Off-label prescribing for allergic diseases in pre-school children

BACKGROUND: Several studies have demonstrated that medication is commonly used off-label in children with allergic diseases. The aim of this study was to characterise off-label use of prescriptions for allergic diseases in pre-school children from an allergology outpatient unit. METHODS: The clinical files of children aged ≤6 years seen in a reference allergology consultation with asthma, allergic rhinitis, and/or atopic eczema were reviewed. A total of 500 patients were consecutively observed from January to June 2012. The data collected included gender, age, diagnosis, and prescriptions with the respective daily dosage. RESULTS: A total of 1224 prescriptions were registered. The most prescribed medications were oral antihistamines (34.6%), antileukotrienes (22.6%), topical nasal corticosteroids (20.3%), and inhaled corticosteroids (17.7%). From all prescriptions, 422 (34.5%) were considered off-label for age (62.6%), dosage (31.7%), or clinical indication (5.7%). Off-label use was more frequent in children aged <2 years, with 73.5% prescribed for children of this age. CONCLUSIONS: Off-label use of drugs for the treatment of paediatric allergic diseases is high. However, these prescriptions are not necessarily wrong, and are recommended in many guidelines. Randomised controlled studies are limited by methodological difficulties creating the need for more observational studies in order to further evaluate the safety and efficacy of drugs used in children

Melanoma brain metastases presenting as delirium: a case report

info:eu-repo/semantics/publishedVersio

Cardiocerebral Infarction: A Combination to Prevent

Sources of Funding There were no external funding sources for this study.Background The acute complications of myocardial infarction (MI), such as mechanical, arrhythmic, ischemic, and inflammatory sequelae, may be responsible for significant cardiovascular morbimortality. Life-threatening arrhythmias, namely ventricular fibrillation or tachycardia, may be a challenging complication requiring a prompt approach. In some cases, acute ischemia leads to polymorphic ventricular tachycardia (PVT), and, rarely, to potentially lethal torsades de pointes ventricular tachycardia.info:eu-repo/semantics/publishedVersio

Structural studies on two lipocalins

The number of proteins being included in the lipocalin structural family has been steadily increasing since the solution of the structures of beta -lactoglobulin and retinol- binding protein. The family now comprises some 23 proteins and these come from many different sources and display a variety of characteristics. The work described here focused on two of those proteins, beta -lactoglobulin (Big) and apolipoprotein D (apo D).The structure of bovine beta -lactoglobulin (Monaco, et al., 1987)from the trigonal crystals grown at pH 7.8, space group P3221, presents several aspects that are in disagreement with previous work, in particular the positioning of the bound retinol in the surface of the protein and the observation that the protein was in its monomeric form. We have checked these findings independently by extending the resolution of a 6 A x -ray structure (Green, et al., 1979). A 3.0 A model is now available though still in the refinement stages. Not surprisingly it was found that the protein is indeed in the dimeric form and that the arrangement of the dimer is very similar to the one found in BIgY (orthorhombic crystal form)(Papiz, et al., 1986), the other independently determined structure. Changes were observed in the threading of the sequence, in particular between residues 75 and 32 where movements of as much as five residues are found, and in the C- terminus between 141 and 150 where a shift of two residues is observed along a n- strand. These changes result in an overall increase of the hydrophobicity of the pocket. In parallel, cocrystallization of Blg with a variety of ligands has been successful in at least one case where density is evident in the binding cavity.Human apolipoprotein D is present in the fluid of cysts formed during gross- cystic- disease, which is the most common breast disease in premenopausal women, and is a potential biological marker for breast cancer. The protein is found as well, associated with the lipoproteic system in the blood and is produced in high amounts in regenerating rat peripherial nerves. Several structural aspects of the protein from breast cysts were investigated; four of the cysteines were shown to be forming disulphide bridges and the fifth is not present as a free -cysteine. The influence of the pH on the conformational transitions (investigated by CD) and monomer -multimer balance (investigated by gel filtration) shows occurring parallelism with changes on Blg and in particular the transition seen between pH 6.5 and 5.5 could be due to the onset of the dissociation of the tetramer that populates the higher pHs. From the CD studies a 15% a -helix content was determined, more than the 7 -10% found for Blg or the 7% for Rbp but very close to the content on insectocyanin, with which shares 30 -40% residue identity. We examined too, the association of this globular protein with lipid vesicles, and electron- micrographs showed the formation of rouleaux structures, an effect commonly observed with other apolipoproteins; CD showed a small change in the amount of a -helix of the bound -protein .The binding of several hydrophobic molecules was monitored by fluorescence and it was shown that arachidonic acid, a fatty acid with intense biological activity, binds with a association constant of 4.1x107M -1. This ligand provides a possible link between the diverse biological situations where apo D is present. A synthetic antagonist to the thromboxane A2 receptor was shown to bind too but with slightly less affinity

