Risk assessment of failure during transitioning from in-centre to home haemodialysis

Background: Introducing a de-novo home haemodialysis (HHD) program often raises safety concerns as errors could potentially lead to serious adverse events. Despite the complexity of performing haemodialysis at home without the supervision of healthcare staff, HHD has a good safety record. We aim to pre-emptively identify and reduce the risks to our new HHD program by risk assessment and using failure mode and effects analysis (FMEA) to identify potential defects in the design and planning of HHD. Methods: We performed a general risk assessment of failure during transitioning from in-centre to HHD with a failure mode and effects analysis focused on the highest areas of failure. We collaborated with key team members from a well-established HHD program and one HHD patient. Risk assessment was conducted separately and then through video conference meetings for joint deliberation. We listed all key processes, sub-processes, step and then identified failure mode by scoring based on risk priority numbers. Solutions were then designed to eliminate and mitigate risk. Results: Transitioning to HHD was found to have the highest risk of failure with 3 main processes and 34 steps. We identified a total of 59 areas with potential failures. The median and mean risk priority number (RPN) scores from failure mode effect analysis were 5 and 38, with the highest RPN related to vascular access at 256. As many failure modes with high RPN scores were related to vascular access, we focussed on FMEA by identifying the risk mitigation strategies and possible solutions in all 9 areas in access-related medical emergencies in a bundled- approach. We discussed, the risk reduction areas of setting up HHD and how to address incidents that occurred and those not preventable. Conclusions: We developed a safety framework for a de-novo HHD program by performing FMEA in high-risk areas. The involvement of two teams with different clinical experience for HHD allowed us to successfully pre-emptively identify risks and develop solutions

Denervation as a Common Mechanism Underlying Different Pulmonary Vein Isolation Strategies for Paroxysmal Atrial Fibrillation: Evidenced by Heart Rate Variability after Ablation

Backgrounds. Segmental and circumferential pulmonary vein isolations (SPVI and CPVI) have been demonstrated to be effective therapies for paroxysmal atrial fibrillation (PAF). PVI is well established as the endpoint of different ablation techniques, whereas it may not completely account for the long-term success. Methods. 181 drug-refractory symptomatic PAF patients were referred for segmental or circumferential PVI (SPVI = 67; CPVI = 114). Heart rate variability (HRV) was assessed before and after the final ablation. Results. After following up for 62.23±12.75 months, patients underwent 1.41±0.68 procedures in average, and the success rates in SPVI and CPVI groups were comparable. 119 patients were free from AF recurrence (SPVI-S, n=43; CPVI-S, n=76). 56 patients had recurrent episodes (SPVI-R, n=21; CPVI-R, n=35). Either ablation technique decreased HRV significantly. Postablation SDNN and rMSSD were significantly lower in SPVI-S and CPVI-S subgroups than in SPVI-R and CPVI-R subgroups (SPVI-S versus SPVI-R: SDNN 91.8±32.6 versus 111.5±36.2 ms, rMSSD 47.4±32.3 versus 55.2±35.2 ms; CPVI-S versus CPVI-R: SDNN 83.0±35.6 versus 101.0±40.7 ms, rMSSD 41.1±22.9 versus 59.2±44.8 ms; all P<0.05). Attenuation of SDNN and rMSSD remained for 12 months in SPVI-S and CPVI-S subgroups, whereas it recovered earlier in SPVI-R and CPVI-R subgroups. Multivariate logistic regression analysis identified SDNN as the only predictor of long-term success. Conclusions. Beyond PVI, denervation may be a common mechanism underlying different ablation strategies for PAF

Elevated expression of p53 gain-of-function mutation R175H in endometrial cancer cells can increase the invasive phenotypes by activation of the EGFR/PI3K/AKT pathway

<p>Abstract</p> <p>Background</p> <p>p53 is the most commonly mutated tumor suppressor gene in human cancers. In addition to the loss of tumor suppression function and exertion of dominant-negative effects over the remaining wild-type protein, several p53 mutants can gain novel oncogenic functions (gain-of-function, GOF) that actively regulate cancer development and progression. In human endometrial cancer, p53 mutation is more often associated with aggressive nonendometrioid cancer. However, it was unknown if p53 mutants contributed to endometrial cancer progression through the GOF properties.</p> <p>Methods</p> <p>To clarify the relationship between expression of p53 GOF mutation (p53-R175H) and invasive potential of human endometrial cancer KLE cells, we tested the consequences of up-regulation and down-regulation of p53-R175H in KLE cells by inducing p53-R175H expression vector or suppressing the p53 gene with short hairpin RNA.</p> <p>Results</p> <p>We found that forced over-expression of p53-R175H significantly promoted cell migration and invasion, and induced activation of the epidermal growth factor receptor (EGFR)/phosphatidylinositol 3-kinase (PI3K)/AKT pathway. Conversely, suppression of p53-R175H with short hairpin RNA significantly inhibited cell migration and invasion, and resulted in attenuation of EGFR/PI3K/AKT pathway.</p> <p>Conclusion</p> <p>These findings show for the first time that elevated expression of p53-R175H mutant may exert gain-of-function activity to activate the EGFR/PI3K/AKT pathway and thus may contribute to the invasive phenotype in endometrial cancer.</p

Quasi proportional-resonant control for the grid current of hybrid distribution transformer

