13% lipid showed a significantly higher hepatosomatic index than those fed 7% lipid. The mRNA expressions of triacylglycerol lipase and intracellular lipase increased with the increase of α-LA concentration in crabs fed 7% lipid. No significant difference was found in the CPT-1 mRNA expression among all treatments. The α-LA supplementation at 1400 mg/kg significantly improved oxidative stress due to lipid accumulation in the hepatopancreas of crabs fed 7% lipid as indicated by the high activity of superoxide dismutase and glutathione peroxidase and a low level of malondialdehyde. The diet with 13% lipid increased the lipid content in the hepatopancreas but suppressed glutathione peroxidase. Meanwhile, the total antioxidant capacity increased with the increase of α-LA concentration in crabs fed 13% lipid. This study indicates that α-LA supplementation can improve growth performance and accelerate lipid accumulation in the hepatopancreas by increasing lipid utilization efficiency. Furthermore, α-LA can relieve hepatopancreas oxidative damage induced by lipid accumulation and improve the health of E. sinensis
Shawarma, Muhummara and the Osh Guys
Get PDFFood is an important part of Arabic culture, and when you accept their food it is as though you accept them - even if you mess up the pronunciation