Dendrimer synthesis should not be tedious and time-consuming. By utilizing an AB 2 -CD 2 approach and having orthogonal, "clickable" groups on each monomer, the time for dendrimer assembly can be drastically reduced. This was shown by preparation of a sixth generation dendrimer from starting monomer units in a single day.

By taking advantage of the orthogonal nature of thiol-ene coupling and anhydride based esterification reactions, a facile and chemoselective strategy to dendritic macromolecules has been developed. The ability to interchange growth steps based on thiol-ene and anhydride chemistry allows the synthesis of fifth-generation dendrimers in only five steps and under benign reaction conditions. In addition, the presented coupling chemistries eliminate the traditional need for protection/deprotection steps and afford dendrimers in high yield and purity. The modularity of this strategy coupled with the latent reactivity of the alkene/hydroxyl chain ends was demonstrated by using different cores (alkene and hydroxyl functional), various AB 2 and CD 2 monomers and a range of chain end groups. As a result, three dendritic libraries were prepared which exhibited tunability of both the chemical functionality and physical properties including the fabrication of PEG hydrogels.

Well-defined dendronized cellulose substrates displaying multiple representations of dual-functionality were constructed by taking advantage of the efficiency of the click reaction combined with traditional anhydride chemistry. First, activated cellulose surfaces were decorated with several generations of dendrons, and their peripheral reactive groups were subsequently reacted with a trifunctional orthogonal monomer. The generated substrate tool box was successfully explored by accurately tuning the surface function using a versatile orthogonal dual postfunctionalization approach. In general, the reactions were monitored by using a click-dye reagent or a quartz crystal microbalance (QCM) technique, and the resulting surfaces were well-characterized using XPS, FT-IR, and contact angle measurements. Utilizing this approach two different surfaces have been obtained; that is, triethylenglycol oligomers and amoxicillin molecules were efficiently introduced to the dendritic surface. As a second example, mannose-decorated hydroxyl functional surfaces illustrated their potential as biosensors by multivalent detection of lectin protein at concentration as low as 5 nM.

Redox-sensitive hyperbranched dendritic-linear polymers (HBDLPs) were prepared and stabilized individually as unimolecular micelles with diameters in the range 25-40 nm. The high molecular weight (500-950 kDa), core-shell amphiphilic structures were synthesized through a combination of self-condensing vinyl copolymerization (SCVCP) and atom transfer radical polymerization (ATRP). Cleavable disulfide bonds were introduced, either in the backbone, or in pendant groups, of the hyperbranched core of the HBDLPs. By triggered reductive degradation, the HBDLPs showed up to a 7-fold decrease in molecular weight, and the extent of degradation was tuned by the amount of incorporated disulfides. The HBDLP with pendant disulfide-linked functionalities in the hyperbranched core was readily postfunctionalized with a hydrophobic dye, as a mimic for a drug. An instant release of the dye was observed as a response to a reductive environment similar to the one present intracellularly. The proposed strategy shows a facile route to highly stable unimolecular micelles, which attractively exhibit redox-responsive degradation and cargo release properties.

Drug hypersensitivity reactions result from the activation of the immune system by drugs or their metabolites. The clinical presentations of drug hypersensitivity can range from relatively mild local manifestations to severe systemic syndromes that can be life-threatening. As in other allergic reactions, the causes are multifactorial as genetic, metabolic and concomitant factors may influence the occurrence of drug hypersensitivity. Formation of drug protein adducts is considered a key step in drug adverse reactions, and in particular in the immunological recognition in drug hypersensitivity reactions. Nevertheless, non-covalent interactions of drugs with receptors in immune cells or with MHC clefts and/or exposed peptides can also play an important role. In recent years, development of proteomic approaches has allowed the identification and characterization of the protein targets for modification by drugs in vivo and in vitro, the nature of peptides exposed on MHC molecules, the changes in protein levels induced by drug treatment, and the concomitant modifications induced by danger signals, thus providing insight into context factors. Nevertheless, given the complexity and multifactorial nature of drug hypersensitivity reactions, understanding the underlying mechanisms also requires the integration of knowledge from genomic, metabolomic and clinical studies.

The diagnosis of drug hypersensitivity reactions (DHR) is complex, with many potential pitfalls. Although the use of clinical history and skin testing can be valuable, drug provocation testing (DPT) remains the gold standard for many DHR. However, DPT carries some potential risk and should not be performed for severe reactions. There is therefore a general consensus on the need to improve in vitro tests to achieve safe and accurate diagnosis of DHR. A range of in vitro approaches can be applied depending on the type of reaction and the immunological mechanism involved, i.e. IgE- or T-cell-mediated. However, commercially available tests only exist for a handful of drugs, and only for drugs that provoke IgEmediated DHR. Of the cellular tests that focus on the identification of the culprit drug, the best validated is the basophil activation test used for evaluating IgE-mediated reactions. For T-cell-mediated DHR, the lymphocyte transformation test and enzyme-linked immunosorbent spot appear to be the most promising. However, these tests often show low sensitivity. Despite their current drawbacks, in vitro tests can complement in vivo testing and further work in this area will be crucial to improve our current arsenal of tools for the detection and assessment of DHR. For this, the use of appropriate and relevant drug metabolites as well as other factors that can amplify the cell response as well as the use of multiple tests in concert key to improving in vitro diagnosis. Such improvements will be crucial to diagnose patients with severe reactions for whom DPT cannot be performed.

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The economic crisis has entailed a general increase in job demands and reduction in compensating factors, modifying the fairness of the employment relationship. In this longitudinal study, we analyze the effects of the moderating role of organizational justice on the job characteristics-job satisfaction relationship. A total of 593 employees working for 42 Spanish companies answered the questionnaires at two points in time. Results showed that the job and the social characteristics, as well as distributive justice, in time 1 predict job satisfaction in time 2. Additionally, interactional justice moderated the relationship between job characteristics and job satisfaction. In conclusion, work design, as well as fair interactions at work, may increase job satisfaction. Desenho do trabalho e satisfação: o papel moderador da justiça organizacional Resumo A crise econômica implicou em um aumento geral nas demandas de emprego e redução nas compensações, modificando a equidade nas relações de trabalho. Neste estudo longitudinal, analisamos os efeitos moderadores da justiça organizacional entre as características do trabalho e a satisfação laboral. Um total de 593 trabalhadores de 42 empresas espanholas responderam aos questionários em dois momentos temporais. Os resultados mostraram que as características da tarefa e as sociais assim como a justiça distributiva em tempo 1 prediz a satisfação laboral em tempo 2. Além disso, encontrou-se um efeito de interação entre as características da tarefa e a justiça interacional sobre a satisfação laboral. Conclui-se que além do desenho do trabalho é importante levar em consideração que interações justas no trabalho podem incrementar a satisfação laboral. Diseño del trabajo y satisfacción: el rol modulador de la justicia organizacional Resumen La crisis económica ha implicado un aumento general de las demandas laborales y una reducción de las compensaciones, modificando la equidad en las relaciones laborales. En este estudio longitudinal, analizamos los efectos moduladores de la justicia organizacional entre las características del trabajo y la satisfacción laboral. 593 empleados de 42 empresas españolas contestaron el cuestionario en dos momentos temporales distintos. Los resultados mostraron que las características de la tarea y las sociales, así como la justicia distributiva en tiempo 1 predicen la satisfacción laboral en tiempo 2. Además, se encontró un efecto de interacción entre las características de tarea y la justicia interaccional sobre la satisfacción laboral. En conclusión, además del diseño del puesto es importante tener en cuenta que interacciones justas en el trabajo pueden incrementar la satisfacción laboral.