Objectives
Human age‐dependent telomere attrition and telomere shortening are associated with several age‐associated diseases and poorer overall survival. The aim of this study was to determine ...longitudinal leucocyte telomere length dynamics and identify factors associated with temporal changes in telomere length.
Design and Methods
Leucocyte telomere length was measured by quantitative polymerase chain reaction in 8074 participants from the Prevention of Renal and Vascular End‐stage Disease (PREVEND) study, an ongoing community‐based prospective cohort study initiated in 1997. Follow‐up data were available at two time‐points up to 2007. Leucocyte telomere length was measured, on between one and three separate occasions, in a total of 16 783 DNA samples. Multilevel growth models were created to identify the factors that influence leucocyte telomere dynamics.
Results
We observed an average attrition rate of 0.47 ± 0.16 relative telomere length units (RTLUs) per year in the study population aged 48 (range 39–60) years at baseline. Annual telomere attrition rate increased with age (P < 0.001) and was faster on average in men than in women (P for interaction 0.043). The major independent factors determining telomere attrition rate were active smoking (approximately tripled the loss of RTLU per year, P < 0.0001) and multiple traits of the metabolic syndrome (waist–hip ratio, P = 0.007; blood glucose level, P = 0.045, and HDL cholesterol level, P < 0.001).
Conclusions
Smoking and variables linked to the metabolic syndrome are modifiable lifestyle factors that accelerate telomere attrition in humans. The higher rate of cellular ageing may mediate the link between smoking and the metabolic syndrome to an increased risk of several age‐associated diseases.
Background: The objectives of this systematic review are to examine how researchers report missing data in questionnaires and to provide an overview of current methods for dealing with missing data. ...Methods: We included 262 studies published in 2010 in 3 leading epidemiologic journals. Information was extracted on how missing data were reported, types of missing, and methods for dealing with missing data. Results: Seventy-eight percent of the studies lacked clear information about the measurement instruments. Missing data in multi-item instruments were not handled differently from other missing data. Complete-case analysis was most frequently reported (81% of the studies), and the selectivity of missing data was seldom examined. Conclusions: Although there are specific methods for handling missing data in item scores and in total scores of multi-item instruments, these are seldom applied. Researchers mainly use complete-case analysis for both types of missing, which may seriously bias the study results.
. de Boer RA, van Veldhuisen DJ, Gansevoort RT, Muller Kobold AC, van Gilst WH, Hillege HL, Bakker SJL, van der Harst P (University of Groningen). The fibrosis marker galectin‐3 and outcome in the ...general population. J Intern Med 2012; 272: 55–64.
Objective. Galectin‐3 is involved in fibrosis and inflammation and plays a role in heart failure, renal disease, obesity and cancer. We aimed to establish the relationship between galectin‐3 and cardiovascular (CV) risk factors and mortality in the general population.
Design and subjects. This study included 7968 subjects from the Prevention of REnal and Vascular ENd‐stage Disease (PREVEND) cohort, with a median follow‐up of approximately 10 years. Plasma galectin‐3 was measured in baseline samples.
Main outcome measures. We investigated the relationships between galectin‐3 levels, demographic characteristics and risk factors of CV disease. We determined the prognostic value for all‐cause, CV and cancer mortality.
Results. The mean age of the population was 50 ± 13 years. Mean blood pressure was 129/74 mmHg, mean cholesterol was 5.7 ± 1.1 mmol L−1 and median galectin‐3 was 10.9 ng mL−1 interquartile range (IQR) 9.0–13.1. Galectin‐3 levels correlated with a wide range of risk factors of CV disease, including blood pressure, serum lipids, body mass index, renal function and N‐terminal pro‐B‐type natriuretic peptide (P < 0.0001). We observed a strong association between galectin‐3 and age. Furthermore, we found a gender interaction, with female subjects (n = 4001) having higher median galectin‐3 levels (11.0 ng mL−1, IQR 9.1–13.4 vs. men (n = 3967) 10.7 ng mL−1, IQR 8.9–12.8; P < 0.0001), and galectin‐3 levels in women more strongly correlated with risk factors of CV disease. After correction for the classical CV risk factors (smoking, blood pressure, cholesterol and diabetes), galectin‐3 levels independently predicted all‐cause mortality (hazard ratio per SD galectin‐3 1.09, 95% CI 1.01–1.19; P = 0.036), but not CV and cancer mortality separately.
Conclusions. Galectin‐3 is associated with age and risk factors of CV disease, with a strong gender interaction for these correlations. Galectin‐3 predicts all‐cause mortality in the general population.
Aim
The aim of this study was to investigate the differences in the performance and appreciation of students working in a virtual learning environment with two (2D)‐ or three (3D)‐dimensional vision.
