723 research outputs found

    Global patterns in students’ views of science and interest in science

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    This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.International studies have shown that interest in science and technology among primary and secondary school students in Western European countries is low and seems to be decreasing. In many countries outside Europe, and especially in developing countries, interest in science and technology remains strong. As part of the large-scale European Union funded ‘Science Education for Diversity’ project, a questionnaire probing potential reasons for this difference was completed by students in the UK, Netherlands, Turkey, Lebanon, India and Malaysia. This questionnaire sought information about favourite courses, extracurricular activities and views on the nature of science. Over 9,000 students aged mainly between 10 and 14 years completed the questionnaire. Results revealed that students in countries outside Western Europe showed a greater interest in school science, in careers related to science and in extracurricular activities related to science than didWestern European students. Non-European studentswere also more likely to hold an empiricist viewof the nature of science and to believe that science can solve many problems faced by the world. Multilevel analysis revealed a strong correlation between interest in science and having such a view of the Nature of Science.This publication received funding from the European Union Science in Society Framework 7 Programme (FP7/2007/2013) under grant agreement 244717. We would like to thank the following people for collecting data and contributing to this research project: Roel Janssen, Huseyin Bag, Lindsay Hetherington, Alun Morgan, Keith Postlethwaite, Rupert Wegerif, Ng Swee Chin, Choy Siew Chee, Oo Pou San, Chin Fui Chung, Teh Lee Wah, Sugra Chunawala, Chitra Natarajan and Beena Chok

    Therapeutic effects of co-inhaled roflumilast or formoterol and fluticasone on asthma-induced ultrastructural changes in murine airways

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    Purpose: To investigate the therapeutic effects of "inhaled" roflumilast and formoterol separately or combined with fluticasone on the ultrastructural airway changes in ovalbumin-induced asthmatic mice.Methods: The asthmatic mice were divided randomly into seven groups (n = 8): positive control, vehicle, and five treated groups. The following treatments were given by inhalation (15 min once/day) for seven days: roflumilast (500 μg/kg), formoterol (50 μg/kg), fluticasone (1000 μg/kg), roflumilast + fluticasone (500 + 1000 μg/kg), and formoterol + fluticasone (50 + 1000 μg/kg). Ultrathin lung sections (50 - 70 nm thick) were examined by transmission electron microscopy.Results: The asthmatic mice showed marked degenerative changes in bronchiolar epithelial cells. The alveolar septal walls were thickened with cellular changes and capillary congestion. The basement membranes showed marked thickening and the airway lumens contained abundant mucinous secretions. These ovalbumin-induced ultrastructural airway changes were markedly-reversed in the roflumilast + fluticasone group, moderately-reversed in the roflumilast, fluticasone, and formoterol + fluticasone groups, but were not affected in the formoterol group.Conclusion: Co-inhalation of roflumilast + fluticasone significantly improved the ultrastructural airway changes than co-inhalation of formoterol + fluticasone in ovalbumin-asthmatic mice due to its antiinflammatory and antifibrotic effects.Keywords: Asthma, Fluticasone Propionate, Formoterol, Roflumilast, Ovalbumin, Remodeling, Bronchiolar epitheliu

    Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci.

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    Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals born in Denmark since 1981 and diagnosed with schizophrenia as well as controls from the same birth cohort. Furthermore, we present the first genome-wide interaction survey of single nucleotide polymorphisms (SNPs) and maternal cytomegalovirus (CMV) infection. The GWA analysis included 888 cases and 882 controls, and the follow-up investigation of the top GWA results was performed in independent Danish (1396 cases and 1803 controls) and German-Dutch (1169 cases, 3714 controls) samples. The SNPs most strongly associated in the single-marker analysis of the combined Danish samples were rs4757144 in ARNTL (P=3.78 × 10(-6)) and rs8057927 in CDH13 (P=1.39 × 10(-5)). Both genes have previously been linked to schizophrenia or other psychiatric disorders. The strongest associated SNP in the combined analysis, including Danish and German-Dutch samples, was rs12922317 in RUNDC2A (P=9.04 × 10(-7)). A region-based analysis summarizing independent signals in segments of 100 kb identified a new region-based genome-wide significant locus overlapping the gene ZEB1 (P=7.0 × 10(-7)). This signal was replicated in the follow-up analysis (P=2.3 × 10(-2)). Significant interaction with maternal CMV infection was found for rs7902091 (P(SNP × CMV)=7.3 × 10(-7)) in CTNNA3, a gene not previously implicated in schizophrenia, stressing the importance of including environmental factors in genetic studies

