Heart failure is a complex progressive clinical syndrome which is initiated by risk factors (e.g., hypertension, obesity, and diabetes), then proceeds to asymptomatic maladaptive left ventricular ...remodeling and dysfunction, and finally evolves into clinically overt, symptomatic heart failure, disability, and death. The progression of left ventricular dysfunction is associated with changes in cardiac energy metabolism. Mitochondria play a central role in a variety of cardiomyocytes functions, including oxidative energy production, storage of calcium ions, and programmed cell death. The mitochondrial DNA (mtDNA) content correlates with the size and number of mitochondria, which change under different energy demands and oxidative stress. Experimental studies demonstrated that any genetic manipulation resulting in significantly decreased mtDNA could accelerate the ageing process and cause adverse myocardial remodeling and dysfunction. On the other hand, preservation of the mtDNA copy number in mouse hearts delays the development of heart failure after myocardial infarction. Recent general population study also demonstrated that echocardiographic indexes of left ventricular structure and function are significantly and independently associated with mtDNA content measured at peripheral blood cells in cross-sectional and longitudinal analyses. In this chapter, we will discuss the recent experimental, clinical and epidemiological data of the possible impact of mtDNA content on cardiac structure and function.
In this work, dynamic mechanical contact behaviors and sintering mechanism of Al nanoparticles subjected to high-speed impact have been investigated using molecular dynamic simulations by analyzing ...radial distribution function (RDF), atomic average displacement, mean square displacement (MSD), the sintering neck radius, shrinkage, nanoparticle temperature and the proportion of amorphous atoms. The results shows that the long-ranged ordered structure of Al nanoparticles gradually transforms into short-range ordered structure and finally amorphous structure during the head-on impact. The atomic average displacement, MSD, radius ratio (x/R) and shrinkage at different initial impact speeds first experience a rapid increase to a maximum, followed by a slow decrease and subsequent a recovery to an almost constant. The displacement of surface atoms is always larger than the internal atoms during the head-on impact. There exists one critical impact velocity (e.g., 2800 m/s for given 4 nm in diameter) beyond which the ordered aluminum atoms completely transform into amorphous structure. The contact force, contact radius and contact stress obtained under a given low impact velocity and small strain are quite consistent with the predictions of the continuous Hertz model, but as the impact velocity and normal displacement further increase, the predictions of Hertz model underestimate these contact parameters. The influence of nanoparticle size on the relationship of contact radius and number of contacting atoms is inappreciable. The nanoparticles undergo elastic deformation, and then plastic deformation, followed by mechanical failure and shock-induced melting process into a whole. This work could strengthen our understanding of the industrial processes with applications in energetic nanomaterials, rocket propellant, metal sintering, etc.
•Contact behaviors and sintering mechanism of Al nanoparticles under impact have been studied by MD simulations.•The crystal structure of Al nanoparticles is continuously destroyed under high-speed impact.•Al nanoparticles with 4 nm in diameter will be melted when the initial impact velocity is greater than 2800 m/s.•Al nanoparticles have been undergone elastic and plastic deformation, mechanical failure and final melting.•The simulation results confirm that the Hertz model still hold only at low impact speed and at small strain.
The article discusses the issue of extensive use of detergents and sanitizers in the time of new challenges associated with the COVID-19 (SARS-CoV-2) pandemic. These agents could pose threats to the ...existence of free-living invertebrates as essential components of the ecosystem. The biological effects of the mentioned classes of substances, their metabolites, and combined effects in the mixture have not been studied enough. The main challenges in trying to balance the threats and benefits of using such substances are the lack of knowledge of the biological effects of these products, the gaps in testing invertebrates’ responses, and changes in environment-related regulations to minimize risks to animals and humans. Numerous studies in this field still leave research gaps, particularly concerning the combined toxicity of well-known and widely used disinfectants, surfactants, and heavy metals, posing potential future challenges. Additionally, the review identified the need for additional testing of invertebrates for their sensitivity to disinfectants and surfactants of different compositions, including improved (non-invasive) methods, studies for early life stages, and comparative studies of species resilience.
Small RNA molecules, called microRNAs, freely circulate in human plasma and correlate with varying pathologies. In this study, we explored their diagnostic potential in a selection of prevalent ...cardiovascular disorders.
