269 research outputs found

    Post-Transcriptional Dysregulation by miRNAs Is Implicated in the Pathogenesis of Gastrointestinal Stromal Tumor [GIST]

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    peer-reviewedIn contrast to adult mutant gastrointestinal stromal tumors [GISTs], pediatric/wild-type GISTs remain poorly understood overall, given their lack of oncogenic activating tyrosine kinase mutations. These GISTs, with a predilection for gastric origin in female patients, show limited response to therapy with tyrosine kinase inhibitors and generally pursue a more indolent course, but still may prove fatal. Defective cellular respiration appears to underpin tumor development in these wild-type cases, which as a group lack expression of succinate dehydrogenase [SDH] B, a surrogate marker for respiratory chain metabolism. Yet, only a small subset of the wild-type tumors show mutations in the genes coding for the SDH subunits [SDHx]. To explore additional pathogenetic mechanisms in these wild-type GISTs, we elected to investigate posttranscriptional regulation of these tumors by conducting microRNA (miRNA) profiling of a mixed cohort of 73 cases including 18 gastric pediatric wild-type, 25 (20 gastric, 4 small bowel and 1 retroperitoneal) adult wild-type GISTs and 30 gastric adult mutant GISTs. By this approach we have identified distinct signatures for GIST subtypes which correlate tightly with clinico-pathological parameters. A cluster of miRNAs on 14q32 show strikingly different expression patterns amongst GISTs, a finding which appears to be explained at least in part by differential allelic methylation of this imprinted region. Small bowel and retroperitoneal wild-type GISTs segregate with adult mutant GISTs and express SDHB, while adult wildtype gastric GISTs are dispersed amongst adult mutant and pediatric wild-type cases, clustering in this situation on the basis of SDHB expression. Interestingly, global methylation analysis has recently similarly demonstrated that these wild-type, SDHB-immunonegative tumors show a distinct pattern compared with KIT and PDGFRA mutant tumors, which as a rule do express SDHB. All cases with Carney triad within our cohort cluster together tightly.Funding was obtained from the Medical Research Charities Group (http://www.mrcg.ie/) and Health Research Board of Ireland (http://www.hrb.ie) (MO’S), The Children’s Medical and Research Foundation (http://www.cmrf.org) (MO’S), the GIST Cancer Awareness Foundation [GCAF] (http://www. gistawareness.org/)(MO’S), and research grants from the Life Raft Group (http://www.liferaftgroup.org/)(MD-R) and from the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (http://www.fwo.be/)(grant # G.0286.05 MD-R)

    To dine in or not to dine in: A comparison of food selection and preparation behaviours in those with and without food security

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    © 2020 The Authors. Health Promotion Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of Australian Health Promotion Association Issue addressed: Vulnerable populations are disproportionately affected by food insecurity, resulting in heightened risk of suboptimal dietary intake. Food insecure people appear to implement several coping strategies and dietary compromises to avoid hunger. Less explored in the literature is how these strategies impact consumption of food inside and outside of the home. Methods: An online survey was completed by adults (n = 1292) residing in one of five Australian states. The questionnaire comprised of the six-item US Household Food Security Survey Module, 12 socio-demographic variables and 32 questions related to elements of food literacy. Results: Food insecure respondents were more likely to frequent fast food vs (P =.002), takeaway (P \u3c .001) and food courts (P \u3c .001) than their food secure counterparts. Food secure respondents reported greater use of raw (P =.043) and fresh, pre-prepared produce (P =.002) when cooking, whereas food insecure respondents were more likely to prepare food using only frozen, pre-packaged products (P \u3c .001). No significant differences were found between food security status and the enjoyment and social bonding derived from cooking. Conclusions: Food insecure respondents appeared to be accessing a poorer quality of food through greater consumption of takeaway and fast food. These dietary compromises are most likely related to perceived financial, time or cooking facility constraints and to a lesser extent food literacy skills. So what?: This study highlights some of the health and social inequities apparent within food insecure populations. Food insecure households should be supported to access healthy fresh food and in-home cooking practices. While a multi strategy approach is required, healthy food environment policy, particularly in disadvantaged areas, should be considered to guarantee that all Australians have dignified access to nutritious food

    Australian consumers are willing to pay for the health star rating front-of-pack nutrition label

