pH-responsive self-assembly of amyloid fibrils for dual hydrolase-oxidase reactions

Altres ajuts: ICREA Academia 2015There is an increasing interest in synthetic systems that can execute bioinspired chemical reactions without requiring the complex structures that characterize enzymes in their components. The hierarchical self-assembly of peptides provides a means to create catalytic microenvironments. Ideally, as it occurs in enzymes, the catalytic activity of peptide nanostructures should be reversibly regulated. In a typical enzyme mimetic design, the peptide's self-assembling and catalytic activities are segregated into different regions of the sequence. Here, we aimed to design minimal peptides in which the self-assembly and function were all encoded in the same amino acids. Moreover, we wanted to endow the resulting one-component nanomaterial with divergent, chemically unrelated, catalytic activities, a property not observed in natural enzymes. We show that short peptides consisting only of histidine and tyrosine residues, arranged in a binary pattern, form biocompatible amyloid-like fibrils and hydrogels combining hydrolytic and electrocatalytic activities. The nanofibers' mesoscopic properties are controlled by pH, the transition between assembled active β-sheet fibrils, and disassembled inactive random coil species occurring in a physiologically relevant pH range. The structure of one of such amyloid-like fibrils, as derived from molecular dynamic simulations, provides insights on how they attain this combination of structural and catalytic properties

Drug-Related Problems in Elderly Patients Attended to by Emergency Services

The progressive aging and comorbidities of the population have led to an increase in the number of patients with polypharmacy attended to in the emergency department. Drug-related problems (DRPs) have become a major cause of admission to these units, as well as a high rate of short-term readmissions. Anticoagulants, antibiotics, antidiabetics, and opioids have been shown to be the most common drugs involved in this issue. Inappropriate polypharmacy has been pointed out as one of the major causes of these emergency visits. Different ways of conducting chronic medication reviews at discharge, primary care coordination, and phone contact with patients at discharge have been shown to reduce new hospitalizations and new emergency room visits due to DRPs, and they are key elements for improving the quality of care provided by emergency services