Adequate Levels of Adherence with Controller Medication Is Associated with Increased Use of Rescue Medication in Asthmatic Children

Peer reviewedPublisher PD

Synthesis and characterization of biocompatible methacrylated Kefiran hydrogels: towards tissue engineering applications

Hydrogel application feasibility is still limited mainly due to their low mechanical strength and fragile nature. Therefore, several physical and chemical cross-linking modifications are being used to improve their properties. In this research, methacrylated Kefiran was synthesized by reacting Kefiran with methacrylic anhydride (MA). The developed MA-Kefiran was physicochemically characterized, and its biological properties evaluated by different techniques. Chemical modification of MA-Kefiran was confirmed by 1H-NMR and FTIR and GPC-SEC showed an average Mw of 793 kDa (PDI 1.3). The mechanical data obtained revealed MA-Kefiran to be a pseudoplastic fluid with an extrusion force of 11.21 ± 2.87 N. Moreover, MA-Kefiran 3D cryogels were successfully developed and fully characterized. Through micro-CT and SEM, the scaffolds revealed high porosity (85.53 ± 0.15%) and pore size (33.67 ± 3.13 μm), thick pore walls (11.92 ± 0.44 μm) and a homogeneous structure. Finally, MA-Kefiran revealed to be biocompatible by presenting no hemolytic activity and an improved cellular function of L929 cells observed through the AlamarBlue® assay. By incorporating methacrylate groups in the Kefiran polysaccharide chain, a MA-Kefiran product was developed with remarkable physical, mechanical, and biological properties, resulting in a promising hydrogel to be used in tissue engineering and regenerative medicine applications.H. Radhouani and C. Goncalveswere supported by the Foundation for Science and Technology (FCT) fromPortugal, with references CEECIND/00111/2017 and SFRH/BPD/94277/2013, respectively. S. Correia and this work were funded by the R&D Project KOAT-Kefiran Exopolysaccharide: Promising Biopolymer for Use in Regenerative Medicine and Tissue Engineering, with reference PTDC/BTMMAT/29760/2017 (POCI-01-0145-FEDER-029760), financed by FCT and co-financed by FEDER and POCI. We also thank Duarte N. Carvalho for input on the schematic representation of the process

Impact of kefiran exopolysaccharide extraction on its applicability for tissue engineering and regenerative medicine

Kefiran is an exopolysaccharide produced by the microflora of kefir grains used to produce the fermented milk beverage kefir. The health-promoting and physicochemical properties of kefiran led to its exploration for a range of applications, mainly in the food industry and biomedical fields. Aiming to explore its potential for tissue engineering and regenerative medicine (TERM) applications, the kefiran biopolymer obtained through three different extraction methodologies was fully characterized and compared. High-quality kefiran polysaccharides were recovered with suitable yield through different extraction protocols. The methods consisted of heating the kefir grains prior to recovering kefiran by centrifugation and differed mainly in the precipitation steps included before lyophilization. Then, kefiran scaffolds were successfully produced from each extract by cryogelation and freeze-drying. In all extracts, it was possible to identify the molecular structure of the kefiran polysaccharide through 1H-NMR and FTIR spectra. The kefiran from extraction 1 showed the highest molecular weight (~3000 kDa) and the best rheological properties, showing a pseudoplastic behavior; its scaffold presented the highest value of porosity (93.2% ± 2), and wall thickness (85.8 µm ± 16.3). All extracts showed thermal stability, good injectability and desirable viscoelastic properties; the developed scaffolds demonstrated mechanical stability, elastic behavior, and pore size comprised between 98â 94 µm. Additionally, all kefiran products proved to be non-cytotoxic over L929 cells. The interesting structural, physicochemical, and biological properties showed by the kefiran extracts and cryogels revealed their biomedical potential and suitability for TERM applications.H. Radhouani and C. Gonçalves were supported by the Foundation for Science and Technology (FCT) from Portugal, with references CEECIND/00111/2017 and SFRH/BPD/94277/ 2013, respectively. S. Correia and this work were funded by the R&D Project KOAT—Kefiran Exopolysaccharide: Promising Biopolymer for Use in Regenerative Medicine and Tissue Engineering, with reference PTDC/BTMMAT/29760/2017 (POCI-01-0145-FEDER-029760), financed by FCT and co-financed by FEDER and POCI, and by the Project “HEALTH-UNORTE: Setting-up biobanks and regenerative medicine strategies to boost research in cardiovascular, musculoskeletal, neurological, oncological, immunological and infectious diseases”, ref. NORTE-01-0145-FEDER-000039 funded under the program NORTE-45-2020-20—Sistema de Apoio à Investigação Científica e Tecnológica— “Projetos Estruturados de I&D&I” UNorte. We also thank Duarte N. Carvalho for input on the schematic representation of the process