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    © 2020 by the authors. Licensee MDPI, Basel, Switzerland. The Australia and New Zealand Ministerial Forum on Food Regulation has supported the recommendations set out in the 2019 Health Star Rating System Five Year Review Report. Specifically, the forum supported, in principle, Recommendation 9, to mandate the Health Star Rating if clear uptake targets were not achieved while the system is voluntary. Given that mandatory labelling is being considered, it is important to investigate how much consumers value the Health Star Rating in order to understand potential consumer uptake and inform industry. The aim of this study was to assess consumers’ valuation of the Health Star Rating system by analysing their willingness to pay for a packaged food product with the Health Star Rating label, utilising a double-bounded dichotomous choice contingent valuation approach. The results indicate that almost two-thirds of Australian household grocery shoppers were willing to pay more for a product with the Health Star Rating, on average up to an additional 3.7% of the price of the product. However, public health nutrition benefits associated with consumers’ willingness to pay more for products with the Health Star Rating is currently limited by the lack of guarantee of the systems’ accuracy. Given consumer support, a well validated and comprehensive Health Star Rating labelling system can potentially improve health outcomes, cost effectiveness and reduce environmental impacts

    Height dependent molecular trapping in stacked cyclic porphyrin nanorings

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    Stacked layers of cyclic porphyrin nanorings constitute nanoscale receptacles with variable height and diameter which preferentially adsorb sublimed molecules. Using scanning tunnelling microscopy we determine the filling capacity of these nanoring traps, and the dependence of adsorbate capture on stack height and diameter

    Grey matter volume alterations in CADASIL: a voxel-based morphometry study

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    CADASIL is a hereditary disease characterized by cerebral subcortical microangiopathy leading to early onset cerebral strokes and progressive severe cognitive impairment. Until now, only few studies have investigated the extent and localization of grey matter (GM) involvement. The purpose of our study was to evaluate GM volume alterations in CADASIL patients compared to healthy subjects. We also looked for correlations between global and regional white matter (WM) lesion load and GM volume alterations. 14 genetically proved CADASIL patients and 12 healthy subjects were enrolled in our study. Brain MRI (1.5 T) was acquired in all subjects. Optimized-voxel based morphometry method was applied for the comparison of brain volumes between CADASIL patients and controls. Global and lobar WM lesion loads were calculated for each patient and used as covariate-of-interest for regression analyses with SPM-8. Compared to controls, patients showed GM volume reductions in bilateral temporal lobes (p < 0.05; FDR-corrected). Regression analysis in the patient group revealed a correlation between total WM lesion load and temporal GM atrophy (p < 0.05; uncorrected), not between temporal lesion load and GM atrophy. Temporal GM volume reduction was demonstrated in CADASIL patients compared to controls; it was related to WM lesion load involving the whole brain but not to lobar and, specifically, temporal WM lesion load. Complex interactions between sub-cortical and cortical damage should be hypothesized

    Visions for a walking and cycling focussed urban transport system

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    Walking and cycling can make a considerable contribution to sustainable transport goals, building healthier and more sustainable communities and contributing to traffic and pollution reduction. There have been many national and local initiatives to promote walking and cycling, but without a long term vision and consistent strategy it is difficult to see how a significant change may be achieved. This paper presents three alternative visions for the role of walking and cycling in urban areas for the year 2030: each vision illustrates a ‘desirable’ walking- and cycling-oriented transport system against a different ‘exogenous social background’. These visions have been developed through a process of expert discussion and review and are intended to provide a stimulus for debate on the potential for and desirability of such alternative futures. Each is based on the UK and represents a substantial change to the current situation: in particular, each of the visions presents a view of a society where walking and cycling are considerably more important than is currently the case and where these modes cater for a much higher proportion of urban transport needs than at present. The visions show pictures of urban environments where dependence on motor vehicles has been reduced, in two of the visions to very low levels. The methodological approach for devising visions is informed by work on ‘utopian thinking’: a key concept underlying this approach is one of viewing the future in social constructivist terms (i.e. the future is what ‘we’, as a society, make it) rather than considering the future as something that can be ‘scientifically’ predicted by the extrapolation of current trends

    Human CD56(dim)CD16(dim) Cells As an Individualized Natural Killer Cell Subset

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    ABSTARCT: Human natural killer (NK) cells can be subdivided in several subpopulations on the basis of the relative expression of the adhesion molecule CD56 and the activating receptor CD16. Whereas blood CD56brightCD16dim/- NK cells are classically viewed as immature precursors and cytokine producers, the larger CD56dimCD16bright subset is considered as the most cytotoxic one. In peripheral blood of healthy donors, we noticed the existence of a population of CD56dimCD16dim NK cells that was frequently higher in number than the CD56bright subsets and even expanded in occasional control donors but also in transporter associated with antigen processing-deficient patients, two familial hemophagocytic lymphohistiocytosis type II patients, and several common variable immunodeficiency patients. This population was detected but globally reduced in a longitudinal cohort of 18 HIV-1-infected individuals. Phenotypically, the new subset contained a high percentage of relatively immature cells, as reflected by a significantly stronger representation of NKG2A+ and CD57- cells compared to their CD56dimCD16bright counterparts. The phenotype of the CD56dimCD16dim population was differentially affected by HIV-1 infection as compared to the other NK cell subsets and only partly restored to normal by antiretroviral therapy. From the functional point of view, sorted CD56dimCD16dim cells degranulated more than CD56dimCD16bright cells but less than CD56dimCD16- NK cells. The population was also identified in various organs of immunodeficient mice with a human immune system ("humanized" mice) reconstituted from human cord blood stem cells. In conclusion, the CD56dimCD16dim NK cell subpopulation displays distinct phenotypic and functional features. It remains to be clarified if these cells are the immediate precursors of the CD56dimCD16bright subset or placed somewhere else in the NK cell differentiation and maturation pathway

