2,395 research outputs found
Bodily Expression of Social Initiation Behaviors in ASC and non-ASC children: Mixed Reality vs. LEGO Game Play
This study is part of a larger project that showed the potential of our
mixed reality (MR) system in fostering social initiation behaviors
in children with Autism Spectrum Condition (ASC). We compared
it to a typical social intervention strategy based on construction
tools, where both mediated a face-to-face dyadic play session between
an ASC child and a non-ASC child. In this study, our first
goal is to show that an MR platform can be utilized to alter the
nonverbal body behavior between ASC and non-ASC during social
interaction as much as a traditional therapy setting (LEGO). A second
goal is to show how these body cues differ between ASC and
non-ASC children during social initiation in these two platforms.
We present our first analysis of the body cues generated under two
conditions in a repeated-measures design. Body cue measurements
were obtained through skeleton information and characterized in
the form of spatio-temporal features from both subjects individually
(e.g. distances between joints and velocities of joints), and
interpersonally (e.g. proximity and visual focus of attention). We
used machine learning techniques to analyze the visual data of eighteen
trials of ASC and non-ASC dyads. Our experiments showed
that: (i) there were differences between ASC and non-ASC bodily
expressions, both at individual and interpersonal level, in LEGO
and in the MR system during social initiation; (ii) the number of features
indicating differences between ASC and non-ASC in terms of
nonverbal behavior during initiation were higher in the MR system
as compared to LEGO; and (iii) computational models evaluated
with combination of these different features enabled the recognition
of social initiation type (ASC or non-ASC) from body features in
LEGO and in MR settings. We did not observe significant differences
between the evaluated models in terms of performance for LEGO
and MR environments. This might be interpreted as the MR system
encouraging similar nonverbal behaviors in children, perhaps more
similar than the LEGO environment, as the performance scores in
the MR setting are lower as compared to the LEGO setting. These
results demonstrate the potential benefits of full body interaction
and MR settings for children with ASC.EPSR
Borderline gestational diabetes mellitus and pregnancy outcomes
Background: The impact of borderline gestational diabetes mellitus (BGDM), defined as a positive oral glucose challenge test (OGCT) and normal oral glucose tolerance test (OGTT), on maternal and infant health is unclear. We assessed maternal and infant health outcomes in women with BGDM and compared these to women who had a normal OGCT screen for gestational diabetes. Methods: We compared demographic, obstetric and neonatal outcomes between women participating in the Australian Collaborative Trial of Supplements with antioxidants Vitamin C and Vitamin E to pregnant women for the prevention of pre-eclampsia (ACTS) who had BGDM and who screened negative on OGCT. Results: Women who had BGDM were older (mean difference 1.3 years, [95% confidence interval (CI) 0.3, 2.2], p = 0.01) and more likely to be obese (27.1% vs 14.1%, relative risk (RR) 1.92, [95% CI 1.41, 2.62], p < 0.0001) than women who screened negative on OGCT. The risk of adverse maternal outcome overall was higher (12.9% vs 8.1%, RR 1.59, [95% CI 1.00, 2.52], p = 0.05) in women with BGDM compared with women with a normal OGCT. Women with BGDM were more likely to develop pregnancy induced hypertension (17.9% vs 11.8%, RR 1.51, [95% CI 1.03, 2.20], p = 0.03), have a caesarean for fetal distress (17.1% vs 10.5%, RR 1.63, [95% CI 1.10, 2.41], p = 0.01), and require a longer postnatal hospital stay (mean difference 0.4 day, [95% CI 0.1, 0.7], p = 0.01) than those with a normal glucose tolerance. Infants born to BGDM mothers were more likely to be born preterm (10.7% vs 6.4%, RR 1.68, [95% CI 1.00, 2.80], p = 0.05), have macrosomia (birthweight ≥4.5 kg) (4.3% vs 1.7%, RR 2.53, [95% CI 1.06, 6.03], p = 0.04), be admitted to the neonatal intensive care unit (NICU) (6.5% vs 3.0%, RR 2.18, [95% CI 1.09, 4.36], p = 0.03) or the neonatal nursery (40.3% vs 28.4%, RR 1.42, [95% CI 1.14, 1.76], p = 0.002), and have a longer hospital stay (p = 0.001). More infants in the BGDM group had Sarnat stage 2 or 3 neonatal encephalopathy (12.9% vs 7.8%, RR 1.65, [95% CI 1.04, 2.63], p = 0.03). Conclusion: Women with BGDM and their infants had an increased risk of adverse health outcomes compared with women with a negative OGCT. Intervention strategies to reduce the risks for these women and their infants need evaluation. Trial registration: Current Controlled Trials ISRCTN00416244Hong Ju, Alice R. Rumbold, Kristyn J. Willson and Caroline A. Crowthe
Cost-effectiveness of cryotherapy versus salicylic acid for the treatment of plantar warts: economic evaluation alongside a randomised controlled trial (EVerT trial)
Background
Plantar warts (verrucae) are extremely common. Although many will spontaneously disappear without treatment, treatment may be sought for a variety of reasons such as discomfort. There are a number of different treatments for cutaneous warts, with salicylic acid and cryotherapy using liquid nitrogen being two of the most common forms of treatment. To date, no full economic evaluation of either salicylic acid or cryotherapy has been conducted based on the use of primary data in a pragmatic setting. This paper describes the cost-effectiveness analysis which was conducted alongside a pragmatic multicentre, randomised trial evaluating the clinical effectiveness of cryotherapy versus 50% salicylic acid of the treatment of plantar warts.