‘When I look at this van, it’s not only a van’: symbolic objects in the policing of migration

The ‘Go Home Van’ was the centrepiece of the UK government’s 2013 immigration enforcement campaign. Vehicles were driven around ethnically diverse London neighbourhoods clad with giant posters offering irregular migrants a choice between ‘voluntary departure’ and criminal arrest. Abandoned shortly afterwards in response to complaints, the GHV nonetheless had a significant impact on migrants. Through interviews and focus groups, this article investigates what was conveyed by the van, and the means by which it achieved these effects. We find that the GHV communicated meanings about the illegitimacy and criminality of migrants, with its material characteristics (visibility and mobility) as important as the words and pictures on its surface. Migrants sought to resist the van through hiding, while support organisations rejected dominant meanings and crafted alternatives. The article establishes a research agenda around the wider role of symbolic objects, in the context of the global migration crisis

A general wavelet-based profile decomposition in the critical embedding of function spaces

We characterize the lack of compactness in the critical embedding of functions spaces $X\subset Y$ having similar scaling properties in the following terms : a sequence $(u_n)_{n\geq 0}$ bounded in $X$ has a subsequence that can be expressed as a finite sum of translations and dilations of functions $(\phi_l)_{l>0}$ such that the remainder converges to zero in $Y$ as the number of functions in the sum and $n$ tend to $+\infty$. Such a decomposition was established by G\'erard for the embedding of the homogeneous Sobolev space $X=\dot H^s$ into the $Y=L^p$ in $d$ dimensions with $0<s=d/2-d/p$, and then generalized by Jaffard to the case where $X$ is a Riesz potential space, using wavelet expansions. In this paper, we revisit the wavelet-based profile decomposition, in order to treat a larger range of examples of critical embedding in a hopefully simplified way. In particular we identify two generic properties on the spaces $X$ and $Y$ that are of key use in building the profile decomposition. These properties may then easily be checked for typical choices of $X$ and $Y$ satisfying critical embedding properties. These includes Sobolev, Besov, Triebel-Lizorkin, Lorentz, H\"older and BMO spaces.Comment: 24 page

Development of conjugated kefiran-chondroitin sulphate cryogels with enhanced properties for biomedical applications

Hydrogels based on natural polysaccharides can have unique properties and be tailored for several applications, which may be mainly limited by the fragile structure and weak mechanical properties of this type of system. We successfully prepared cryogels made of newly synthesized kefiran exopolysaccharide-chondroitin sulfate (CS) conjugate via carbodiimide-mediated coupling to overcome these drawbacks. The freeze-thawing procedure of cryogel preparation followed by lyophilization is a promising route to fabricate polymer-based scaffolds with countless and valuable biomedical applications. The novel graft macromolecular compound (kefiran-CS conjugate) was characterized through 1H-NMR and FTIR spectroscopy—which confirmed the structure of the conjugate, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)—which mirrored good thermal stability (degradation temperature of about 215 °C) and, finally, gel permeation chromatography–size exclusion chromatography (GPC-SEC)—which proved an increased molecular weight due to chemical coupling of kefiran with CS. At the same time, the corresponding cryogels physically crosslinked after the freeze-thawing procedure were investigated by scanning electron microscopy (SEM), Micro-CT, and dynamic rheology. The results revealed a prevalent contribution of elastic/storage component to the viscoelastic behavior of cryogels in swollen state, a micromorphology with micrometer-sized open pores fully interconnected, and high porosity (ca. 90%) observed for freeze-dried cryogels. Furthermore, the metabolic activity and proliferation of human adipose stem cells (hASCs), when cultured onto the developed kefiran-CS cryogel, was maintained at a satisfactory level over 72 h. Based on the results obtained, it can be inferred that the newly freeze-dried kefiran-CS cryogels possess a host of unique properties that render them highly suitable for use in tissue engineering, regenerative medicine, drug delivery, and other biomedical applications where robust mechanical properties and biocompatibility are crucial.This research was funded by the Foundation for Science and Technology (FCT) from Portugal, with references CEECIND/00111/2017 and SFRH/BPD/94277/2013, respectively.H.R. and C.G. were supported by the Foundation for Science and Technology (FCT) from Portugal, with references CEECIND/00111/2017 and SFRH/BPD/94277/2013, respectively. The authors would like to express their sincere gratitude to Emanuel Fernandes for his invaluable contribution to this research by performing the STA experiment. The authors thank the financial support provided under the project “HEALTH-UNORTE: Setting-up biobanks and regenerative medicine strategies to boost research in cardiovascular, musculoskeletal, neurological, oncological, immunological and infectious diseases”, reference NORTE-01-0145-FEDER-000039, funded by the Norte Portugal Regional Coordination and Development Commission (CCDR-N), under the NORTE2020 Program