...Material and methods
One hundred and twenty‐four randomly divided first‐year dental students performed a manual dexterity exercise on the Simodont dental trainer with an automatic assessment. Group 1 practised in 2D vision and Group 2 in 3D. All of the students practised five times for 45 min and then took a test using the vision they had practised in. After test 1, all of the students switched the type of vision to control for the learning curve: Group 1 practised in 3D and took a test in 3D, whilst Group 2 practised in 2D and took the test in 2D. To pass, three of five exercises had to be successfully completed within a time limit. The students filled out a questionnaire after completing test 2.
Results
The results show that students working with 3D vision achieved significantly better results than students who worked in 2D. Ninety‐five per cent of the students filled out the questionnaire, and over 90 per cent preferred 3D vision.
Conclusion
The use of 3D vision in a virtual learning environment has a significant positive effect on the performance of the students as well as on their appreciation of the environment.
The use of 3D FLAIR improves the detection of brain lesions in MS patients, but requires long acquisition times. Compressed sensing reduces acquisition time by using the sparsity of MR images to ...randomly undersample the k-space. Our aim was to compare the image quality and diagnostic performance of 3D-FLAIR with and without compressed sensing for the detection of multiple sclerosis lesions at 3T.
Twenty-three patients with relapsing-remitting MS underwent both conventional 3D-FLAIR and compressed sensing 3D-FLAIR on a 3T scanner (reduction in scan time 1 minute 25 seconds, 27%; compressed sensing factor of 1.3). Two blinded readers independently evaluated both conventional and compressed sensing FLAIR for image quality (SNR and contrast-to-noise ratio) and the number of MS lesions visible in the periventricular, intra-juxtacortical, infratentorial, and optic nerve regions. The volume of white matter lesions was measured with automatic postprocessing segmentation software for each FLAIR sequence.
Image quality and the number of MS lesions detected by the readers were similar between the 2 FLAIR acquisitions (
= .74 and
= .094, respectively). Almost perfect agreement was found between both FLAIR acquisitions for total MS lesion count (Lin concordance correlation coefficient = 0.99). Agreement between conventional and compressed sensing FLAIR was almost perfect for periventricular and infratentorial lesions and substantial for intrajuxtacortical and optic nerve lesions. Postprocessing with the segmentation software did not reveal a significant difference between conventional and compressed sensing FLAIR in total MS lesion volume (
= .63) or the number of MS lesions (
= .15).
With a compressed sensing factor of 1.3, 3D-FLAIR is 27% faster and preserves diagnostic performance for the detection of MS plaques at 3T.
The network approach to psychopathology conceives mental disorders as sets of symptoms causally impacting on each other. The strengths of the connections between symptoms are key elements in the ...description of those symptom networks. Typically, the connections are analysed as linear associations (i.e., correlations or regression coefficients). However, there is insufficient awareness of the fact that differences in variance may account for differences in connection strength. Differences in variance frequently occur when subgroups are based on skewed data. An illustrative example is a study published in PLoS One (2013;8(3):e59559) that aimed to test the hypothesis that the development of psychopathology through "staging" was characterized by increasing connection strength between mental states. Three mental states (negative affect, positive affect, and paranoia) were studied in severity subgroups of a general population sample. The connection strength was found to increase with increasing severity in six of nine models. However, the method used (linear mixed modelling) is not suitable for skewed data.
We reanalysed the data using inverse Gaussian generalized linear mixed modelling, a method suited for positively skewed data (such as symptoms in the general population).
The distribution of positive affect was normal, but the distributions of negative affect and paranoia were heavily skewed. The variance of the skewed variables increased with increasing severity. Reanalysis of the data did not confirm increasing connection strength, except for one of nine models.
Reanalysis of the data did not provide convincing evidence in support of staging as characterized by increasing connection strength between mental states. Network researchers should be aware that differences in connection strength between symptoms may be caused by differences in variances, in which case they should not be interpreted as differences in impact of one symptom on another symptom.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background and Purpose
Hypertension is an important mediator of cardiac damage and remodelling. Hydrogen sulfide (H2S) is an endogenously produced gasotransmitter with cardioprotective properties. ...However, it is not yet in clinical use. We, therefore, investigated the protective effects of sodium thiosulfate (STS), a clinically applicable H2S donor substance, in angiotensin II (Ang II)‐induced hypertensive cardiac disease in rats.
Experimental Approach
Male Sprague Dawley rats were infused with Ang II (435 ng kg min−1) or saline (control) for 3 weeks via s.c. placed osmotic minipumps. During these 3 weeks, rats received i.p. injections of either STS, NaHS or vehicle (0.9% NaCl).