Methods
A cost-effectiveness analysis was undertaken alongside a pragmatic multicentre, randomised controlled trial assessing the clinical effectiveness of 50% salicylic acid and cryotherapy using liquid nitrogen at 12 weeks after randomisation of patients. Cost-effectiveness outcomes were expressed as the additional cost required to completely cure the plantar warts of one additional patient. A NHS perspective was taken for the analysis.
Results
Cryotherapy costs on average £101.17 (bias corrected and accelerated (BCA) 95% CI: 85.09-117.26) more per participant over the 12 week time-frame, while there is no additional benefit, in terms of proportion of patients healed compared with salicylic acid.
Conclusions
Cryotherapy is more costly and no more effective than salicylic acid
Investigating the role of c-Jun N-terminal kinases in the proliferation of Werner syndrome fibroblasts using diaminopyridine inhibitors
Fibroblasts derived from the progeroid Werner syndrome show reduced replicative lifespan and a "stressed" morphology, both alleviated using the MAP kinase inhibitor SB203580. However, interpretation of these data is problematical because although SB203580 has the stress-activated kinases p38 and JNK1/2 as its preferred targets, it does show relatively low overall kinase selectivity. Several lines of data support a role for both p38 and JNK1/2 activation in the control of cellular proliferation and also the pathology of diseases of ageing, including type II diabetes, diseases to which Werner Syndrome individuals are prone, thus making the use of JNK inhibitors attractive as possible therapeutics. We have thus tested the effects of the widely used JNK inhibitor SP600125 on the proliferation and morphology of WS cells. In addition we synthesised and tested two recently described aminopyridine based inhibitors. SP600125 treatment resulted in the cessation of proliferation of WS cells and resulted in a senescent-like cellular phenotype that does not appear to be related to the inhibition of JNK1/2. In contrast, use of the more selective aminopyridine CMPD 6o at concentrations that fully inhibit JNK1/2 had a positive effect on cellular proliferation of immortalised WS cells, but no effect on the replicative lifespan of primary WS fibroblasts. In addition, CMPD 6o corrected the stressed WS cellular morphology. The aminopyridine CMPD 6r, however, had little effect on WS cells. CMDP 6o was also found to be a weak inhibitor of MK2, which may partially explain its effects on WS cells, since MK2 is known to be involved in regulating cellular morphology via HSP27 phosphorylation, and is thought to play a role in cell cycle arrest. These data suggest that total JNK1/2 activity does not play a substantial role in the proliferation control in WS cells
Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.
The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD
Analysis of nucleic acid chaperoning by the prion protein and its inhibition by oligonucleotides
Prion diseases are unique neurodegenerative illnesses associated with the conversion of the cellular prion protein (PrPC) into the aggregated misfolded scrapie isoform, named PrPSc. Recent studies on the physiological role of PrPC revealed that this protein has probably multiple functions, notably in cell–cell adhesion and signal transduction, and in assisting nucleic acid folding. In fact, in vitro findings indicated that the human PrP (huPrP) possesses nucleic acid binding and annealing activities, similarly to nucleic acid chaperone proteins that play essential roles in cellular DNA and RNA metabolism. Here, we show that a peptide, representing the N-terminal domain of huPrP, facilitates nucleic acid annealing by two parallel pathways nucleated through the stem termini. We also show that PrP of human or ovine origin facilitates DNA strand exchange, ribozyme-directed cleavage of an RNA template and RNA trans-splicing in a manner similar to the nucleocapsid protein of HIV-1. In an attempt to characterize inhibitors of PrP-chaperoning in vitro we discovered that the thioaptamer 5′-GACACAAGCCGA-3′ was extensively inhibiting the PrP chaperoning activities. At the same time a recently characterized methylated oligoribonucleotide inhibiting the chaperoning activity of the HIV-1 nucleocapsid protein was poorly impairing the PrP chaperoning activities
Distal Xq duplication and functional Xq disomy