    Brazilian Guidelines for Hereditary Angioedema Management - 2017 Update Part 1: Definition, Classification and Diagnosis

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    Hereditary angioedema is an autosomal dominant disease characterized by recurrent angioedema attacks with the involvement of multiple organs. The disease is unknown to many health professionals and is therefore underdiagnosed. Patients who are not adequately diagnosed and treated have an estimated mortality rate ranging from 25% to 40% due to asphyxiation by laryngeal angioedema. Intestinal angioedema is another important and incapacitating presentation that may be the main or only manifestation during an attack. In this article, a group of experts from the “Associação Brasileira de Alergia e Imunologia (ASBAI)” and the “Grupo de Estudos Brasileiro em Angioedema Hereditário (GEBRAEH)” has updated the Brazilian guidelines for the diagnosis and treatment of hereditary angioedema

    Goldberg-Shprintzen syndrome is determined by the absence, or reduced expression levels, of KIFBP.

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    Goldberg-Shprintzen syndrome (GOSHS) is caused by loss of function variants in the kinesin binding protein gene (KIFBP). However, the phenotypic range of this syndrome is wide, indicating that other factors may play a role. To date, 37 patients with GOSHS have been reported. Here, we document nine new patients with variants in KIFBP: seven with nonsense variants and two with missense variants. To our knowledge, this is the first time that missense variants have been reported in GOSHS. We functionally investigated the effect of the variants identified, in an attempt to find a genotype-phenotype correlation. We also determined whether common Hirschsprung disease (HSCR)-associated single nucleotide polymorphisms (SNPs), could explain the presence of HSCR in GOSHS. Our results showed that the missense variants led to reduced expression of KIFBP, while the truncating variants resulted in lack of protein. However, no correlation was found between the severity of GOSHS and the location of the variants. We were also unable to find a correlation between common HSCR-associated SNPs, and HSCR development in GOSHS. In conclusion, we show that reduced, as well as lack of KIFBP expression can lead to GOSHS, and our results suggest that a threshold expression of KIFBP may modulate phenotypic variability of the disease

    Fyn Mediates Leptin Actions in the Thymus of Rodents

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    BACKGROUND:Several effects of leptin in the immune system rely on its capacity to modulate cytokine expression and apoptosis in the thymus. Surprisingly, some of these effects are dependent on signal transduction through the IRS1/PI3-kinase, but not on the activation of JAK2. Since all the well known effects of leptin in different cell types and tissues seem to be dependent on JAK2 activation, we hypothesized that, at least for the control of thymic function, another, unknown kinase could mediate the transduction of the leptin signal from the ObR towards the IRS1/PI3-kinase signaling cascade. METHODOLOGY/PRINCIPAL FINDINGS:Here, by employing immunoblot, real-time PCR and flow citometry we show that the tyrosine kinase, Fyn, is constitutively associated with the ObR in thymic cells. Following a leptin stimulus, Fyn undergoes an activating tyrosine phosphorylation and a transient association with IRS1. All these effects are independent of JAK2 activation and, upon Fyn inhibition, the signal transduction towards IRS1/PI3-kinase is abolished. In addition, the inhibition of Fyn significantly modifies the effects of leptin on thymic cytokine expression. CONCLUSION/SIGNIFICANCE:Therefore, in the thymus, Fyn acts as a tyrosine kinase that transduces the leptin signal independently of JAK2 activation, and mediates some of the immunomodulatory effects of leptin in this tissue

    Diabetes mellitus type 2 and other chronic non-communicable diseases in the central region, Saudi Arabia (riyadh cohort 2): a decade of an epidemic