Hybrid distribution transformer (HDT) has powerful control ability, which is significant for the intelligentisation of the distribution network. A kind of HDT is presented here, the grid current control system of which is emphatic researched. Based on the mathematical model of ideal HDTs, a grid current control system is designed with quasi proportional-resonant controller (QPR). Using the characteristics that infinite gain and large bandwidth at the resonant frequency of QPR controller, the grid current system achieve the effects of unit power factor and sinusoidal symmetrical waveform. Tracking control with no static error of grid current was achieved in MATLAB. Compared with the traditional PI control, QPR controller can modulate AC signals in the static coordinate system, rather than rotary coordinate system. So the QPR controller has advantages of lower steady-state error, stronger anti-interference ability, and simpler calculation. Simulation results show that it has good dynamic and steady performance

Knockout of MTF1 Inhibits the Epithelial to Mesenchymal Transition in Ovarian Cancer Cells

Due to peritoneal metastasis and frequent recurrence, ovarian cancer has the highest mortality among gynecological cancers. Epithelial to mesenchymal transition (EMT) contributes to ovarian tumor metastasis. In this study, we report for the first time that metal regulatory transcription factor 1 (MTF1) was upregulated in ovarian cancer, and its high expression was associated with poor patient survival and disease relapse. Knockout of MTF1 using lentiviral CRISPR/Cas9 nickase vector-mediated gene editing inhibited EMT by upregulating epithelial cell markers E-cadherin and cytokeratin 7, and downregulating mesenchymal markers Snai2 and β-catenin in ovarian cancer SKOV3 and OVCAR3 cells. Loss of MTF1 reduced cell proliferation, migration, and invasion in both SKOV3 and OVCAR3 cells. Knockout of MTF1 upregulated the expression of the KLF4 transcription factor, and attenuated two cellular survival pathways, ERK1/2 and AKT. Our studies demonstrated that MTF1 plays an oncogenic role and contributes to ovarian tumor metastasis by promoting EMT. MTF1 may be a novel biomarker for early diagnosis as well as a drug target for clinical therapy

Prevalence of cognitive impairment and its predictors among chronic kidney disease patients: A systematic review and meta-analysis.

BackgroundCognitive impairment (CI) is common among patients with chronic kidney disease (CKD), and is associated with a poor prognosis. We assessed the prevalence and associated factors of CI in patients with CKD.MethodsA systematic review and meta-analysis were conducted by searching PubMed, Embase, and the Web of Science through December 1, 2023. Random effects models were performed with subgroup analyses to further explore the heterogeneity.Results50 studies involving 25,289 CKD patients were included. The overall prevalence of CI was 40% (95% confidence interval 33-46). The pooled prevalence of CI was relatively higher in CKD patients from Africa (58%), Asia (44%) and America (37%). Attention and executive dysfunction appeared to be the most common manifestations. The prevalence of CI was higher among patients with hemodialysis (53%) and peritoneal dialysis (39%) than those without dialysis (32%) and post-kidney transplanted (26%). In addition, advanced age, the presence of diabetes and hypertension might increase the risk of CI in CKD patients.ConclusionsPeople with CKD have a high prevalence of CI, especially in patients with hemodialysis. An early and comprehensive screening for CI in CKD patients is needed to improve clinical outcomes.Trial registrationRegistration number: PROSPERO (CRD42023412864)

Co-occurrence patterns among prokaryotes across an age gradient in pit mud of Chinese strong-flavor liquor

It is widely believed that the quality and characteristics of Chinese strong-flavor liquor (CSFL) are closely related to the age of the pit mud; CSFL produced from older pit mud tastes better. This study aimed to investigate the alteration and interaction of prokaryotic communities across an age gradient in pit mud. Prokaryotic microbes in different-aged pit mud (1, 6, and 10 years old) were analyzed by Illumina MiSeq sequencing of the 16S rRNA gene. Analysis of the 16S rRNA gene indicated that the prokaryotic community was significantly altered with pit mud age. There was a significant increase in the genera Methanosarcina, Methanobacterium, and Aminobacterium with increased age of pit mud, while the genus Lactobacillus showed a significant decreasing trend. Network analysis demonstrated that both synergetic co-occurrence and niche competition were dominated by 68 prokaryotic genera. These genera formed 10 hubs of co-occurrence patterns, mainly under the phyla Firmicutes, Euryarchaeota, and Bacteroidetes, playing important roles on ecosystem stability of the pit mud. Environmental variables (pH, NH4+, available P, available K, and Ca2+) correlated significantly with prokaryotic community assembly. The interaction of prokaryotic communities in the pit mud ecosystem and the relationship among prokaryotic communities and environmental factors contribute to the higher quality of the pit mud in older fermentation pits.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Catalytic oxidation of 5-hydroxymethylfurfural to 2,5-furandicarboxylic acid using Co-N/C catalysts with stepwise base addition approach

The production of 2,5-furandicarboxylic acid (FDCA) through green reaction routes is of crucial scientific value for the production of sustainable polymers. This study explores the active centers in cobalt-nitrogen-doped carbon (Co-N/C) for FDCA production. It was established that Co-Nx synergistically along with the nitrogen-doped carbon acted as centers for 5-hydroxymethylfurfural (HMF) oxidation. This study demonstrates a sustainable method for FDCA production from HMF without using precious metals, organic solvents, and harsh basic environments. Co-N/C catalyst displayed a high FDCA yield of ∼90% in an aqueous medium under mildly basic conditions in 34 h with 100% HMF conversion. An innovative strategy of stepwise base addition has been proposed to effectively accelerate the generation reaction of FDCA. The detrimental effects of high heating rate and calcination temperature on the active centers were also thoroughly investigated. Through DFT simulations it was established that Co-Nx aided in the activation of oxygen for HMF oxidation