Multimodal information improves the rapid detection of mental fatigue

One of the major challenge in the detection of mental states is improving the accuracy of brain activity-based detectors with additional information from extracranial signals. We assessed the suitability, for real-time mental fatigue detection, of EEG, EOG and ECG measurements, taken separately or together. Thirteen subjects performed six blocks of switching tasks. For each participant, the block with the lowest error rate from the first two blocks and the block with the highest error rate from the last three blocks were discriminated with a machine learning algorithm (support vector machine). The classification scores obtained with ECG or EOG were greater than would be expected by chance (>50%) for time windows of at least 8 s. EEG was the best single mode of detection, with classification scores ranging from 80 ± 3% with a 4 s time window to 94 ± 2% with a 30 s time window. The addition of ECG and EOG features to EEG features significantly increased classification scores for short time windows (e.g., to 86 ± 3% with a 4 s time window, p < 0.001). For short time windows (up to 12 s), ECG significantly increased the discriminatory power of EEG, whereas EOG did not. These results demonstrate that mental state detection on the basis of extracerebral measurements is feasible and that a combination of EEG and ECG is particularly appropriate for the rapid detection of mental fatigue.     

Estimating the cortex and autonomic nervous activity during a mental arithmetic task

The cerebral cortex has massive connections with autonomic nervous system and then arouses cardiovascular events, but the coupling mechanism between brain and heart is not clear. In this study the heart rate variability (HRV) and directed transfer function (DTF) methods are used to investigate the cortico-cortical functional coupling and direction of information flow between brain and heart during a mental arithmetic (MA) task. Electroencephalogram (EEG) and ECG were used for measuring neural/cardiac activity. Forty-three healthy male subjects were voluntarily participated in the study. Our results showed compared with control, LF/HF and LFn significantly increased while HF, HFn and total power significantly decreased (P < 0.05) during MA task. HR (79 ± 1.7 beats/min) was also significantly higher compared with the control (71 ± 1.4 beats/min). Moreover, MA task trigger the neurons of pre-central and central areas and then information transmit from front to back, and finished information integration at parietal and occipital locations. Our findings suggested that MA task caused an increase of the coupling of brain regions and quickened heart rate by virtue of increasing sympathetic activity and decreasing parasympathetic activity. The regulation from post-central areas to heart as well as feedback regulation from heart to central areas exists in the MA task.     

Prolonged cardioprotective effect of pyridostigmine encapsulated in liposomes

AimsThe purpose of the present work was to investigate the ability of pyridostigmine encapsulated in long-circulating liposomes, to protect against ECG (electrocardiogram) alterations induced by sympathetic stimulation in rats.Main methodsThe encapsulation of pyridostigmine was carried out by freeze–thaw and extrusion. Blood pressure and ECG (limb lead II) were monitored in anaesthetized male Wistar rats. The formulation containing pyridostigmine was intravenously administrated in 0.1, 0.3 and 1.0 mg/kg doses, and sympathetic stimulation was conducted by administration of 1 or 3 μg of noradrenaline (NA) after 1, 2, 4 or 6 h. The obtained cardiovascular parameters were compared to animals that received intravenous injection of pyridostigmine in free form or saline.Key findingsAfter saline, NA induced a significant increase in QT interval (22.3% after 3.0 μg). Previous administration of free pyridostigmine significantly prevented the increase of QT interval after sympathetic stimulation and the most prominent effect was observed after 1 h for the dose of 0.3 mg/kg (6.8% after 3.0 μg of NA) and was no longer observed after 2 h of the treatment. On the other hand, the maximum effect of pyridostigmine in liposomal formulation preventing QT interval increase was observed 2 h after treatment (9.7% after 3.0 μg of NA) and was still present until 6 h when 1 mg/kg was previous administrated.SignificanceThe results of the present study, beyond to confirm the cardioprotective action of pyridostigmine, suggest that liposomal pyridostigmine may be a potential therapeutic alternative to prevent cardiovascular disturbances resulting from sympathetic hyperactivity.     