MicroRNAs were isolated from plasmas from well-characterized patients with varying degrees of cardiac damage: (1) acute myocardial infarction, (2) viral myocarditis, (3) diastolic dysfunction, and (4) acute heart failure. Plasma levels of selected microRNAs, including heart-associated (miR-1, -133a, -208b, and -499), fibrosis-associated (miR-21 and miR-29b), and leukocyte-associated (miR-146, -155, and -223) candidates, were subsequently assessed using real-time polymerase chain reaction. Strikingly, in plasma from acute myocardial infarction patients, cardiac myocyte-associated miR-208b and -499 were highly elevated, 1600-fold (P<0.005) and 100-fold (P<0.0005), respectively, as compared with control subjects. Receiver operating characteristic curve analysis revealed an area under the curve of 0.94 (P<10(-10)) for miR-208b and 0.92 (P<10(-9)) for miR-499. Both microRNAs correlated with plasma troponin T, indicating release of microRNAs from injured cardiomyocytes. In viral myocarditis, we observed a milder but significant elevation of these microRNAs, 30-fold and 6-fold, respectively. Plasma levels of leukocyte-expressed microRNAs were not significantly increased in acute myocardial infarction or viral myocarditis patients, despite elevated white blood cell counts. In patients with acute heart failure, only miR-499 was significantly elevated (2-fold), whereas no significant changes in microRNAs studied could be observed in diastolic dysfunction. Remarkably, plasma microRNA levels were not affected by a wide range of clinical confounders, including age, sex, body mass index, kidney function, systolic blood pressure, and white blood cell count.
Cardiac damage initiates the detectable release of cardiomyocyte-specific microRNAs-208b and -499 into the circulation.
Progressive CKD is generally detected at a late stage by a sustained decline in eGFR and/or the presence of significant albuminuria. With the aim of early and improved risk stratification of patients ...with CKD, we studied urinary peptides in a large cross-sectional multicenter cohort of 1990 individuals, including 522 with follow-up data, using proteome analysis. We validated that a previously established multipeptide urinary biomarker classifier performed significantly better in detecting and predicting progression of CKD than the current clinical standard, urinary albumin. The classifier was also more sensitive for identifying patients with rapidly progressing CKD. Compared with the combination of baseline eGFR and albuminuria (area under the curve AUC=0.758), the addition of the multipeptide biomarker classifier significantly improved CKD risk prediction (AUC=0.831) as assessed by the net reclassification index (0.303±-0.065; P<0.001) and integrated discrimination improvement (0.058±0.014; P<0.001). Correlation of individual urinary peptides with CKD stage and progression showed that the peptides that associated with CKD, irrespective of CKD stage or CKD progression, were either fragments of the major circulating proteins, suggesting failure of the glomerular filtration barrier sieving properties, or different collagen fragments, suggesting accumulation of intrarenal extracellular matrix. Furthermore, protein fragments associated with progression of CKD originated mostly from proteins related to inflammation and tissue repair. Results of this study suggest that urinary proteome analysis might significantly improve the current state of the art of CKD detection and outcome prediction and that identification of the urinary peptides allows insight into various ongoing pathophysiologic processes in CKD.
Accumulation of mitochondrial DNA (mtDNA) mutations leads to alterations of mitochondrial biogenesis and function that might produce a decrease in mtDNA content within cells. This implies that mtDNA ...content might be a potential biomarker associated with oxidative stress and inflammation. However, data on correlates of mtDNA content in a general population are sparse. Our goal in the present study was to describe in a randomly recruited population sample the distribution and determinants of peripheral blood mtDNA content. From 2009 to 2013, we examined 689 persons (50.4% women; mean age = 54.4 years) randomly selected from a Flemish population (Flemish Study on Environment, Genes, and Health Outcomes). Relative mtDNA copy number as compared with nuclear DNA was measured by quantitative real-time polymerase chain reaction in peripheral blood. There was a curvilinear relationship between relative mtDNA copy number and age. mtDNA content slightly increased until the fifth decade of life and declined in older subjects (Page (2) = 0.0002). mtDNA content was significantly higher in women (P = 0.007) and increased with platelet count (P < 0.0001), whereas it was inversely associated with white blood cell count (P < 0.0001). We also observed lower mtDNA content in women using estroprogestogens (P = 0.044). This study demonstrated in a general population that peripheral blood mtDNA content is significantly associated with sex and age. Blood mtDNA content is also influenced by platelet and white blood cell counts and estroprogestogen intake. Further studies are required to clarify the impact of chronic inflammation and hormone therapy on mitochondrial function.
