Active monitoring of antifungal adverse events in hospitalized patients based on Global Trigger Tool method

BackgroundThe increasing prevalence of fungal infections necessitates broader use of antifungal medications. However, the prevalence of adverse drug events (ADEs) restricts their clinical application. This study aimed to develop a reliable ADEs trigger for antifungals to enable proactive ADEs monitoring, serving as a reference for ADEs prevention and control.MethodsThis investigation comprises two phases. Initially, the trigger was established via a literature review, extraction of relevant items, and refinement through Delphi expert consultation. Subsequently, the validity of the trigger was assessed by analyzing hospital records of antifungal drug users from 1 January 2019 to 31 December 2020. The correlation between each trigger signal and ADEs occurrence was examined, and the sensitivity and specificity of the trigger were evaluated through the spontaneous reporting system (SRS) and Global Trigger Tool (GTT). Additionally, risk factors contributing to adverse drug events (ADEs) resulting from antifungal use were analyzed. Results: Twenty-one preliminary triggers were refined into 21 final triggers after one expert round. In the retrospective analysis, the positive trigger rate was 65.83%, with a positive predictive value (PPV) of 28.75%. The incidence of ADEs in inpatients was 28.75%, equating to 44.58 ADEs per 100 admissions and 33.04 ADEs per 1,000 patient days. Predominant ADEs categories included metabolic disturbances, gastrointestinal damage, and skin rashes. ADEs severity was classified into 36 cases at grade 1, 160 at grade 2, and 18 at grade 3. The likelihood of ADEs increased with longer stays, more positive triggers, and greater comorbidity counts.ConclusionThis study underscores the effectiveness of the GTT in enhancing ADEs detection during antifungal medication use, thereby confirming its value as a monitoring tool

The coordinated roles of miR-26a and miR-30c in regulating TGFβ1-induced epithelial-to-mesenchymal transition in diabetic nephropathy

MicroRNAs (miRNAs) play vital roles in the development of diabetic nephropathy. Here, we compared the protective efficacies of miR-26a and miR-30c in renal tubular epithelial cells (NRK-52E) and determined whether they demonstrated additive effects in the attenuation of renal fibrosis. TGFβ1 suppressed miR-26a and miR-30c expression but up-regulated pro-fibrotic markers in NRK-52E cells, and these changes were also found in the kidney cortex of 40-week-old diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats. Bioinformatic analyses and luciferase assays further demonstrated that both miR-26a and miR-30c targeted connective tissue growth factor (CTGF); additionally, Snail family zinc finger 1 (Snail1), a potent epithelial-to-mesenchymal transition (EMT) inducer, was targeted by miR-30c. Overexpression of miR-26a and miR-30c coordinately decreased CTGF protein levels and subsequently ameliorated TGFβ1-induced EMT in NRK-52E cells. Co-silencing of miR-26a and miR-30c exhibited the opposite effect. Moreover, miR-26a and miR-30c co-silenced CTGF to decrease ERK1/2 and p38 MAPK activation. Furthermore, miR-26a was up-regulated in urinary extracellular vesicles of diabetic nephropathy patients. Our study provides evidence for the cooperative roles of miR-26a and miR-30c in the pathogenesis of diabetic nephropathy, and the co-targeting of miR-26a and miR-30c could provide a new direction for diabetic nephropathy treatment

Procedures for a dynamical system on {0,1} n with DNA molecules

Abstract In this paper, an improved form of DNA representations of elements in {0, 1} n , which was first proposed by Fujiwara et al. n is investigated by DNA molecules

miRNAs in Urine Extracellular Vesicles as Predictors of Early-Stage Diabetic Nephropathy

Background. miR-192, miR-194, and miR-215 are enriched in the kidney and play roles in the pathogenesis of diabetic nephropathy (DN). Extracellular vesicles (EVs) can be detected in body fluids and may serve as disease biomarkers. Methods. Eighty type 2 diabetes patients with normoalbuminuria (n=30), microalbuminuria (n=30), or macroalbuminuria (n=20), as well as 10 healthy controls, were enrolled in this study. Real-time PCR was used to evaluate urinary EV miRNAs expression. Results. The miR-192 levels were significantly higher than the miR-194 and miR-215 levels in urine EVs and all three miRNAs were significantly increased in the microalbuminuric group compared with the normoalbuminuric and control subjects but were decreased in the macroalbuminuric group. In patients with normoalbuminuria and microalbuminuria, miR-192 was positively correlated with albuminuria (r=0.357, P=0.005) levels and transforming growth factor- (TGF-) β1 (r=0.356, P=0.005) expression. Receiver operating characteristic (ROC) curve analysis revealed that miR-192 was better than miR-194 and miR-215 in discriminating the normoalbuminuric group from the microalbuminuric group. Exposure of human renal tubular epithelial cells to high glucose increased the expression of both miRNAs in cellular supernatant EVs, indicating a potential source. Conclusion. These results suggest the potential use of urinary EV miR-192 as a biomarker of the early stage of DN

Measurement of the neutron total cross sections of aluminum at the back-n white neutron source of CSNS

Aluminum and its alloys are widely used in the nuclear industry. Therefore, it is essential to precisely measure and accurately know the neutron total cross section of aluminum in the wider energy region. The measurement is performed by using the transmission method at the Back-n White Neutron Source of CSNS. Two aluminum samples 70 mm in diameter and thicknesses of 40 and 60 mm, respectively, were positioned at 55 m from the neutron source. The transmission detector consisted of a multi-layer fast fission chamber loaded with $$^{235}$$U and $$^{238}$$U, and it was located at the 76-m measurement station. By applying the time-of-flight technique, it was possible to extract the n+$$^{27}$$Al total cross section in a wide energy region, from 1 eV to 20 MeV, after the correction for the double-bunch mode of the CSNS accelerator. The total cross sections obtained with the two Al samples are consistent and the results obtained with the $$^{235}$$U fission cells are in good agreement with that with $$^{238}$$U in the energy range of 1–20 MeV. The uncertainty of neutron total cross section measured with $$^{235}$$U for 40 mm and 60 mm thick aluminum is 0.7–22.3% and 0.6–12.4% in the energy range of 10 keV–20 MeV. Results are in fair agreement with respect to previous data and evaluations

Measurement of Gamma-Ray from Inelastic Neutron Scattering on 56Fe

In nuclear reactors, inelastic neutron scattering is a significant energy-loss mechanism which has deep impacts on designments of nuclear reactor and radiation shielding. Iron is an important material in reactor. However, for the existing nuclear data for iron, there exists an obvious divergence for the inelastic scattering cross sections and the related gamma production sections. Therefore the precise measurements are urgently needed for satisfying the demanding to design new nuclear reactors (fast reactors), Accelerator Driven Subcritical System (ADS), and other nuclear apparatus. In this paper, we report a new system with an array of HPGe detectors, electronics and acquisition system. Experiments had been carried out on three neutron facilities