Distal Xq duplications refer to chromosomal disorders resulting from involvement of the long arm of the X chromosome (Xq). Clinical manifestations widely vary depending on the gender of the patient and on the gene content of the duplicated segment. Prevalence of Xq duplications remains unknown. About 40 cases of Xq28 functional disomy due to cytogenetically visible rearrangements, and about 50 cases of cryptic duplications encompassing the MECP2 gene have been reported. The most frequently reported distal duplications involve the Xq28 segment and yield a recognisable phenotype including distinctive facial features (premature closure of the fontanels or ridged metopic suture, broad face with full cheeks, epicanthal folds, large ears, small and open mouth, ear anomalies, pointed nose, abnormal palate and facial hypotonia), major axial hypotonia, severe developmental delay, severe feeding difficulties, abnormal genitalia and proneness to infections. Xq duplications may be caused either by an intrachromosomal duplication or an unbalanced X/Y or X/autosome translocation. In XY males, structural X disomy always results in functional disomy. In females, failure of X chromosome dosage compensation could result from a variety of mechanisms, including an unfavourable pattern of inactivation, a breakpoint separating an X segment from the X-inactivation centre in cis, or a small ring chromosome. The MECP2 gene in Xq28 is the most important dosage-sensitive gene responsible for the abnormal phenotype in duplications of distal Xq. Diagnosis is based on clinical features and is confirmed by CGH array techniques. Differential diagnoses include Prader-Willi syndrome and Alpha thalassaemia-mental retardation, X linked (ATR-X). The recurrence risk is significant if a structural rearrangement is present in one of the parent, the most frequent situation being that of an intrachromosomal duplication inherited from the mother. Prenatal diagnosis is performed by cytogenetic testing including FISH and/or DNA quantification methods. Management is multi-specialist and only symptomatic, with special attention to prevention of malnutrition and recurrent infections. Educational and rehabilitation support should be offered to all patients
Improved Mitochondrial Function with Diet-Induced Increase in Either Docosahexaenoic Acid or Arachidonic Acid in Membrane Phospholipids
Mitochondria can depolarize and trigger cell death through the opening of the mitochondrial permeability transition pore (MPTP). We recently showed that an increase in the long chain n3 polyunsaturated fatty acids (PUFA) docosahexaenoic acid (DHA; 22:6n3) and depletion of the n6 PUFA arachidonic acid (ARA; 20:4n6) in mitochondrial membranes is associated with a greater Ca2+ load required to induce MPTP opening. Here we manipulated mitochondrial phospholipid composition by supplementing the diet with DHA, ARA or combined DHA+ARA in rats for 10 weeks. There were no effects on cardiac function, or respiration of isolated mitochondria. Analysis of mitochondrial phospholipids showed DHA supplementation increased DHA and displaced ARA in mitochondrial membranes, while supplementation with ARA or DHA+ARA increased ARA and depleted linoleic acid (18:2n6). Phospholipid analysis revealed a similar pattern, particularly in cardiolipin. Tetralinoleoyl cardiolipin was depleted by 80% with ARA or DHA+ARA supplementation, with linoleic acid side chains replaced by ARA. Both the DHA and ARA groups had delayed Ca2+-induced MPTP opening, but the DHA+ARA group was similar to the control diet. In conclusion, alterations in mitochondria membrane phospholipid fatty acid composition caused by dietary DHA or ARA was associated with a greater cumulative Ca2+ load required to induced MPTP opening. Further, high levels of tetralinoleoyl cardiolipin were not essential for normal mitochondrial function if replaced with very-long chain n3 or n6 PUFAs
RNA chaperoning and intrinsic disorder in the core proteins of Flaviviridae
RNA chaperone proteins are essential partners of RNA in living organisms and viruses. They are thought to assist in the correct folding and structural rearrangements of RNA molecules by resolving misfolded RNA species in an ATP-independent manner. RNA chaperoning is probably an entropy-driven process, mediated by the coupled binding and folding of intrinsically disordered protein regions and the kinetically trapped RNA. Previously, we have shown that the core protein of hepatitis C virus (HCV) is a potent RNA chaperone that can drive profound structural modifications of HCV RNA in vitro. We now examined the RNA chaperone activity and the disordered nature of core proteins from different Flaviviridae genera, namely that of HCV, GBV-B (GB virus B), WNV (West Nile virus) and BVDV (bovine viral diarrhoea virus). Despite low-sequence similarities, all four proteins demonstrated general nucleic acid annealing and RNA chaperone activities. Furthermore, heat resistance of core proteins, as well as far-UV circular dichroism spectroscopy suggested that a well-defined 3D protein structure is not necessary for core-induced RNA structural rearrangements. These data provide evidence that RNA chaperoning—possibly mediated by intrinsically disordered protein segments—is conserved in Flaviviridae core proteins. Thus, besides nucleocapsid formation, core proteins may function in RNA structural rearrangements taking place during virus replication
- …