Exploring the Role of Guidelines in Contributing to Medication Errors: A Descriptive Analysis of National Patient Safety Incident Data.

INTRODUCTION: Clinical guidelines can contribute to medication errors but there is no overall understanding of how and where these occur. OBJECTIVES: We aimed to identify guideline-related medication errors reported via a national incident reporting system, and describe types of error, stages of medication use, guidelines, drugs, specialties and clinical locations most commonly associated with such errors. METHODS: Retrospective analysis of reports to the National Reporting and Learning System for England and Wales. A hierarchical task analysis (HTA) was developed, describing expected practice when using guidelines. A free-text search was conducted of medication incident reports (2016-2021) using search terms related to common guidelines. All identified reports linked to moderate-severe harm or death, and a random sample of 5100 no/low-harm reports were coded to describe deviations from the HTA. A random sample of 500 cases were independently double-coded. RESULTS: In total, 28,217 reports were identified, with 608 relating to moderate-severe harm or death. Fleiss' kappa for interrater reliability was 0.46. Of the 5708 reports coded, 642 described an HTA step discrepancy (including four linked to a death), suggesting over 3200 discrepancies in the entire dataset of 28,217 reports. Discrepancies related to finding guidelines (n = 300 reports), finding information within guidelines (n = 166) and using information (n = 176). Discrepancies were most frequently identified for guidelines produced by a local organisation (n = 405), and most occurred during prescribing (n = 277) or medication administration (n = 241). CONCLUSION: Difficulties finding and using information from clinical guidelines contribute to thousands of prescribing and medication administration incidents, some of which are associated with substantial patient harm.

ZNF667 Suppressed LPS-induced Macrophages Inflammation through mTOR-dependent Aerobic Glycolysis Regulation.

BACKGROUND: Macrophages participate in all stages of the inflammatory response, and the excessive release of inflammatory mediators and other cytokines synthesized and secreted by macrophages is fundamentally linked to an uncontrolled inflammatory response. The zinc finger 667 (ZNF667) protein, a novel DNAbinding protein, has been shown to play a vital role in oxidative stress. However, none of the target genes in macrophages or the potential roles of ZNF667 have been elucidated to date. > Objectives: The present study was designed to investigate the effects of ZNF667 on LPS-induced inflammation in macrophages. > Methods: The RAW264.7 macrophage cell line was selected as a model system. Inflammatory response-related gene expression levels and phosphorylation levels of PI3K, AKT, and mTOR were detected in LPS-treated macrophages via RT-PCR and western blotting, respectively. > Results: We found that LPS resulted in the up-regulation of ZNF667 in macrophages and a peak response in ZNF667 protein expression levels when used at a concentration of 100 ng/mL. ZNF667 overexpression significantly inhibited the LPS-induced up-regulation of iNOS, and IL-1ß mRNA and protein expression levels, together with the secretion of IL-1ß, IL-6, and TNF-α. ZNF667 overexpression also inhibited PI3K, AKT, and mTOR hyperphosphorylation and had no effect on the phosphorylation of NF-κB p65, ERK1/2, MAPK p38, and the transcriptional activity of NF-κB in macrophages. The up-regulation of ZNF667 inhibited the levels of expression of HK2 and PFKFB3, glucose consumption, and lactate production in LPS-stimulated macrophages. The up-regulation of mRNA levels of LPS-induced glycolytic genes HK2 and PFKFB3 and the increased mRNA expression of pro-inflammatory cytokines (IL-1ß and iNOS) were abolished by hexokinase inhibitor 2-DG in ZNF667-deficient macrophages. Meanwhile, glucose consumption and lactate production were abrogated in macrophages when cells were treated with the specific mTOR inhibitor RPM. > Conclusion: Our results demonstrate that ZNF667 suppressed LPS-stimulated RAW264.7 macrophage inflammation by regulating mTOR-dependent aerobic glycolysis.>.

S100 proteins in atherosclerosis.

