Interações medicamentosas em doentes crónicos, diabéticos e com dislipidémia [artigo]

O aumento de fármacos disponíveis aumenta a probabilidade de ocorrência de interações medicamentosas, já que a administração simultânea de dois ou mais medicamentos a um mesmo paciente se tornou uma prática comum1. A incidência desde fenómeno tende a aumentar proporcionalmente em relação ao número de fármacos prescritos2. A maioria dos estudos efetuados sobre IMs decorreu em ambiente hospitalar, havendo até à data pouca investigação no contexto da comunidade. Este estudo procurou uma imagem da realidade em termos de IMs potenciais num segmento específico da população, doentes com dislipidémia e/ou diabetes, em contexto comunitário realizando um estudo observacional transversal3, com recurso a 101 prescrições de utentes de farmácias do distrito do Porto. As prescrições de interesse foram analisadas recorrendo à base de dados Micromedex Healthcare Systems®.info:eu-repo/semantics/publishedVersio

Capacitated Center Problems with Two-Sided Bounds and Outliers

In recent years, the capacitated center problems have attracted a lot of research interest. Given a set of vertices $V$, we want to find a subset of vertices $S$, called centers, such that the maximum cluster radius is minimized. Moreover, each center in $S$ should satisfy some capacity constraint, which could be an upper or lower bound on the number of vertices it can serve. Capacitated $k$-center problems with one-sided bounds (upper or lower) have been well studied in previous work, and a constant factor approximation was obtained. We are the first to study the capacitated center problem with both capacity lower and upper bounds (with or without outliers). We assume each vertex has a uniform lower bound and a non-uniform upper bound. For the case of opening exactly $k$ centers, we note that a generalization of a recent LP approach can achieve constant factor approximation algorithms for our problems. Our main contribution is a simple combinatorial algorithm for the case where there is no cardinality constraint on the number of open centers. Our combinatorial algorithm is simpler and achieves better constant approximation factor compared to the LP approach

Laparoendoscopic single-site (LESS) sacrocolpopexy: feasibility and efficacy of knotless procedure performed with conventional instruments

The aim of this paper was to report a case of a patient with stage IV vaginal vault prolapse treated by laparoendoscopic single-site (LESS) sacrocolpopexy using an Alexis retractor and a surgical glove attached to three trocars through a 3.5-cm umbilical incision. Only conventional laparoscopic instruments were used for intrabdominal dissection of vagina and peritoneum. The mesh was fixed to the vaginal fornix and to the sacral periosteum from the promontory using running sutures hold in the extremities by polymer clips. The posterior peritoneum was closed over the mesh. LESS sacrocolpopexy performed with conventional instruments is a difficult but feasible and efficient technique to treat vaginal vault prolapse that respects the principles of conventional laparoscopic or open repairs. Alexis retractor associated with knotless sutures are technical options that simplify LESS reconstructive surgical maneuvers

A mechanism for the inhibition of DNA-PK-mediated DNA sensing by a virus

The innate immune system is critical in the response to infection by pathogens and it is activated by pattern recognition receptors (PRRs) binding to pathogen associated molecular patterns (PAMPs). During viral infection, the direct recognition of the viral nucleic acids, such as the genomes of DNA viruses, is very important for activation of innate immunity. Recently, DNA-dependent protein kinase (DNA-PK), a heterotrimeric complex consisting of the Ku70/Ku80 heterodimer and the catalytic subunit DNA-PKcs was identified as a cytoplasmic PRR for DNA that is important for the innate immune response to intracellular DNA and DNA virus infection. Here we show that vaccinia virus (VACV) has evolved to inhibit this function of DNA-PK by expression of a highly conserved protein called C16, which was known to contribute to virulence but by an unknown mechanism. Data presented show that C16 binds directly to the Ku heterodimer and thereby inhibits the innate immune response to DNA in fibroblasts, characterised by the decreased production of cytokines and chemokines. Mechanistically, C16 acts by blocking DNA-PK binding to DNA, which correlates with reduced DNA-PK-dependent DNA sensing. The C-terminal region of C16 is sufficient for binding Ku and this activity is conserved in the variola virus (VARV) orthologue of C16. In contrast, deletion of 5 amino acids in this domain is enough to knockout this function from the attenuated vaccine strain modified vaccinia virus Ankara (MVA). In vivo a VACV mutant lacking C16 induced higher levels of cytokines and chemokines early after infection compared to control viruses, confirming the role of this virulence factor in attenuating the innate immune response. Overall this study describes the inhibition of DNA-PK-dependent DNA sensing by a poxvirus protein, adding to the evidence that DNA-PK is a critical component of innate immunity to DNA viruses

IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection

Funding: This work was funded by a Career Development Fellowship (1028634) and a project grant (GRNT1028641) awarded to AHa by the Australian National Health & Medical Research Council (NHMRC). IS was supported by The University of Queensland Centennial and IPRS Scholarships. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Magnetism and its microscopic origin in iron-based high-temperature superconductors

High-temperature superconductivity in the iron-based materials emerges from, or sometimes coexists with, their metallic or insulating parent compound states. This is surprising since these undoped states display dramatically different antiferromagnetic (AF) spin arrangements and N$\rm \acute{e}$el temperatures. Although there is general consensus that magnetic interactions are important for superconductivity, much is still unknown concerning the microscopic origin of the magnetic states. In this review, progress in this area is summarized, focusing on recent experimental and theoretical results and discussing their microscopic implications. It is concluded that the parent compounds are in a state that is more complex than implied by a simple Fermi surface nesting scenario, and a dual description including both itinerant and localized degrees of freedom is needed to properly describe these fascinating materials.Comment: 14 pages, 4 figures, Review article, accepted for publication in Nature Physic