Schizophrenia is a chronic mental disorder characterized by distortion of thinking, language, emotion, perception, and self-behavior (1,2). It is generally believed that schizophrenia is related to genetic, environmental, psychosocial factors and social defeat (2,3). In current years, the study found that there was a significant difference in brain immune cell density of patients with schizophrenia compared with healthy people (4), and then the mild encephalitis hypothesis of schizophrenia was put forward (5). The limbic system contains several structures of the brain involving connectivity, architecture, function, and development, including the hippocampus, amygdala, parahippocampal
Background
Drug-drug interactions (DDIs) are factors of adverse drug reactions and are more common in elderly patients. Identifying potential DDIs can prevent the related risks. Fewer studies of potential DDIs in prescribing for elderly patients in outpatient clinics. This study aimed to investigate the prevalence and associated factors with potential DDIs and potentially clinically significant DDIs (csDDIs) among elderly outpatients based on 3 DDIs databases.
Methods
A cross-sectional study was carried out on outpatients (≥65 years old) of a tertiary care hospital in China between January and March 2022. Patients’ prescriptions, including at least 1 systemic drug, were consecutively collected. The potential DDIs were identified by Lexicomp
®
, Micromedex
®
, and DDInter. Patient-related clinical parameter recorded at the prescriptions and DDIs with higher risk rating was analyzed. Variables showing association in univariate analysis (P<0.2) were included in logistic regression analysis. Weighted kappa analysis was used to analyze the consistencies of different databases.
Results
A total of 19,991 elderly outpatients were involved in the study, among whom 21,527 drug combinations including 486 drugs occurred. Lexicomp
®
, Micromedex
®
, and DDInter respectively identified 32.22%, 32.93%, and 22.62% of patients have at least one potential DDIs, meanwhile, 9.16%, 14.53%, and 4.56% of patients have at least one potential csDDIs. Under any evaluation criteria, polypharmacy and neurology visits were risk factors for csDDIs. Lexicomp
®
has the highest coverage rate (87.86%) for drugs. Micromedex
®
identified the most csDDIs (740 drug combinations). Drugs used in diabetes and psycholeptics were frequently found in the csDDIs of 2 commercial databases. The consistency between Lexicomp
®
and Micromedex
®
was moderate (weighted kappa 0.473). DDInter had fair consistencies with the other databases.
Conclusions
This study showed the prevalence of potential DDIs is high in elderly outpatients and potential csDDIs were prevalent. Considering the relative risk, pre-warning of potential DDIs before outpatient prescribing is necessary. As the consistencies among identification criteria are not good, more research is needed to focus on actual adverse outcomes to promote accurate prevention of csDDIs.
Ubiquitin (Ub)-like protein ISG15 (interferon-stimulated gene 15) regulates innate immunity and links with the evasion of host response by viruses such as SARS-CoV-2. Dissecting ISGylation pathways recently received increasing attention which can inform related disease interventions, but such studies necessitate the preparation and development of various ISG15 protein tools. Here, we find that the leader protease (Lb pro ) encoded by foot-and-mouth disease virus can promote ligation reactions between recombinant ISG15 and synthetic glycyl compounds, generating protein tools such as ISG15-propargylamide and ISG15-rhod-amine110, which are needed for cellular proteomic studies of deISGylases, and the screening and evaluation of inhibitors against SARS-CoV-2 papain-like protease (PLpro). Furthermore, this strategy can be also used to load ISG15 onto the lysine of a synthetic peptide through an isopeptide bond, and prepare Ub and NEDD8 (ubiquitin-like protein Nedd8) protein tools.
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