Atherosclerosis is an arterial disease associated with dyslipidemia, abnormal arterial calcification and oxidative stress. It has been shown that a continued chronic inflammatory state of the arterial wall contributes to the development of atherosclerosis. The inflammatory stimulation, recruitment of inflammatory cells and production of pro-inflammatory cytokines enhances vascular inflammation. Some members of the S100 proteins family bind with their receptors, such as advanced glycation end products (RAGE), scavenger receptors (CD36) and toll-like receptor 4 (TLR-4), contributing to the cellular response in atherosclerotic progression. This review summarizes the roles of S100 proteins (S100A8, S100A9 and S100A12) in the vascular inflammation, vascular calcification and vascular oxidative stress. S100 proteins are released from monocytes, smooth muscle cells and endothelial cells in response to cellular stress stimuli, and then the binding of S100 proteins to RAGE activate downstream signaling such as transcription factor kappa B (NF-κB) translocation and reactive oxygen species (ROS) production, which act as a positive feedback loop for inducing pro-inflammatory phenotype in a wide variety of cell types including endothelial cells, vascular smooth muscle cells and leukocytes. Thus, it suggests that the inhibition of S100 proteins-mediated RAGE and TLR4 activation appears to be a promising approach to treat atherosclerosis. In addition, recent study showed that serum S100A12 can predict future cardiovascular events, highlighting that S100A12 is likely to be a potential biomarker of therapeutic efficacy and disease progression in coronary heart disease. Future studies of patients with coronary heart disease may provide more evidences supporting that S100 proteins is promising drug target in the prevention and therapy of atherosclerosis.

The emerging roles of extracellular vesicles in diabetes and diabetic complications.

Diabetes and diabetic vascular complications are now the leading cause of death in the world. The effects of traditional medical treatment are usually limited and accompanied by many side effects, such as hypoglycemia, obesity, liver and kidney damage, and gastrointestinal adverse reactions. Thus, it is urgent to explore some new strategies for the treatment of patients with diabetes. Recently, extracellular vesicles have received increased attention because of their emerging roles of cell-to-cell communication under physiological and pathological conditions. In addition, because of their abundant existence in almost all body fluids, as well as their plentiful cargos of bioactive proteins and miRNAs they carry, extracellular vesicles have a strong potential for therapeutic and diagnostic applications in many metabolic diseases, such as obesity and insulin resistance. Here, with the aim of providing the basis for the development of new treatments for diabetes, we review current understanding of extracellular vesicles and the critical roles it has played in the onset and progression of diabetes and diabetic complications.

Defective trafficking of Kv2.1 channels in MPTP-induced nigrostriatal degeneration.

Intracellular protein trafficking is tightly regulated, and improper trafficking might be the fundamental provocateur for human diseases including neurodegeneration. In neurons, protein trafficking to and from the plasma membrane affects synaptic plasticity. Voltage-gated potassium channel 2.1 (Kv2.1) is a predominant delayed rectifier potassium (K+ ) current, and electrical activity patterns of dopamine (DA) neurons within the substantia nigra are generated and modulated by the orchestrated function of different ion channels. The pathological hallmark of Parkinson's disease (PD) is the progressive loss of these DA neurons, resulting in the degeneration of striatal dopaminergic terminals. However, whether trafficking of Kv2.1 channels contributes to PD remains unclear. In this study, we demonstrated that MPTP/MPP+ increases the surface expression of the Kv2.1 channel and causes nigrostriatal degeneration by using a subchronic MPTP mouse model. The inhibition of the Kv2.1 channel by using a specific blocker, guangxitoxin-1E, protected nigrostriatal projections against MPTP/MPP+ insult and thus facilitated the recovery of motor coordination. These findings highlight the importance of trafficking of Kv2.1 channels in the pathogenesis of PD.

Design and fabrication of single-walled carbon nanonet flexible strain sensors.

This study presents a novel flexible strain sensor for real-time strain sensing. The material for strain sensing is single-walled carbon nanonets, grown using the alcohol catalytic chemical vapor deposition method, that were encapsulated between two layers of Parylene-C, with a polyimide layer as the sensing surface. All of the micro-fabrication was compatible with the standard IC process. Experimental results indicated that the gauge factor of the proposed strain sensor was larger than 4.5, approximately 2.0 times greater than those of commercial gauges. The results also demonstrated that the gauge factor is small when the growth time of SWCNNs is lengthier, and the gauge factor is large when the line width of the serpentine pattern of SWCNNs is small.