Key Results
Compared with controls, Ang II infusion caused an increase in systolic and diastolic BP with associated cardiac damage as evidenced by cardiac hypertrophy, an increase in atrial natriuretic peptide (ANP) mRNA, cardiac fibrosis and increased oxidative stress. Treatment with NaHS and STS prevented the development of hypertension and the increase in ANP mRNA levels. Furthermore, the degree of cardiac hypertrophy, the extent of histological fibrosis in combination with the expression of profibrotic genes and the levels of oxidative stress were all significantly decreased.
Conclusions and Implications
Ang II‐induced hypertensive cardiac disease can be attenuated by treatment with STS and NaHS. Although BP regulation is the most plausible mechanism of cardiac protection, the antifibrotic and antioxidant properties of released sulfide may also contribute to their effects. Our data show that H2S might be a valuable addition to the already existing antihypertensive and cardioprotective therapies.
Linked Articles
This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue‐6
Magnetic refrigeration techniques based on the magnetocaloric effect (MCE) have recently been demonstrated as a promising alternative to conventional vapour-cycle refrigeration. In a material ...displaying the MCE, the alignment of randomly oriented magnetic moments by an external magnetic field results in heating. This heat can then be removed from the MCE material to the ambient atmosphere by heat transfer. If the magnetic field is subsequently turned off, the magnetic moments randomize again, which leads to cooling of the material below the ambient temperature. Here we report the discovery of a large magnetic entropy change in MnFeP0.45As0.55, a material that has a Curie temperature of about 300 K and which allows magnetic refrigeration at room temperature. The magnetic entropy changes reach values of 14.5 J K-1 kg-1 and 18 J K-1 kg-1 for field changes of 2 T and 5 T, respectively. The so-called giant-MCE material Gd5Ge2Si2 (ref. 2) displays similar entropy changes, but can only be used below room temperature. The refrigerant capacity of our material is also significantly greater than that of Gd (ref. 3). The large entropy change is attributed to a field-induced first-order phase transition enhancing the effect of the applied magnetic field.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cardiac stress can induce morphological, structural and functional changes of the heart, referred to as cardiac remodeling. Myocardial infarction or sustained overload as a result of pathological ...causes such as hypertension or valve insufficiency may result in progressive remodeling and finally lead to heart failure (HF). Whereas pathological and physiological (exercise, pregnancy) overload both stimulate cardiomyocyte growth (hypertrophy), only pathological remodeling is characterized by increased deposition of extracellular matrix proteins, termed fibrosis, and loss of cardiomyocytes by necrosis, apoptosis and/or phagocytosis. HF is strongly associated with age, and cardiomyocyte loss and fibrosis are typical signs of the aging heart. Fibrosis results in stiffening of the heart, conductivity problems and reduced oxygen diffusion, and is associated with diminished ventricular function and arrhythmias. As a consequence, the workload of cardiomyocytes in the fibrotic heart is further augmented, whereas the physiological environment is becoming less favorable. This causes additional cardiomyocyte death and replacement of lost cardiomyocytes by fibrotic material, generating a vicious cycle of further decline of cardiac function. Breaking this fibrosis-cell death axis could halt further pathological and age-related cardiac regression and potentially reverse remodeling. In this review, we will describe the interaction between cardiac fibrosis, cardiomyocyte hypertrophy and cell death, and discuss potential strategies for tackling progressive cardiac remodeling and HF.
As the heart matures during embryogenesis from its foetal stages, several structural and functional modifications take place to form the adult heart. This process of maturation is in large part due ...to an increased volume and work load of the heart to maintain proper circulation throughout the growing body. In recent years, it has been observed that these changes are reversed to some extent as a result of cardiac disease. The process by which this occurs has been characterized as cardiac foetal reprogramming and is defined as the suppression of adult and re‐activation of a foetal genes profile in the diseased myocardium. The reasons as to why this process occurs in the diseased myocardium are unknown; however, it has been suggested to be an adaptive process to counteract deleterious events taking place during cardiac remodelling. Although still in its infancy, several studies have demonstrated that targeting foetal reprogramming in heart failure can lead to substantial improvement in cardiac functionality. This is highlighted by a recent study which found that by modulating the expression of 5‐oxoprolinase (OPLAH, a novel cardiac foetal gene), cardiac function can be significantly improved in mice exposed to cardiac injury. Additionally, the utilization of angiotensin receptor neprilysin inhibitors (ARNI) has demonstrated clear benefits, providing important clinical proof that drugs that increase natriuretic peptide levels (part of the foetal gene programme) indeed improve heart failure outcomes. In this review, we will highlight the most important aspects of cardiac foetal reprogramming and will discuss whether this process is a cause or consequence of heart failure. Based on this, we will also explain how a deeper understanding of this process may result in the development of novel therapeutic strategies in heart failure.
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