Comparison of health resource usage and costs associated with first-generation and second-generation long-acting injectable antipsychotics for patients with schizophrenia: A nationwide population-based cohort study.

The aim of this study was to examine psychiatric resource utilization, medical costs and clinical outcomes for patients with schizophrenia who received either first-generation or second-generation long-acting injectable (LAI) antipsychotics. A retrospective cohort study was conducted using data from Taiwan's National Health Insurance Research Database (NHIRD). Patients who began either first-generation or second-generation LAI treatment between 2015 and 2017 were enrolled and followed for three years. The data were evaluated using survival analysis and Cox proportional hazards regression models. Our findings demonstrated that both first- and second-generation LAI therapies led to notable reductions in the frequency of psychiatric hospitalizations and the duration of hospital stays when compared to the initial measurements. Additionally, the second-generation LAI group exhibited significantly lower rates of psychiatric emergencies and hospitalizations, as well as shorter hospital stays, compared to the first-generation LAI group. However, it is worth noting that the second-generation LAI group incurred higher pharmacy fees despite these favorable outcomes. The utilization of both first- and second-generation LAIs can enhance medication adherence and decrease the risk of acute exacerbation in patients with schizophrenia. These findings hold significant implications for schizophrenia management and the efficient allocation of healthcare resources.

Advantages of DES over BMS in Preventing the Risk of Myocardial Infarction, Ischemic Stroke, and Mortality in Various Populations.

Backgrounds: Previous studies have demonstrated that drug-eluting stents (DESs) are more effective than bare metal stents (BMSs) in reducing the risk of myocardial infarction in the short term, but the long-term preventive benefits for myocardial infarction, ischemic stroke, and mortality are not clear. Objective: This study deeply analyzed the long-term (within 3 years) advantages of the use of DESs in preventing the risk of myocardial infarction, ischemic stroke, and mortality in various populations compared with those of using BMSs. Methods: This was a retrospective observational cohort study. We used the 2015-2019 claims data from Taiwan's National Health Insurance Research Database. Patients over the age of 18 who underwent coronary stent placement (both DESs and BMSs) for the first time in 2016 were included in the study population. Propensity-score matching was applied to increase the comparability of the DES and BMS groups. We used a Cox proportional hazard regression analysis to compare the effectiveness of DESs and BMSs in preventing myocardial infarction, ischemic stroke, and all-cause mortality. A subgroup analysis was also performed. Results: In total, 21,608 cases were included in this study. Overall, the risk of myocardial infarction (aHR = 0.82; 95% CI: 0.78-0.85), ischemic stroke (aHR = 0.88; 95% CI: 0.81-0.95), and mortality (aHR = 0.61; 95% CI: 0.57-0.65) in the DES group were significantly lower than those in the BMS group. However, in some special cases, the results were not statistically significant. In particular, in patients with obesity (aHR = 2.61; 95% CI: 1.20-5.69), the DES group appeared to have a significantly higher long-term intermediate ischemic risk than the BMS group. Conclusions and Relevance: In conclusion, although DESs were more effective than BMSs in reducing the risk of long-term myocardial infarction, ischemic stroke, and mortality, this study also found that, in some cases, the advantages of DESs over BMSs were not clearly observed.

RINT-1 interacts with MSP58 within nucleoli and plays a role in ribosomal gene transcription.

The nucleolus is the cellular site of ribosomal (r)DNA transcription and ribosome biogenesis. The 58-kDa microspherule protein (MSP58) is a nucleolar protein involved in rDNA transcription and cell proliferation. However, regulation of MSP58-mediated rDNA transcription remains unknown. Using a yeast two-hybrid system with MSP58 as bait, we isolated complementary (c)DNA encoding Rad50-interacting protein 1 (RINT-1), as a MSP58-binding protein. RINT-1 was implicated in the cell cycle checkpoint, membrane trafficking, Golgi apparatus and centrosome dynamic integrity, and telomere length control. Both in vitro and in vivo interaction assays showed that MSP58 directly interacts with RINT-1. Interestingly, microscopic studies revealed the co-localization of MSP58, RINT-1, and the upstream binding factor (UBF), a rRNA transcription factor, in the nucleolus. We showed that ectopic expression of MSP58 or RINT-1 resulted in decreased rRNA expression and rDNA promoter activity, whereas knockdown of MSP58 or RINT-1 by siRNA exerted the opposite effect. Coexpression of MSP58 and RINT-1 robustly decreased rRNA synthesis compared to overexpression of either protein alone, whereas depletion of RINT-1 from MSP58-transfected cells enhanced rRNA synthesis. We also found that MSP58, RINT-1, and the UBF were associated with the rDNA promoter using a chromatin immunoprecipitation assay. Because aberrant ribosome biogenesis contributes to neoplastic transformation, our results revealed a novel protein complex involved in the regulation of rRNA gene expression, suggesting a role for MSP58 and RINT-1 in cancer development.

Identification and characterization of nuclear and nucleolar localization signals in 58-kDa microspherule protein (MSP58).

BACKGROUND: MSP58 is a nucleolar protein associated with rRNA transcription and cell proliferation. Its mechanism of translocation into the nucleus or the nucleolus, however, is not entirely known. In order to address this lack, the present study aims to determine a crucial part of this mechanism: the nuclear localization signal (NLS) and the nucleolar localization signal (NoLS) associated with the MSP58 protein. RESULTS: We have identified and characterized two NLSs in MSP58. The first is located between residues 32 and 56 (NLS1) and constitutes three clusters of basic amino acids (KRASSQALGTIPKRRSSSRFIKRKK); the second is situated between residues 113 and 123 (NLS2) and harbors a monopartite signal (PGLTKRVKKSK). Both NLS1 and NLS2 are highly conserved among different vertebrate species. Notably, one bipartite motif within the NLS1 (residues 44-56) appears to be absolutely necessary for MSP58 nucleolar localization. By yeast two-hybrid, pull-down, and coimmunoprecipitation analysis, we show that MSP58 binds to importin α1 and α6, suggesting that nuclear targeting of MSP58 utilizes a receptor-mediated and energy-dependent import mechanism. Functionally, our data show that both nuclear and nucleolar localization of MSP58 are crucial for transcriptional regulation on p21 and ribosomal RNA genes, and context-dependent effects on cell proliferation. CONCLUSIONS: Results suggest that MSP58 subnuclear localization is regulated by two nuclear import signals, and that proper subcellular localization of MSP58 is critical for its role in transcriptional regulation. Our study reveals a molecular mechanism that controls nuclear and nucleolar localization of MSP58, a finding that might help future researchers understand the MSP58 biological signaling pathway.