Комплексна оцінка рівня фінансової стійкості підприємства сфери послуг

Цель данной статьи заключается в обобщении теоретических основ и обоснование целесообразности применения комплексной оценки финансового состояния предприятия сферы услуг.Мета даної статті полягає в узагальненні теоретичних основ і обґрунтування доцільності застосування комплексної оцінки фінансового стану підприємства сфери послуг

Superimposed tissue formation in human aortic valve disease: differences between regurgitant and stenotic valves

The formation of superimposed tissue (SIT), a layer on top of the original valve leaflet, has been described in patients with mitral regurgitation as a major contributor to valve thickening and possibly as a result of increased mechanical stresses. However, little is known whether SIT formation also occurs in aortic valve disease. We therefore performed histological analyses to assess SIT formation in aortic valve leaflets (n = 31) from patients with aortic stenosis (n = 17) or aortic regurgitation due to aortic dilatation (n = 14). SIT was observed in both stenotic and regurgitant aortic valves, both on the ventricular and aortic sides, but with significant differences in distribution and composition. Regurgitant aortic valves showed more SIT formation in the free edge, leading to a thicker leaflet at that level, while stenotic aortic valves showed relatively more SIT formation on the aortic side of the body part of the leaflet. SIT appeared to be a highly active area, as determined by large populations of myofibroblasts, with varied extracellular matrix composition (higher collagen content in stenotic valves). Further, the identification of the SIT revealed the presence of foldings of the free edge in the diseased aortic valves. Insights into SIT regulation may further help in understanding the pathophysiology of aortic valve disease and potentially lead to the development of new therapeutic treatments.Cardiolog

Controlled delivery of gold nanoparticle-coupled miRNA therapeutics via an injectable self-healing hydrogel

Differential expression of microRNAs (miRNAs) plays a role in many diseases, including cancer and cardiovascular diseases. Potentially, miRNAs could be targeted with miRNA-therapeutics. Sustained delivery of these therapeutics remains challenging. This study couples miR-mimics to PEG-peptide gold nanoparticles (AuNP) and loads these AuNP-miRNAs in an injectable, shear thinning, self-assembling polymer nanoparticle (PNP) hydrogel drug delivery platform to improve delivery. Spherical AuNPs coated with fluorescently labelled miR-214 are loaded into an HPMC-PEG-b-PLA PNP hydrogel. Release of AuNP/miRNAs is quantified, AuNP-miR-214 functionality is shown in vitro in HEK293 cells, and AuNP-miRNAs are tracked in a 3D bioprinted human model of calcific aortic valve disease (CAVD). Lastly, biodistribution of PNP-AuNP-miR-67 is assessed after subcutaneous injection in C57BL/6 mice. AuNP-miRNA release from the PNP hydrogel in vitro demonstrates a linear pattern over 5 days up to 20%. AuNP-miR-214 transfection in HEK293 results in 33% decrease of Luciferase reporter activity. In the CAVD model, AuNP-miR-214 are tracked into the cytoplasm of human aortic valve interstitial cells. Lastly, 11 days after subcutaneous injection, AuNP-miR-67 predominantly clears via the liver and kidneys, and fluorescence levels are again comparable to control animals. Thus, the PNP-AuNP-miRNA drug delivery platform provides linear release of functional miRNAs in vitro and has potential for in vivo applications.publishersversionpublishe

Massive expansion and cryopreservation of functional human induced pluripotent stem cell-derived cardiomyocyte

Since the discovery of human induced pluripotent stem cells (hiPSCs), numerous strategies have been established to efficiently derive cardiomyocytes from hiPSCs (hiPSC-CMs). Here, we describe a cost-effective strategy for the subsequent massive expansion (>250-fold) of high-purity hiPSC-CMs relying on two aspects: removal of cell-cell contacts and small-molecule inhibition with CHIR99021. The protocol maintains CM functionality, allows cryopreservation, and the cells can be used in downstream assays such as disease modeling, drug and toxicity screening, and cell therapy. For complete details on the use and execution of this protocol, please refer to Buikema (2020)

Aortic valve visualization and pressurization device: a novel device for intraoperative evaluation of aortic valve repair procedures