c-di-AMP, a likely master regulator of bacterial K + homeostasis machinery, activates a K + exporter

bis-(3',5')-cyclic diadenosine monophosphate (c-di-AMP) is a second messenger with roles in virulence, cell wall and biofilm formation, and surveillance of DNA integrity in many bacterial species, including pathogens. Strikingly, it has also been proposed to coordinate the activity of the components of K+ homeostasis machinery, inhibiting K+ import, and activating K+ export. However, there is a lack of quantitative evidence supporting the direct functional impact of c-di-AMP on K+ transporters. To gain a detailed understanding of the role of c-di-AMP on the activity of a component of the K+ homeostasis machinery in B. subtilis, we have characterized the impact of c-di-AMP on the functional, biochemical, and physiological properties of KhtTU, a K+/H+ antiporter composed of the membrane protein KhtU and the cytosolic protein KhtT. We have confirmed c-di-AMP binding to KhtT and determined the crystal structure of this complex. We have characterized in vitro the functional properties of KhtTU and KhtU alone and quantified the impact of c-di-AMP and of pH on their activity, demonstrating that c-di-AMP activates KhtTU and that pH increases its sensitivity to this nucleotide. Based on our functional and structural data, we were able to propose a mechanism for the activation of KhtTU by c-di-AMP. In addition, we have analyzed the impact of KhtTU in its native bacterium, providing a physiological context for the regulatory function of c-di-AMP and pH. Overall, we provide unique information that supports the proposal that c-di-AMP is a master regulator of K+ homeostasis machinery.We acknowledge the SOLEIL and ALBA synchrotrons for access and thank their staff for help with data collection. Support of the Biochemical and Biophysical Technologies, Cell Culture and Genotyping and X-ray Crystallography scientific platforms of i3S (Porto, Portugal) is also acknowledged. Mass spectrometry analysis was performed by Hugo Osório at the i3S Proteomics Scientific Platform. This work had support from the Portuguese Mass Spectrometry Network, integrated in the National Roadmap of Research Infrastructures of Strategic Relevance (ROTEIRO/0028/2013; LISBOA-01-0145-FEDER-022125). Work was supported by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020-Operational Programme for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the projects POCI-01–0145-FEDER-029863(PTDC/BIABQM/29863/2017) and by Fundação Luso-Americana para o Desenvolvimento through the FLAD Life Science 2020 award ‘Bacterial K+ transporters are potential antimicrobial targets: mechanisms of transport and regulation’

Enhancing tourism through viticulture enterprises in Douro Region: The Inov@Douro model

This paper describes a business and technological model proposal, known as Inov@Douro, intended to support and to promote competitive and sustained precision agriculture practices in the Portuguese Douro Region. Our approach is based on a distributed cooperative network, tailored to meet the specific needs of viticulture enterprises which also explore tourism as a valuable national and international business source. We present the Inov@Douro model from the knowledge generation point-of-view, intended to support the multidisciplinary concept of a cooperation approach among regional partners. This model aims to represent a new working style for this unique region. As a guideline to attain the implementation of such a model, information technology and infrastructures tools are discussed in order to promote precision agriculture practices while giving valuable and dynamic tourist information to the general public

