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Clonal hematopoiesis driven by somatic mutations in hematopoietic cells, frequently called clonal hematopoiesis of indeterminate potential (CHIP), has been associated with adverse cardiovascular outcomes in population-based studies and in patients with ischemic heart failure (HF) and reduced left ventricular ejection fraction (LVEF). Yet, the impact of CHIP on HF progression, including nonischemic etiology, is unknown.
The purpose of this study was to assess the clinical impact of clonal hematopoiesis on HF progression irrespective of its etiology.
The study cohort comprised 62 patients with HF and LVEF<45% (age 74 ± 7 years, 74% men, 52% nonischemic, and LVEF 30 ± 8%). Deep sequencing was used to detect CHIP mutations with a variant allelic fraction >2% in 54 genes. Nicotinamide Patients were followed for at least 3.5 years for various adverse events including death, HF-related death, and HF hospitalization.
CHIP mutations were detected in 24 (38.7%) patients, without significant differences in all-cause mo clonal hematopoiesis are common among HF patients with reduced LVEF and are associated with accelerated HF progression regardless of etiology.
The myocardium exhibits an adaptive tissue-specific renin-angiotensin system (RAS), and local dysbalance may circumvent the desired effects of pharmacologic RAS inhibition, a mainstay of heart failure with reduced ejection fraction (HFrEF) therapy.
This study sought to investigate human myocardial tissue RAS regulation of the failing heart in the light of current therapy.
Fifty-two end-stage HFrEF patients undergoing heart transplantation (no RAS inhibitor n=9; angiotensin-converting enzyme [ACE] inhibitor n=28; angiotensin receptor blocker [ARB] n=8; angiotensin receptor neprilysin-inhibitor [ARNi] n=7) were enrolled. Myocardial angiotensin metabolites and enzymatic activities involved in the metabolism of the key angiotensin peptides angiotensin 1-8 (AngII) and Ang1-7 were determined in left ventricular samples by mass spectrometry. Circulating angiotensin concentrations were assessed for a subgroup of patients.
AngII and Ang2-8 (AngIII) were the dominant peptides in the failing heart, while other mular structure. The results underline the importance of pharmacologic interventions reducing circulating AngII actions, yet offer room for cardiac tissue-specific RAS drugs aiming to limit myocardial AngII/AngIII peptide accumulation and actions.
The failing heart contains considerable levels of classical RAS metabolites, whereas AngIII might be an unrecognized mediator of detrimental effects on cardiovascular structure. link2 The results underline the importance of pharmacologic interventions reducing circulating AngII actions, yet offer room for cardiac tissue-specific RAS drugs aiming to limit myocardial AngII/AngIII peptide accumulation and actions.
Data on long-term cardiovascular outcomes in systemic lupus erythematosus (SLE) are sparse.
This study sought to examine the long-term risk and prognosis associated with cardiovascular outcomes, including heart failure (HF), in patients with SLE.
Using Danish administrative registries, risks of outcomes were compared between SLE patients (diagnosed 1996 to 2018, no history of cardiovascular disease) and age-, sex-, and comorbidity-matched control subjects from the background population (matched 14). Furthermore, mortality following HF diagnosis was compared between SLE patients developing HF and age- and sex-matched non-SLE control subjects with HF (matched 14).
A total of 3,411 SLE patients (median age 44.6 years [25th to 75th percentile 31.9 to 57.0 years]; 14.1% men) were matched with 13,644 control subjects. The median follow-up was 8.5 years (25th to 75th percentile 4.0 to 14.4 years). Absolute 10-year risks of outcomes were HF, 3.71% (95% confidence interval [CI] 3.02% to 4.51%) for SLE patientsoping HF, a history of SLE was associated with higher mortality.
SLE patients had a higher associated risk of HF and other cardiovascular outcomes compared with matched control subjects. Among patients developing HF, a history of SLE was associated with higher mortality.
Patients with rheumatic aortic stenosis (AS) were excluded from transcatheter aortic valve replacement (TAVR) trials.
The authors sought to examine outcomes with TAVR versus surgical aortic valve replacement (SAVR) in patients with rheumatic AS, and versus TAVR in nonrheumatic AS.
The authors identified Medicare beneficiaries who underwent TAVR or SAVR from October 2015 to December 2017, and then identified patients with rheumatic AS using prior validated International Classification of Diseases, Version 10 codes. Overlap propensity score weighting analysis was used to adjust for measured confounders. The primary study outcome was all-cause mortality. Multiple secondary outcomes were also examined.
The final study cohort included 1,159 patients with rheumatic AS who underwent aortic valve replacement (SAVR, n=554; TAVR, n=605), and 88,554 patients with nonrheumatic AS who underwent TAVR. Patients in the SAVR group were younger and with lower prevalence of most comorbidities and frailty scores. After median follow-up of 19months (interquartile range 13 to 26months), there was no difference in all-cause mortality with TAVR versus SAVR (11.2 vs. 7.0 per 100 person-year; adjusted hazard ratio 1.53; 95% confidence interval 0.84 to 2.79; p=0.2). Comparedwith TAVR in nonrheumatic AS, TAVR for rheumatic AS was associated with similar mortality (15.2 vs. 17.7 deaths per 100 person-years (adjusted hazard ratio 0.87; 95% confidence interval 0.68 to 1.09; p=0.2) after median follow-up of 17months (interquartile range 11 to 24months). None of the rheumatic TAVR patients,<11 SAVR patients, and 242 nonrheumatic TAVR patients underwent repeat aortic valve replacement (124 redo-TAVR and 118 SAVR) at follow-up.
Compared with SAVR, TAVR could represent a viable and possibly durable option for patients with rheumatic AS.