Problematizing Choice: Responsible consumers and sceptical citizens

About the book: Governance, Consumers and Citizens is the first book to bring together a study of governance with consumption, examining the changing place of the consumer as citizen in recent trends in governance, the tensions between competing ideas and practices of consumerism and the active role consumers play in the construction and practice of governance. Radically pushing forward the debate on consumers and governance, this collection outlines new conceptions and posits new policy agendas. Bringing together international experts from political science, history, geography, social policy and media studies, this study shows how governance and consumption are intertwined in crucial aspects of public policy and contemporary politics

Antagonism of the Azoles to Olorofim and Cross-Resistance Are Governed by Linked Transcriptional Networks in Aspergillus fumigatus

Aspergillosis, in its various manifestations, is a major cause of morbidity and mortality. Very few classes of antifungal drugs have been approved for clinical use to treat these diseases and resistance to the first-line therapeutic class, the triazoles are increasing. A new class of antifungals that target pyrimidine biosynthesis, the orotomides, are currently in development with the first compound in this class, olorofim in late-stage clinical trials. In this study, we identified an antagonistic action of the triazoles on the action of olorofim. We showed that this antagonism was the result of an azole-induced upregulation of the pyrimidine biosynthesis pathway. Intriguingly, we showed that loss of function in the higher order transcription factor, HapB a member of the heterotrimeric HapB/C/E (CBC) complex or the regulator of nitrogen metabolic genes AreA, led to cross-resistance to both the azoles and olorofim, indicating that factors that govern resistance were under common regulatory control. However, the loss of azole-induced antagonism required decoupling of the pyrimidine biosynthetic pathway in a manner independent of the action of a single transcription factor. Our study provided evidence for complex transcriptional crosstalk between the pyrimidine and ergosterol biosynthetic pathways. IMPORTANCE: Aspergillosis is a spectrum of diseases and a major cause of morbidity and mortality. To treat these diseases, there are a few classes of antifungal drugs approved for clinical use. Resistance to the first line treatment, the azoles, is increasing. The first antifungal, olorofim, which is in the novel class of orotomides, is currently in development. Here, we showed an antagonistic effect between the azoles and olorofim, which was a result of dysregulation of the pyrimidine pathway, the target of olorofim, and the ergosterol biosynthesis pathway, the target of the azoles.This work was supported by the Wellcome Trust grant number 219551/Z/19/Z and 208396/Z/17/Z to M.J.B. C.V. was funded by a postdoctoral fellowship from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP-BEPE 2020/01131-5).S

Recycling bins, garbage cans or think tanks? Three myths regarding policy analysis institutes

The phrase 'think tank' has become ubiquitous – overworked and underspecified – in the political lexicon. It is entrenched in scholarly discussions of public policy as well as in the 'policy wonk' of journalists, lobbyists and spin-doctors. This does not mean that there is an agreed definition of think tank or consensual understanding of their roles and functions. Nevertheless, the majority of organizations with this label undertake policy research of some kind. The idea of think tanks as a research communication 'bridge' presupposes that there are discernible boundaries between (social) science and policy. This paper will investigate some of these boundaries. The frontiers are not only organizational and legal; they also exist in how the 'public interest' is conceived by these bodies and their financiers. Moreover, the social interactions and exchanges involved in 'bridging', themselves muddy the conception of 'boundary', allowing for analysis to go beyond the dualism imposed in seeing science on one side of the bridge, and the state on the other, to address the complex relations between experts and public policy

Opening up animal research and science-society relations?: a thematic analysis of transparency discourses in the United Kingdom

The use of animals in scientific research represents an interesting case to consider in the context of the contemporary preoccupation with transparency and openness in science and governance. In the United Kingdom, organisations critical of animal research have long called for more openness. More recently, organisations involved in animal research also seem to be embracing transparency discourses. This article provides a detailed analysis of publically available documents from animal protection groups, the animal research community and government/research funders. Our aim is to explore the similarities and differences in the way transparency is constructed and to identify what more openness is expected to achieve. In contrast to the existing literature, we conclude that the slipperiness of transparency discourses may ultimately have transformative implications for the relationship between science and society and that contemporary openness initiatives might be sowing the seeds for change to the status quo