The value of IGF-1 and IGFBP-1 in patients with heart failure with reduced, mid-range, and preserved ejection fraction

Background: Previous studies have reported inconsistent results regarding the implications of deranged insulin-like growth factor 1 (IGF-1)/insulin-like growth factor-binding protein 1 (IGFBP-1) axis in patients with heart failure (HF). This study evaluates the roles of IGF1/IGFBP-1 axis in patients with HF with reduced ejection fraction (HFrEF), mid-range ejection fraction (HFmrEF), or preserved ejection fraction (HFpEF). Methods: Consecutive patients with HFrEF, HFmrEF, and HFpEF who underwent comprehensive cardiac assessment were included. The primary endpoint was the composite endpoint of all-cause death and HF rehospitalization at one year. Results: A total of 151 patients with HF (HFrEF: n = 51; HFmrEF: n = 30; HFpEF: n = 70) and 50 control subjects were included. The concentrations of IGFBP-1 (p < 0.001) and IGFBP-1/IGF-1 ratio (p < 0.001) were significantly lower in patients with HF compared to controls and can readily distinguish patients with and without HF (IGFBP-1: areas under the curve (AUC): 0.725, p < 0.001; IGFBP-1/IGF-1 ratio: AUC:0.755, p < 0.001; respectively). The concentrations of IGF-1, IGFBP-1, and IGFBP-1/IGF-1 ratio were similar among HFpEF, HFmrEF, and HFrEF patients. IGFBP-1 and IGFBP-1/IGF-1 ratio positively correlated with N-terminal probrain natriuretic peptide (NT-proBNP) levels (r = 0.255, p = 0.002; r = 0.224, p = 0.007, respectively). IGF-1, IGFBP-1, and IGFBP-1/IGF-1 ratio did not predict the primary endpoint at 1 year for the whole patients with HF and HF subtypes on both univariable and multivariable Cox regression. Conclusion: The concentrations of plasma IGFBP-1 and IGFBP-1/IGF-1 ratio can distinguish patients with and without HF. In HF, IGFBP-1 and IGFBP-1/IGF-1 ratio positively correlated with NT-proBNP levels

Fatigue crack propagation behavior of Ni-based superalloys after overloading at elevated temperatures

AbstractThe fatigue crack propagation behavior of three superalloys subjected to a single overloading at elevated temperatures was investigated. The fatigue crack propagation rate FCPR versus stress intensity factor range data da/dN—ΔK were calculated using the two-point secant method. It was found that the crack growth rates of the investigated materials were retarded after overloading with an overload ratio ROL=1.6. The size of the plastic zone in the front of the crack tip and its relation to loading level were discussed. The overload retardation effects are attributed to crack closure. The fatigue damage in the plastic zone can also be a factor to explain the overload retardation

The Value of IGF-1 and IGFBP-1 in Patients With Heart Failure With Reduced, Mid-range, and Preserved Ejection Fraction

Background: Previous studies have reported inconsistent results regarding the implications of deranged insulin-like growth factor 1 (IGF-1)/insulin-like growth factor-binding protein 1 (IGFBP-1) axis in patients with heart failure (HF). This study evaluates the roles of IGF1/IGFBP-1 axis in patients with HF with reduced ejection fraction (HFrEF), mid-range ejection fraction (HFmrEF), or preserved ejection fraction (HFpEF). Methods: Consecutive patients with HFrEF, HFmrEF, and HFpEF who underwent comprehensive cardiac assessment were included. The primary endpoint was the composite endpoint of all-cause death and HF rehospitalization at one year. Results: A total of 151 patients with HF (HFrEF: n = 51; HFmrEF: n = 30; HFpEF: n = 70) and 50 control subjects were included. The concentrations of IGFBP-1 (p < 0.001) and IGFBP-1/IGF-1 ratio (p < 0.001) were significantly lower in patients with HF compared to controls and can readily distinguish patients with and without HF (IGFBP-1: areas under the curve (AUC): 0.725, p < 0.001; IGFBP-1/IGF-1 ratio: AUC:0.755, p < 0.001; respectively). The concentrations of IGF-1, IGFBP-1, and IGFBP-1/IGF-1 ratio were similar among HFpEF, HFmrEF, and HFrEF patients. IGFBP-1 and IGFBP-1/IGF-1 ratio positively correlated with N-terminal probrain natriuretic peptide (NT-proBNP) levels (r = 0.255, p = 0.002; r = 0.224, p = 0.007, respectively). IGF-1, IGFBP-1, and IGFBP-1/IGF-1 ratio did not predict the primary endpoint at 1 year for the whole patients with HF and HF subtypes on both univariable and multivariable Cox regression. Conclusion: The concentrations of plasma IGFBP-1 and IGFBP-1/IGF-1 ratio can distinguish patients with and without HF. In HF, IGFBP-1 and IGFBP-1/IGF-1 ratio positively correlated with NT-proBNP levels