Hypertension in children and adolescents has gained ground in cardiovascular medicine, thanks to the progress made in several areas of pathophysiological and clinical research. These guidelines ...represent a consensus among specialists involved in the detection and control of high blood pressure in children and adolescents. The guidelines synthesize a considerable amount of scientific data and clinical experience and represent best clinical wisdom upon which physicians, nurses and families should base their decisions. They call attention to the burden of hypertension in children and adolescents, and its contribution to the current epidemic of cardiovascular disease, these guidelines should encourage public policy makers, to develop a global effort to improve identification and treatment of high blood pressure among children and adolescents.
A single-tier immunoassay using the C6 peptide of VlsE (C6) from Borrelia burgdorferi sensu stricto (Bb) has been proposed as a potential alternative to conventional two-tier testing for the ...serologic diagnosis of Lyme disease in the United States and Europe.
To evaluate the performance of C6 peptide based multiplex Phosphorescence Analysis (PHOSPHAN) for the serologic confirmation of Lyme borreliosis (LB) in Russian patients.
Serum samples (n = 351) were collected from 146 patients with erythema migrans (EM); samples from 131 of these patients were taken several times prior to treatment and at different stages of recovery. The control group consisted of 197 healthy blood donors and 31 patients with other diseases, all from the same highly endemic region of Russia. All samples were analyzed by PHOSPHAN for IgM and IgG to Bb C6, recombinant OspC and VlsE proteins, and C6 peptides from B. garinii and B. afzelii.
IgM and IgG to Bb C6 were identified in 43 and 95 out of 131 patients (32.8 and 72.5%, respectively); seroconversion of IgM antibodies was observed in about half of the patients (51.2%), and of IgG antibodies, in almost all of them (88.4%). Additional detection of OspC-IgM and VlsE-IgM or IgG to C6 from B. garinii or B. afzelii did not contribute significantly to the overall sensitivity of the multiplex immunoassay.
The multiplex phosphorescence immunoassay is a promising method for simultaneously revealing the spectrum of antibodies to several Borrelia antigens. Detection of IgM and IgG to Bb C6 in the sera of EM patients provides effective serologic confirmation of LB and, with high probability, indicates an active infection process.
The Cardiovascular Risk of White-Coat Hypertension Franklin, Stanley S., MD; Thijs, Lutgarde, MSc; Asayama, Kei, MD, PhD ...
Journal of the American College of Cardiology,
11/2016, Letnik:
68, Številka:
19
Journal Article
Recenzirano
Odprti dostop
Abstract Background The role of white-coat hypertension (WCH) and the white-coat-effect (WCE) in development of cardiovascular disease (CVD) risk remains poorly understood. Objectives Using data from ...the population-based, 11-cohort IDACO (International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular Outcomes), this study compared daytime ambulatory blood pressure monitoring with conventional blood pressure measurements in 653 untreated subjects with WCH and 653 normotensive control subjects. Methods European Society Hypertension guidelines were used as a 5-stage risk score. Low risk was defined as 0 to 2 risk factors, and high risk was defined as ≥3 to 5 risk factors, diabetes, and/or history of prior CVD events. Age- and cohort-matching was done between 653 untreated subjects with WCH and 653 normotensive control subjects. Results In a stepwise linear regression model, systolic WCE increased by 3.8 mm Hg (95% confidence interval CI: 3.1 to 4.6 mm Hg) per 10-year increase in age, and was similar in low- and high-risk subjects with or without prior CVD events. Over a median 10.6-year follow-up, incidence of new CVD events was higher in 159 high-risk subjects with WCH compared with 159 cohort- and age-matched high-risk normotensive subjects (adjusted hazard ratio HR: 2.06; 95% CI: 1.10 to 3.84; p = 0.023). The HR was not significant for 494 participants with low-risk WCH and age-matched low-risk normotensive subjects. Subgroup analysis by age showed that an association between WCH and incident CVD events is limited to older (age ≥60 years) high-risk WCH subjects; the adjusted HR was 2.19 (95% CI: 1.09 to 4.37; p = 0.027) in the older high-risk group and 0.88 (95% CI: 0.51 to 1.53; p = 0.66) in the older low-risk group (p for interaction = 0.044). Conclusions WCE size is related to aging, not to CVD risk. CVD risk in most persons with WCH is comparable to age- and risk-adjusted normotensive control subjects.
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