The interpretation of abdominal wall muscle recruitment strategies change when the electrocardiogram (ECG) is removed from the electromyogram (EMG)

The purpose of this study was to determine the effect of the ECG artifact on low-level trunk muscle activation amplitudes and assess the effectiveness of two methods used to remove the ECG. Simulations were performed and percent error in root mean square (RMS) amplitudes were calculated from uncontaminated and contaminated EMG signals at various ECG to EMG ratios. Two methods were used to remove the ECG: (1) filtering by adaptive sampling (FAS) and (2) Butterworth high pass filter at 30 Hz (BW-30 Hz HPF). The percent error was also calculated between the ECG removed and the uncontaminated EMG RMS amplitudes. Next, the BW-30 Hz HPF method was used to remove the ECG from 3-bilateral external oblique (EO) muscle sites collected from 30 healthy subjects performing a one handed lift and replace task. Two separate ANOVA models assessed the effects of ECG on the statistical interpretation of EO recruitment strategies. One model included EMG data that contained the ECG and the other model included EMG data after the ECG was removed. Large percent errors were observed when the ECG was not removed. These errors increased with larger ECG to EMG ratios. Both removal methods reduced the errors to below 10%, but the BW-30 Hz HPF method was more time efficient in removing the ECG artifact. Different statistical findings were observed among the muscle sites for the ECG contaminated model compared to the ECG removed model, which resulted in different conclusions concerning neuromuscular control.     

Developmental variation of the blow fly Lucilia sericata (Meigen, 1826) (Diptera: Calliphoridae) by different substrate tissue types

The green bottle blow fly Lucilia sericata is recognized as being among the first wave of the faunal succession on human cadavers. Thus, it is used to estimate the postmortem interval (PMI). The nutritional intake of larvae is likely to vary subject to the part of a corpse on which they are feeding. A study was therefore conducted to investigate the effect for the type of food substrate on larval growth in this species. Larvae were reared on cow liver, brain, heart, lung, kidney, intestine or minced meat. Results showed significant differences in the duration of the feeding, postfeeding larval, and pupal stages from different substrata (F = 42.43; 74.71 and 655.71; P < 0.0001, respectively). Larval growth measured as length varied significantly between different tissues (F = 3.56; P < 0.05). Larvae that were reared on heart were smaller than those reared on other tissues. Also, there was a significant effect for the type of tissue on the adult size of males (F = 2.41, P < 0.05) and females (F = 2.85, P < 0.05). These results may have important implications for forensic entomologists, since initial infestations commonly occur in wounds or in the cranial area. Therefore, the position at which larvae have been feeding on a body will be a crucial observation at a crime scene and is very important in PMI estimation.     

Atrial flutter and atrial tachycardia detection using Bayesian approach with high resolution time–frequency spectrum from ECG recordings

Contemporary methods of atrial flutter (AFL), atrial tachycardia (AT), and atrial fibrillation (AF) monitoring, although superior to the standard 12-lead ECG and symptom-based monitoring, are unable to accurately discriminate between AF, AFL and AT. Thus, there is a need to develop accurate, automated, and comprehensive atrial arrhythmia detection algorithms using standard ECG recorders. To this end, we have developed a sensitive and real-time realizable algorithm for accurate AFL and AT detection using any standard electrocardiographic recording. Our novel method for automatic detection of atrial flutter and atrial tachycardia uses a Bayesian approach followed by a high resolution time–frequency spectrum. We find the TQ interval of the electrocardiogram (ECG) corresponding to atrial activity by using a particle filter (PF), and analyze the atrial activity with a high resolution time–frequency spectral method: variable frequency complex demodulation (VFCDM). The rationale for using a high-resolution time–frequency algorithm is that our approach tracks the time-varying fundamental frequency of atrial activity, where AT is within 2.0–4.0 Hz, AFL is within 4.0–5.3 Hz and NSR is found at frequencies less than 2.0 Hz. For classifications of AFL (n = 22), AT (n = 10) and normal sinus rhythms (NSR) (n = 29), we found that our approach resulted in accuracies of 0.89, 0.87 and 0.91, respectively; the overall accuracy was 0.88.     