Cardiac arrhythmias in patients with COVID-19.

The emergence of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a major global public health concern. Although SARS-CoV-2 causes primarily respiratory problems, concurrent cardiac injury cannot be ignored since it may be an independent predictor for adverse outcomes. Cardiac arrhythmias are often observed in patients with COVID-19, especially in severe cases, and more likely contribute to the high risk of adverse outcomes. Arrhythmias should be regarded as one of the main complications of COVID-19. Mechanistically, a number of ion channels can be adversely affected in COVID-19, leading to alterations in cardiac conduction and/or repolarization properties, as well as calcium handling, which can predispose to cardiac arrhythmogenesis. In addition, several antimicrobials that are currently used as potential therapeutic agents for COVID-19, such as chloroquine, hydroxychloroquine and azithromycin, have uncertain benefit, and yet may induce electrocardiographic QT prolongation with potential ventricular pro-arrhythmic effects. Continuous electrocardiogram monitoring, accurate and prompt recognition of arrhythmias are important. The present review focuses on cardiac arrhythmias in patients with COVID-19, its underlying mechanisms, and proposed preventive and therapeutic strategies

RNA-seq analysis of glycosylation related gene expression in STZ-induced diabetic rat kidney inner medulla

The UT-A1 urea transporter is crucial to the kidney’s ability to generate concentrated urine. Native UT-A1 from kidney inner medulla (IM) is a heavily glycosylated protein with two glycosylation forms of 97 and 117 kDa. In diabetes, UT-A1 protein abundance, particularly the 117 kD isoform, is significantly increased corresponding to an increased urea permeability in perfused IM collecting ducts, which plays an important role in preventing the osmotic diuresis caused by glucosuria. However, how the glycan carbohydrate structure change and the glycan related enzymes regulate kidney urea transport activity, particularly under diabetic condition, is largely unknown. In this study, using sugar-specific binding lectins, we found that the carbohydrate structure of UT-A1 is changed with increased amounts of sialic acid, fucose, and increased glycan branching under diabetic conditions. These changes were accompanied by altered UT-A1 association with the galectin proteins, α-galactoside glycan binding proteins. To explore the molecular basis of the alterations of glycan structures, the highly sensitive next generation sequencing (NGS) technology, Illumina RNA-seq, was employed to analyze genes involved in the process of UT-A1 glycosylation using streptozotocin (STZ) - induced diabetic rat kidney. Differential gene expression analysis combining quantitative PCR revealed that expression of a number of important glycosylation related genes were changed under diabetic conditions. These genes include the glycosyltransferase genes Mgat4a, the sialylation enzymes St3gal1 and St3gal4 and glycan binding protein galectin-3, -5, -8 and -9. In contrast, although highly expressed in kidney IM, the glycosyltransferase genes Mgat1, Mgat2, and fucosyltransferase Fut8, did not show any changes. Conclusions: In diabetes, not only is UT-A1 protein abundance increased but the protein’s glycan structure is also significantly changed. UT-A1 protein becomes highly sialylated, fucosylated and branched. Consistently, a number of crucial glycosylation related genes are changed under diabetic conditions. The alteration of these genes may contribute to changes in the UT-A1 glycan structure and therefore modulate kidney urea transport activity and alleviate osmotic diuresis caused by glucosuria in diabetes

