Personalized nanomedicine: a revolution at the nanoscale

Nanomedicine is an interdisciplinary research field that results from the application of nanotechnology to medicine and has the potential to significantly improve some current treatments. Specifically, in the field of personalized medicine, it is expected to have a great impact in the near future due to its multiple advantages, namely its versatility to adapt a drug to a cohort of patients. In the present review, the properties and requirements of pharmaceutical dosage forms at the nanoscale, so-called nanomedicines, are been highlighted. An overview of the main current nanomedicines in pre-clinical and clinical development is presented, detailing the challenges to the personalization of these therapies. Next, the process of development of novel nanomedicines is described, from their design in research labs to their arrival on the market, including considerations for the design of nanomedicines adapted to the requirements of the market to achieve safe, effective, and quality products. Finally, attention is given to the point of view of the pharmaceutical industry, including regulation issues applied to the specific case of personalized medicine. The authors expect this review to be a useful overview of the current state of the art of nanomedicine research and industrial production, and the future opportunities of personalized medicine in the upcoming years. The authors encourage the development and marketing of novel personalized nanomedicines

Planeamiento Estratégico Situacional: Su Evolución En El Departamento De Ingeniería Química

El Departamento de Ingeniería Química de la UTN - FRBA viene desarrollando un proceso de autoevaluación y mejoras implementadas sobre la formación del ingeniero químico desde el año 1990. El objetivo del presente trabajo es describir y analizar, bajo la lupa del planeamiento estratégico situacional, la gestión académica que se viene desarrollando en el mismo, desde 1990 a la fecha, teniendo en cuenta las distintas etapas por las que fue transitando: cambios curriculares, proceso de autoevaluación universitaria, proceso de acreditación de la carrera, en las que se produjeron cambios periódicos en los grupos de gestión y organismos de gobierno: Secretarios, Consejos Departamentales y Académicos, Directores de Departamento, como así también de recambio generacional

Rift Valley fever virus structural proteins: expression, characterization and assembly of recombinant proteins

BACKGROUND: Studies on Rift Valley Fever Virus (RVFV) infection process and morphogenesis have been hampered due to the biosafety conditions required to handle this virus, making alternative systems such as recombinant virus-like particles, that may facilitate understanding of these processes are highly desirable. In this report we present the expression and characterization of RVFV structural proteins N, Gn and Gc and demonstrate the efficient generation of RVFV virus-like particles (VLPs) using a baculovirus expression system. RESULTS: A recombinant baculovirus, expressing nucleocapsid (N) protein of RVFV at high level under the control of the polyhedrin promoter was generated. Gel filtration analysis indicated that expressed N protein could form complex multimers. Further, N protein complex when visualized by electron microscopy (EM) exhibited particulate, nucleocapsid like-particles (NLPs). Subsequently, a single recombinant virus was generated that expressed the RVFV glycoproteins (Gn/Gc) together with the N protein using a dual baculovirus vector. Both the Gn and Gc glycoproteins were detected not only in the cytoplasm but also on the cell surface of infected cells. Moreover, expression of the Gn/Gc in insect cells was able to induce cell-cell fusion after a low pH shift indicating the retention of their functional characteristics. In addition, assembly of these three structural proteins into VLPs was identified by purification of cells' supernatant through potassium tartrate-glycerol gradient centrifugation followed by EM analysis. The purified particles exhibited enveloped structures that were similar to the structures of the wild-type RVFV virion particle. In parallel, a second recombinant virus was constructed that expressed only Gc protein together with N protein. This dual recombinant virus also generated VLPs with clear spiky structures, but appeared to be more pleomorphic than the VLPs with both glycoproteins, suggesting that Gc and probably also Gn interacts with N protein complex independent of each other. CONCLUSION: Our results suggest that baculovirus expression system has enormous potential to produce large amount of VLPs that may be used both for fundamental and applied research of RVFV

Recovery of African horse sickness virus from synthetic RNA.

African horse sickness virus (AHSV) is an insect-vectored emerging pathogen of equine species. AHSV (nine serotypes) is a member of the genus Orbivirus, with a morphology and coding strategy similar to that of the type member, bluetongue virus. However, these viruses are distinct at the genetic level, in the proteins they encode and in their pathobiology. AHSV infection of horses is highly virulent with a mortality rate of up to 90 %. AHSV is transmitted by Culicoides, a common European insect, and has the potential to emerge in Europe from endemic countries of Africa. As a result, a safe and effective vaccine is sought urgently. As part of a programme to generate a designed highly attenuated vaccine, we report here the recovery of AHSV from a complete set of RNA transcripts synthesized in vitro from cDNA clones. We have demonstrated the generation of mutant and reassortant AHSV genomes, their recovery, stable passage, and characterization. Our findings provide a new approach to investigate AHSV replication, to design AHSV vaccines and to aid diagnosis

A dinamização do sistema de vigilância alimentar e nutricional em Campo Magro

Orientador: Suely Teresinha SchmidtMonografia (especialização) - Universidade Federal do Paraná, Especialização em Gestão Pública em SaúdeInclui referênciasNão inclui resum

Structural constraints in the packaging of bluetongue virus genomic segments.