OBJECTIVESAortic valve repair procedures are technically challenging, and current intraoperative evaluation methods often fail to predict the final echocardiographic result. We have developed a novel intraoperative aortic valve visualization and pressurization (AVP) device, enabling valve inspection under physiological conditions, and measuring aortic valve insufficiency (AI) during cardioplegic arrest.METHODSThe AVP device is attached to the (neo)aorta, after any type of aortic valve repair, while the heart is arrested. The root is pressurized (60–80 mmHg) using a saline solution and an endoscope is introduced. The valve is inspected, and the amount of valvular leakage is measured. Postoperative ‘gold standard’ transesophageal echocardiogram measurements of AI are performed and compared against regurgitation volume measured.RESULTSIn 24 patients undergoing valve-sparing root replacement, the AVP device was used. In 22 patients, postoperative echocardiographic AI was ≤ grade 1. The median leakage was 90 ml/min, IQR 60–120 ml/min. In 3 patients, additional adjustments after visual inspection was performed. In 2 patients, with complex anatomy, the valve was replaced. In one, after evaluation with the device, there was undesirable result visually and residual AI of 330 ml/min, and in another, 260 ml/min residual AI was measured and valve restriction on visual inspection.CONCLUSIONSThe novel AVP device enables intraoperative evaluation of the valve under physiological conditions, while still on arrested heart, and allows for targeted adjustments. The AVP device can be an important aid for intraoperative evaluation of the aortic valve, during valve repair and valve-sparing procedures, thereby making the operative result more predictable and the operation more efficient.Thoracic Surger

Anti-fibrotic Effects of Cardiac Progenitor Cells in a 3D-Model of Human Cardiac Fibrosis

Cardiac fibroblasts play a key role in chronic heart failure. The conversion from cardiac fibroblast to myofibroblast as a result of cardiac injury, will lead to excessive matrix deposition and a perpetuation of pro-fibrotic signaling. Cardiac cell therapy for chronic heart failure may be able to target fibroblast behavior in a paracrine fashion. However, no reliable human fibrotic tissue model exists to evaluate this potential effect of cardiac cell therapy. Using a gelatin methacryloyl hydrogel and human fetal cardiac fibroblasts (hfCF), we created a 3D in vitro model of human cardiac fibrosis. This model was used to study the possibility to modulate cellular fibrotic responses. Our approach demonstrated paracrine inhibitory effects of cardiac progenitor cells (CPC) on both cardiac fibroblast activation and collagen synthesis in vitro and revealed that continuous cross-talk between hfCF and CPC seems to be indispensable for the observed anti-fibrotic effect

High Serum Uric Acid Increases the Risk for Nonalcoholic Fatty Liver Disease: A Prospective Observational Study

Nonalcoholic fatty liver disease (NAFLD) is a common form of chronic liver disease, and serum uric acid is observed to be significantly elevated in NAFLD patients. However, whether this elevation is causal, a bystander, or a consequence of NAFLD remains unclear. We performed a population-based prospective study among the employees of Zhenhai Refining & Chemical Company Ltd., Ningbo, China to investigate whether the elevation of serum uric acid has a casual role for NAFLD. A total of 6890 initially NAFLD-free subjects were followed up for 3 years. Overall, 11.80% (813/6890) subjects developed NAFLD over 3 years of follow-up. The cumulative incidence of NAFLD increased with progressively higher baseline serum uric acid levels (the cumulative incidence was 7.2%, 9.5%, 11.5%, 13.8%, and 17.2% in quintile 1, quintile 2, 3, 4 and 5, respectively; P value for trend <0.001). Cox proportional hazards regression analyses showed that serum uric acid levels were independently and positively associated with the risk for incident NAFLD; the age-, gender- and metabolic syndrome adjusted hazard ratio (95% CI) for the subjects in quintile 2, 3, 4 and 5 versus quintile 1 was 1.18 (0.91–1.54), 1.32 (1.03–1.70), 1.39 (1.09–1.78) and 1.50 (1.18–1.92), respectively. Taken together, our prospective observational study showed that elevation of serum uric acid levels independently predicts increase risk for incident NAFLD