Curing hemophilia A by NHEJ-mediated ectopic F8 insertion in the mouse

BACKGROUND: Hemophilia A, a bleeding disorder resulting from F8 mutations, can only be cured by gene therapy. A promising strategy is CRISPR-Cas9-mediated precise insertion of F8 in hepatocytes at highly expressed gene loci, such as albumin (Alb). Unfortunately, the precise in vivo integration efficiency of a long insert is very low (~ 0.1%). RESULTS: We report that the use of a double-cut donor leads to a 10- to 20-fold increase in liver editing efficiency, thereby completely reconstituting serum F8 activity in a mouse model of hemophilia A after hydrodynamic injection of Cas9-sgAlb and B domain-deleted (BDD) F8 donor plasmids. We find that the integration of a double-cut donor at the Alb locus in mouse liver is mainly through non-homologous end joining (NHEJ)-mediated knock-in. We then target BDDF8 to multiple sites on introns 11 and 13 and find that NHEJ-mediated insertion of BDDF8 restores hemostasis. Finally, using 3 AAV8 vectors to deliver genome editing components, including Cas9, sgRNA, and BDDF8 donor, we observe the same therapeutic effects. A follow-up of 100 mice over 1 year shows no adverse effects. CONCLUSIONS: These findings lay the foundation for curing hemophilia A by NHEJ knock-in of BDDF8 at Alb introns after AAV-mediated delivery of editing components

characterization of pm1 bound metallic elements in the ambient air at a high mountain site in northern china

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Percutaneous Coronary Intervention Versus Medical Therapy for Chronic Total Occlusion of Coronary Arteries:A Systematic Review and Meta-Analysis

PURPOSE OF REVIEW: Chronic total occlusion (CTO) of the coronary arteries is a significant clinical problem and has traditionally been treated by medical therapy or coronary artery bypass grafting. Recent studies have examined percutaneous coronary intervention (PCI) as an alternative option. RECENT FINDINGS: This systematic review and meta-analysis compared medical therapy to PCI for treating CTOs. PubMed and Embase were searched from their inception to March 2019 for studies that compared medical therapy and PCI for clinical outcomes in patients with CTOs. Quality of the included studies was assessed by Newcastle-Ottawa scale. The results were pooled by DerSimonian and Laird random- or fixed-effect models as appropriate. Heterogeneity between studies and publication bias was evaluated by I2 index and Egger's regression, respectively. Of the 703 entries screened, 17 studies were included in the final analysis. This comprised 11,493 participants. Compared to PCI, medical therapy including randomized and observational studies was significantly associated with higher risk of all-cause mortality (risk ratio (RR) 1.99, 95% CI 1.38-2.86), cardiac mortality (RR 2.36 (1.97-2.84)), and major adverse cardiac event (RR 1.25 (1.03-1.51)). However, no difference in the rate of myocardial infarction and repeat revascularization procedures was observed between the two groups. Univariate meta-regression demonstrated multiple covariates as independent moderating factors for myocardial infarction and repeat revascularization but not cardiac death and all-cause mortality. However, when only randomized studies were included, there was no difference in overall mortality or cardiac death. In CTO, when considering randomized and observational studies, medical therapy might be associated with a higher risk of mortality and myocardial infarction compared to PCI treatment

Programmes for the prevention of mother-to-child HIV infection transmission have made progress in Yunnan Province, China, from 2006 to 2015: a cost effective and cost-benefit evaluation

Abstract Background Prevention of mother-to-child transmission (PMTCT) of HIV programmes have substantially reduced HIV infections among infants in Yunnan Province, China. We conducted a macro-level economic evaluation of Yunnan’s PMTCT programmes over the 10 years from 2006 to 2015 from a policymaker perspective. Methods The study methodology was in accordance with the guidelines from the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. We quantified the output from the Yunnan’s PMTCT programmes by estimating the number of paediatric HIV infections averted and the relative savings to both the health care system and society. The return-on-investment ratio (ROI) was calculated as the output (numerator) divided by the input (denominator). Results We have found that the US$49 million investment in Yunnan’s PMTCT programmes over the period from 2006 to 2015 averted an estimated 2725 new paediatric HIV infections and resulted in an estimated 134,008 QALY acquired. It saved an estimated US$ 0.5 billion in treatment expenditures for Yunnan’s healthcare system and nearly US$3.9 billion in productivity. The ROI was 88.4, meaning every US$ 1 invested brought about US$ 88.4 in benefits. Conclusions Our results support the ongoing investment in PMTCT programmes in Yunnan Province. The PMTCT strategy is a cost effective and cost-benefit strategy in the periods from 2006 to 2015. Despite higher investments in the future, the overall investment in the PMTCT programmes in Yunnan province could be offset by averting more paediatric infections