The mechanism used by bluetongue virus (BTV) to ensure the sorting and packaging of its 10 genomic segments is still poorly understood. In this study, we investigated the packaging constraints for two BTV genomic segments from two different serotypes. Segment 4 (S4) of BTV serotype 9 was mutated sequentially and packaging of mutant ssRNAs was investigated by two newly developed RNA packaging assay systems, one in vivo and the other in vitro. Modelling of the mutated ssRNA followed by biochemical data analysis suggested that a conformational motif formed by interaction of the 5' and 3' ends of the molecule was necessary and sufficient for packaging. A similar structural signal was also identified in S8 of BTV serotype 1. Furthermore, the same conformational analysis of secondary structures for positive-sense ssRNAs was used to generate a chimeric segment that maintained the putative packaging motif but contained unrelated internal sequences. This chimeric segment was packaged successfully, confirming that the motif identified directs the correct packaging of the segment

Rotavirus Genomic RNA Complex Forms via Specific RNA-RNA Interactions: Disruption of RNA Complex Inhibits Virus Infectivity.

Rotavirus (RV), a member of the Reoviridae family, causes infection in children and infants, with high morbidity and mortality. To be viable, the virus particle must package a set of eleven RNA segments. In order to understand the packaging mechanism, here, we co-synthesized sets of RNA segments in vitro in different combinations and detected by two alternate methods: the electrophoretic mobility shift assay (EMSA) and the RNA-bead pull-down assay. We showed that viral positive-sense RNA segments interact with each other in a specific manner, forming RNA complexes, and that the RNA-RNA interactions followed a sequential order initiated by small RV segments. Further, we demonstrated that RNA complexes were perturbed by targeted specific antisense oligoribonucleotides (ORNs) complementary to short RNA sequences, indicating that the RNA-RNA interactions between different segments were sequence-specific. The same inhibitory ORNs also had the capability to inhibit virus replication. The combined in vitro and in vivo data inferred that RNA-RNA interactions and specific complex formation are essential for sorting different segments, possibly prior to, or during, genome packaging. As genome assembly is a universal requirement in the Reoviridae family, this work offers an approach towards a further understanding of the sorting and packaging mechanisms of RV and related dsRNA (double-stranded RNA) viruses

Atomic model of a nonenveloped virus reveals pH sensors for a coordinated process of cell entry.

Viruses sense environmental cues such as pH to engage in membrane interactions for cell entry during infection, but how nonenveloped viruses sense pH is largely undefined. Here, we report both high- and low-pH structures of bluetongue virus (BTV), which enters cells via a two-stage endosomal process. The receptor-binding protein VP2 possesses a zinc finger that may function to maintain VP2 in a metastable state and a conserved His866, which senses early-endosomal pH. The membrane-penetration protein VP5 has three domains: dagger, unfurling and anchoring. Notably, the β-meander motif of the anchoring domain contains a histidine cluster that can sense late-endosomal pH and also possesses four putative membrane-interaction elements. Exposing BTV to low pH detaches VP2 and dramatically refolds the dagger and unfurling domains of VP5. Our biochemical and structure-guided-mutagenesis studies support these coordinated pH-sensing mechanisms

Comunicando en silencio. Estudio sobre la relación entre la comunicación no verbal y el proceso de enseñanza-aprendizaje en la etapa de educación infantil en Perú

La comunicación no verbal es un aspecto que interviene en el proceso de enseñanza-aprendizaje. Resulta positivo que el maestro de Educación Infantil conozca y valore este tipo de comunicación, haciendo uso de los elementos que ésta conlleva. De esta manera, el maestro puede llegar a conseguir una mejor relación con sus alumnos, dando a estos la seguridad y confianza que necesitan, además de mejorar la comunicación en el aula, favoreciendo así el proceso de enseñanza-aprendizaje. Para ello, también resultaría necesario conocer la cultura en la que nos encontramos y, por lo tanto, el uso y la importancia de los distintos elementos comunicativos no verbales según sus hábitos, costumbres y creencias. El contexto de dos centros peruanos nos ofrece conocer, a partir de un humilde estudio, el importante papel que toman los elementos cinésicos en el proceso de enseñanza-aprendizaje de esta etapa

Pra lá e pra cá, vou a qualquer lugar! o papel do corpo e do seu movimento no contexto das tarefas para o desenvolvimento da percepção espacial na Educação Infantil

Neste artigo relatamos um estudo cujo propósito foi analisar como ocorre o desenvolvimento de noções de localização e orientação no espaço pela criança da Educação Infantil e como esse processo pode ser favorecido e impulsionado por tarefas matemáticas que tenham o corpo e o seu movimento como elementos centrais. O estudo realizado foi de abordagem qualitativa, uma pesquisa de intervenção com crianças da Creche UFBA, cujos dados foram gerados por meio da implementação de sequências de tarefas baseadas em critérios de idoneidade didática. Os resultados revelaram que, por meio da vivência corporal e da exploração do espaço em torno de seu próprio corpo e dos objetos, as crianças se aproximaram de noções relativas à localização e orientação (sentido e direção) enriquecendo e ampliando a sua percepção de espaço