Characterization of the molecular properties of KtrC, a second RCK domain that regulates a Ktr channel in Bacillus subtilis

RCK (regulating conductance of K+) domains are common regulatory domains that control the activity of eukaryotic and prokaryotic K+ channels and transporters. In bacteria these domains play roles in osmoregulation, regulation of turgor and membrane potential and in pH homeostasis. Whole-genome sequencing unveiled RCK gene redundancy, however the biological role of this redundancy is not well understood. In Bacillus subtilis, there are two closely related RCK domain proteins (KtrA and KtrC) that regulate the activity of the Ktr cation channels. KtrA has been well characterized but little is known about KtrC. We have characterized the structural and biochemical proprieties of KtrC and conclude that KtrC binds ATP and ADP, just like KtrA. However, in solution KtrC exist in a dynamic equilibrium between octamers and non-octameric species that is dependent on the bound ligand, with ATP destabilizing the octameric ring relative to ADP. Accordingly, KtrC-ADP crystal structures reveal closed octameric rings similar to those in KtrA, while KtrC-ATP adopts an open assembly with RCK domains forming a super-helix. In addition, both KtrC-ATP and -ADP octamers are stabilized by the signaling molecule cyclic-di-AMP, which binds to KtrC with high affinity. In contrast, c-di-AMP binds with 100-fold lower affinity to KtrA. Despite these differences we show with an E. coli complementation assay that KtrC and KtrA are interchangeable and able to form functional transporters with both KtrB and KtrD. The distinctive properties of KtrC, in particular ligand-dependent assembly/disassembly, suggest that this protein has a specific physiological role that is distinct from KtrA.Work was supported by Fundação Luso-Americana para o Desenvolvimento through the FLAD Life Science 2020 award entitled “Bacterial K+ transporters are potential antimicrobial targets: mechanisms of transport and regulation” and by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-029863 (PTDC/BIA-BQM/29863/2017) and of project "Institute for Research and Innovation in Health Sciences" (POCI-01-0145-FEDER-007274). RR was supported by FCT fellowship (SFRH/BPD/111525/2015), CMT-D was supported by FCT fellowship (SFRH/BD/123761/2016 ).

O baixista moderno: questões de versatilidade na performance

Mestrado em MúsicaNo âmbito da performance musical, mais precisamente no jazz, podemos encontrar indivíduos que frequentemente apresentam destrezas performativas em diferentes instrumentos. Esta pesquisa, no quadro da etnomusicologia e dos estudos de jazz, propõe uma análise a partir da relação entre as variáveis instrumentos e instrumentista, pontuada nos casos dos baixistas eléctricos e baixistas de jazz. O problema central em análise prende-se com a versatilidade do baixista quando circula entre tipologias de instrumentos diferentes. A partir das entrevistas realizadas e da observação participante, optou-se por desenvolver uma análise de conteúdo, com foco em temas que constituem a abordagem principal do trabalho: “o intercâmbio idiomático”. Os elementos em análise são: músico performer, instrumento, estética e mercado. A metodologia assenta na análise destes quatros elementos e no uso retrospectivo da bricolagem.In the context of musical performance, more precisely in jazz, we can find individuals who often present performative skills in different instruments. This research, in the context of ethnomusicology and jazz studies, proposes an analysis based on the relationship between instrumental and instrumentalist variables, punctuated in the cases of jazz electric basses and double basses. The central problem in analysis concerns the versatility of the bass player when he circulates between different types of instruments. Based on interviews and participant observation, it was decided to develop a content analysis, focusing on themes that constitute the main approach of the work: “idiomatic interchange”. The elements under analysis are: musician performer, instrument, aesthetics and market. The methodology is based on the analysis of these four elements and the retrospective use of bricolage