    Innovative multi-site photoplethysmography measurement and analysis demonstrating increased arterial stiffness in paediatric heart transplant recipients

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    Objective: It has been documented that heart transplantation in children is often complicated by arterial hypertension and increased arterial stiffness. We use innovative multi-site photoplethysmography (MPPG) pulse measurement and analysis technology to assess changes in arterial stiffness in paediatric heart transplant recipients (HTRs) in comparison with healthy control (HC) children. Approach: A group of 20 HTRs (median age 13.5 years, eight male) were compared to an overall age- and gender-matched group of 161 HCs (median age 11.6 years, 74 male). Peripheral pulse was recorded bilaterally using MPPG at the ear lobe, index finger and great toe sites, along with an electrocardiogram cardiac timing reference. Segmental pulse arrival times between peripheral sites (finger–ear, PATf–e; toe–finger, PATt–f; and toe–ear PATt–e) were calculated as arterial stiffness measures, and differences between subject groups were tested using multivariate analysis. Normalised ear, finger and toe pulse shapes were also studied and compared between groups. Main results: After correction for heart rate and diastolic and mean arterial blood pressures, the HTR group was found to have significantly lower segmental PATt–e and PATt–f measurements, with median values of 150 ms versus 172 ms in the HC group (p  =  0.02), and 104 ms versus 118 ms in the HC group (p  =  0.01), respectively, consistent with increased arterial stiffness in the patient group. The normalised ear, finger and toe sites showed only a mild elongation in each pulse rise time for the transplant group. Significance: This study shows that innovative and easy-to-do MPPG gives further evidence for increased arterial stiffness in children who have undergone successful cardiac transplantation

    QUBIC VIII: Optical design and performance

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    The Q and U Bolometric Interferometer for Cosmology (QUBIC) is a ground-based experiment that aims to detect B-mode polarization anisotropies [1] in the CMB at angular scales around the â.,"≃100 recombination peak. Systematic errors make ground-based observations of B modes at millimetre wavelengths very challenging and QUBIC mitigates these problems in a somewhat complementary way to other existing or planned experiments using the novel technique of bolometric interferometry. This technique takes advantage of the sensitivity of an imager and the systematic error control of an interferometer. A cold reflective optical combiner superimposes the re-emitted beams from 400 aperture feedhorns on two focal planes. A shielding system composed of a fixed groundshield, and a forebaffle that moves with the instrument, limits the impact of local contaminants. The modelling, design, manufacturing and preliminary measurements of the optical components are described in this paper.Fil: O’Sullivan, C.. National University Of Ireland Galway.; IrlandaFil: De Petris, M.. Università di Roma; Italia. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Amico, G.. Università di Roma; ItaliaFil: Battistelli, E. S.. Università di Roma; Italia. Istituto Nazionale di Fisica Nucleare; ItaliaFil: De Bernardis, P.. Università di Roma; Italia. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Burke, D.. National University of Ireland Galway; IrlandaFil: Buzi, D.. Università di Roma; ItaliaFil: Chapron, C.. Centre National de la Recherche Scientifique; FranciaFil: Conversi, L.. European Space Agency; ItaliaFil: D’Alessandro, G.. Università di Roma; Italia. Istituto Nazionale di Fisica Nucleare; ItaliaFil: De Leo, M.. Università di Roma; Italia. University of Surrey; Reino UnidoFil: Almela, Daniel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Cobos Cerutti, Agustin Cleto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Duca, Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Etchegoyen, Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Ferreyro, Luciano Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Fracchia, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Gamboa Lerena, Martín Miguel. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Garcia, Beatriz Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: García Redondo, Manuel Elías. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Gervasi, Maria Gracia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Università degli Studi di Milano; Italia. Istituto Nazionale di Fisica Nucleare; ItaliaFil: Gomez Berisso, Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Hampel, Matias Rolf. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Harari, Diego Dario. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Melo, Diego Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Platino, Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Romero, Gustavo Esteban. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Salum, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Supanitsky, Alberto Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Wright, María. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Manchester; Reino Unid
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