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    <p>Abstract</p> <p>Background</p> <p>Follow-up epidemiologic studies are needed to assess trends and patterns of disease spread. No follow-up epidemiologic study has been done in the Kingdom of Saudi Arabia to assess the current prevalence of major chronic, noncommunicable diseases, specifically in the urban region, where modifiable risk factors remain rampant. This study aims to fill this gap.</p> <p>Methods</p> <p>A total of 9,149 adult Saudis ages seven to eighty years (5,357 males (58.6%) and 3,792 females (41.4%)) were randomly selected from the Riyadh Cohort Study for inclusion. Diagnosis of type 2 diabetes mellitus (DMT2) and obesity were based on the World Health Organization definitions. Diagnoses of hypertension and coronary artery disease (CAD) were based on the Seventh Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure and American Heart Association criteria, respectively.</p> <p>Results</p> <p>The overall crude prevalence of DMT2 was 23.1% (95% confidence interval (95% CI) 20.47 to 22.15). The age-adjusted prevalence of DMT2 was 31.6%. DMT2 prevalence was significantly higher in males, with an overall age-adjusted prevalence of 34.7% (95% CI 32.6 to 35.4), than in females, who had an overall age-adjusted prevalence of 28.6% (95% CI 26.7 to 29.3) (<it>P </it>< 0.001). The overall crude prevalence of obesity was 31.1% (95% CI 30.1 to 32.0). The age-adjusted prevalence of obesity was 40.0%. The prevalence of obesity was higher in females, with an overall prevalence of 36.5% (95% CI 35.1 to 37.83), than in males (25.1% (95% CI 23.7 to 26.3)) (<it>P </it>< 0.001). The age-adjusted prevalence of hypertension and CAD were 32.6% (95% CI 31.7 to 33.6) and 6.9% (95% CI 6.4 to 7.4), respectively.</p> <p>Conclusion</p> <p>Comparisons of our findings with earlier data show that the prevalence of DMT2, hypertension and CAD in Riyadh, Saudi Arabia, has alarmingly worsened. Aggressive promotion of public awareness, continued screening and early intervention are pivotal to boosting a positive response.</p

    Serum CEA and CA 15-3 as prognostic factors in primary breast cancer

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    In the present study, we investigated the association of the serum levels of the tumour markers carcinoembryonic antigen and cancer antigen 15-3 with disease free survival and death from disease in 1046 women with breast cancer without metastases at the time of primary diagnosis in relation to age and the established prognostic factors tumour size, lymph node status, histological grading and hormone receptor status. We found that elevated pre-operative serum marker values were correlated with early relapse (cancer antigen 15-3; P=0.0003) and death from disease (carcinoembryonic antigen, cancer antigen 15-3; P=0.0001 both) in univariate analyses. By comparing pre- and post-operative values we found a decline in values post-surgery. In those patients where marker levels of carcinoembryonic antigen decreased more than 33%, a significantly higher risk for relapse and death from disease (both P=0.0001) in univariate analyses was observed. In multivariate analysis this decrease of carcinoembryonic antigen proved to be an independent prognostic factor. The results for cancer antigen 15-3 were comparable to carcinoembryonic antigen in univariate analyses but showed no significance in multivariate analysis. In this study the post-operative decrease of the serum tumour marker carcinoembryonic antigen was a strong independent prognostic factor for disease free survival and death from disease in breast cancer patients

    Formulation of Biologically-Inspired Silk-Based Drug Carriers for Pulmonary Delivery Targeted for Lung Cancer

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    The benefits of using silk fibroin, a major protein in silk, are widely established in many biomedical applications including tissue regeneration, bioactive coating and in vitro tissue models. The properties of silk such as biocompatibility and controlled degradation are utilized in this study to formulate for the first time as carriers for pulmonary drug delivery. Silk fibroin particles are spray dried or spray-freeze-dried to enable the delivery to the airways via dry powder inhalers. The addition of excipients such as mannitol is optimized for both the stabilization of protein during the spray-freezing process as well as for efficient dispersion using an in vitro aerosolisation impactor. Cisplatin is incorporated into the silk-based formulations with or without cross-linking, which show different release profiles. The particles show high aerosolisation performance through the measurement of in vitro lung deposition, which is at the level of commercially available dry powder inhalers. The silk-based particles are shown to be cytocompatible with A549 human lung epithelial cell line. The cytotoxicity of cisplatin is demonstrated to be enhanced when delivered using the cross-linked silk-based particles. These novel inhalable silk-based drug carriers have the potential to be used as anti-cancer drug delivery systems targeted for the lungs
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