Compared with SAVR, TAVR could represent a viable and possibly durable option for patients with rheumatic AS.Tracking and quantifying hypochlorite (ClO-) in biological systems and environments remain challenging tasks, and many efforts have been made to improve ClO- recognition performance by modifying the sensor structure. In this study, a pre-designed coumarin/furanohydrazide-based sensor (CMFH) with the coumarin moiety as the building block (fluorogen) was rationally prepared as a ratiometric and colorimetric chemosensor for ClO- recognition. As expected, CMFH demonstrated excellent sensitivity and selectivity for ClO- detection. The fluorescence signal ratio (F466/F556) showed strong ClO- dependency, and the sensor exhibited ultrafast detection (within 60 s) and a low detection limit of 563 nM. Due to its low cytotoxicity and good tissue permeability, CMFH was demonstrated as a dual-channel sensor for ClO- bioimaging and visualization in cells, zebrafish, and even bacteria. Furthermore, CMFH-loaded paper strips were successfully applied to the colorimetric and fluorescent visualization of ClO-. The results demonstrate that CMFH has potential application value for tracking ClO- in various biosystems and environments.It is of great significance to develop facile and economical strategies for on-site detection and treatment of toxic metal ions. Stimulus-responsive DNA hydrogel materials have been increasingly used for convenient detection of metal ions due to their advantages such as simplicity, portability, and ease of storage. However, these methods still require encapsulation of signal tags by labeling or embedding. link3 In this paper, a one-step preparation of Pb2+-responsive pure DNA hydrogel material was designed to realize a new label-free strategy for Pb2+ biosensing. The Pb2+-dependent DNAzyme strand and substrate strand were introduced to fabricate the DNA hydrogel. The presence of Pb2+ in the sample activates the enzyme strand in the hydrogel skeleton and triggers the cleavage of the substrate, thereby destroy the hydrogel structure. DNA fragments released by the collapsed hydrogel were readily measured as signal output for quantifying Pb2+ concentrations with a minimum detection limit of 7.7 nM. We successfully eliminated the need for embedding or labeling of signal molecules by using the DNA molecules that construct hydrogels as the signal output. And the newly developed method for label-free detection of Pb2+ based on pure DNA hydrogel is simple, easy readout, and cost-effective. By adjusting the DNAzyme and substrate sequences, label-free analysis of other metal ions can also be achieved. We expect that our strategy can be applied to the field detection of toxic metal ions.Exosomal microRNAs (miRNAs) derived from different cells are proposed to be important noninvasive biomarkers for the diagnosis of cardiovascular disease. Recently, sensitive and reliable sensing of exosomal miRNAs has been garnered significant attention. Herein, a novel electrochemical biosensor based on a step polymerization catalytic hairpin assembly (SP-CHA) circuit is designed for exosomal miR-181 detection. Exosomal miR-181 as a trigger, induced SP-CHA process and generated a large number of T shaped concatemers with different length on the electrode surface. These ultra-concatemers could provide a much enhanced signal-to-noise ratio with the linear range from 10 fM to 100 nM and the detection limit of 7.94 fM. Furthermore, this assay was successfully applied to the detection of exosomal miR-181 in serum samples of normal healthy controls and patients with coronary heart disease (CHD) and the results were consistent with those analysis collected from qRT-PCR. The assembly demonstrated great performance in differentiating CHD patients from healthy controls (AUC0.9867). Collectively, this sensing system possessed high stability and sensitivity with ease of operation and cost efficiency, leading to great potential for exosomal miRNAs detection in cardiovascular disease.Quantification of ultra-trace inorganic and organic species of lead and mercury in unpolluted environmental water is crucial to estimate the mobility, toxicity and bioavailability and interactions. Simultaneous pre-concentration of Pb and Hg species in pg L-1 levels followed by multi-elemental speciation analysis makes great sense to a large set of unstable samples because of time advantages. Herein simultaneous enrichment and speciation analysis of ultra-trace lead and mercury in water was developed by online solid-phase extraction coupled with high performance liquid chromatography and inductively coupled plasma mass spectrometry (SPE-HPLC-ICP-MS) for this aim. Pb(II), trimethyl lead (TML), triethyl lead (TEL), Hg(II), methylmercury (MeHg) and ethylmercury (EtHg) were baseline separated in 11 min under gradient elution using 5 mM l-cysteine (Cys) at pH 2.5 in the 0-1 and 4-15 min and 5 mM Cys + 0.5 mM tetrabutyl ammonium hydroxide solution at pH 2.5 in the 1-4 min. Lead and mercury species in 10 mL intact water samples were adsorbed on a 1 cm C18 enrichment column pre-conditioned with 10 mL of 1 mM 2-mercaptoethanol at 10 mL min-1, and then directly desorbed by the mobile phases. High enrichment factors (459 for Pb(II), 1248 for TML, 1627 for TEL, 2485 for Hg(II), 1984 for MeHg and 1866 for EtHg) were obtained with good relative standard deviations ( less then 5%), leading to low LODs (0.001-0.011 ng L-1) and LOQs (0.004-0.036 ng L-1). Good accuracy of this method was validated by two certified reference materials of total lead in water (GBW08601) and total mercury in water (GBW08603) along with spiked recoveries (89-93%). The method was applied to analyze trace lead and mercury species in river, lake, tap and rain water, and purified and mineral water. Inorganic lead of 13-68 ng L-1 and inorganic mercury of 21-49 ng L-1 were measured in the nine water samples whereas TML, TEL and MeHg were not detected with 2-5 ng L-1 EtHg presented only in one river water and tap water.
My Website: https://www.selleckchem.com/products/Nicotinamide(Niacinamide).html
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