Mitochondrial DNA haplogroup H as a risk factor for idiopathic dilated cardiomyopathy in Spanish population

Idiopathic dilated cardiomyopathy (IDC) is a structural heart disease with strong genetic background. The different single nucleotide polymorphisms (SNPs) that constitute mitochondrial haplogroups could play an important role in IDC progression. The aim of this study was to test frequencies of mitochondrial haplogroups in healthy controls (n = 422) and IDC patients (n = 304) of a Caucasian Spanish population. To achieve this, ten major European haplogroups were identified. Frequencies and Odds Ratios for the association between IDC and haplogroups were calculated in both groups. We found that compared to healthy controls, the prevalence of haplogroup H was significantly higher in IDC patients (40.0% vs 50.7%, p-value = 0.040).     

The effect of summation of contraction on acceleration signals in human skeletal muscle

The purpose of this study was to determine the effects of summation of contraction on acceleration signals in human skeletal muscle. The torque parameters of dorsiflexion and acceleration signals in the tibialis anterior muscle were measured during evoked isometric contractions. In an examination of two-pulse trains with different inter-pulse intervals, the torque and accelerometer responses to inter-pulse intervals of 10–100 ms were recorded. In an investigation of the effects of different numbers of stimuli, the torque and accelerometer responses to 1–8 pulses with a constant inter-pulse interval of 10 ms were recorded. The present study found that there was a difference in acceleration amplitude between the single-pulse and two-pulse trains with an inter-pulse interval of 10 ms but not two-pulse trains with an inter-pulse interval of 20 ms or more. In the investigation of different numbers of stimuli, we found a similar MMG amplitude across 2–8 pulses. Moreover, we observed that the maximal time to the peak acceleration signal was ～27 ms. In a comparison of torque parameters with acceleration signals, the present study clearly shows that acceleration amplitude is poorly correlated to changes in force parameters when the inter-pulse interval or the number of stimuli are increased. These results suggest that the absence of associated changes in acceleration peak is due to the long interval for the subsequent pulses relative to the time at which acceleration peak is achieved (～27 ms). These findings will provide useful information concerning the method for assessing summation of contraction with an accelerometer.     

A visual patient feedback device using optical surface measurement for the cooperative management of setup and body dynamics during radiotherapy

In this technical note we describe a real-time visual feedback device for use during radiotherapy treatment. The device displays a patient's live pose and position, relative to a reference, to them, helping them to control and maintain their motion. The device uses an optical sensor system developed at The Christie NHS Foundation Trust that is capable of real-time performance of up to 24 unique wide-area body surface measurements per second. The feedback device has integrated audio and three intuitive visualisation modes designed to show different levels of detail with varying degrees of complexity: a ‘2D traffic-light display’, ‘3D flexing lamina display’ and ‘3D colour-mapped surface display’. The performance characteristics of the system were measured, with the frame rate, throughput and latency of the feedback device being 22.4 fps, 47.0 Mbps, 109.8 ms, and 13.7 fps, 86.4 Mbps, 119.1 ms for single and three-channel modes respectively. We additionally present a novel fast method for calculating the vertical displacement map of two 3D surfaces suitable for live, real time display and evaluate its precision with respect to other methodologies.     

C-type natriuretic peptide plasma levels are reduced in obese adolescents

The high prevalence of obesity in children may increase the magnitude of lifetime risk of cardiovascular disease (CD). At present, explicit data for recommending biomarkers as routine pre-clinical markers of CD in children are lacking. C-type natriuretic peptide (CNP) is assuming increasing importance in CD; in adults with heart failure, its plasma levels are related to clinical and functional disease severity. We have previously reported five different reference intervals for blood CNP as a function of age in healthy children; however, data on plasma CNP levels in obese children are still lacking. Aim of this study was to assess CNP levels in obese adolescents and verify whether they differ from healthy subjects. Plasma CNP was measured in 29 obese adolescents (age: 11.8 ± 0.4 years; BMI: 29.8 ± 0.82) by radioimmunoassay and compared with the reference values of healthy subjects. BNP was also measured. Both plasma CNP and BNP levels were significantly lower in the obese adolescents compared to the appropriate reference values (CNP: 3.4 ± 0.2 vs 13.6 ± 2.3 pg/ml, p < 0.0001; BNP: 18.8 ± 2.6 vs 36.9 ± 5.5 pg/ml, p = 0.003). There was no significant difference between CNP values in males and females. As reported in adults, we observed lower plasma CNP and BNP levels in obese children, suggesting a defective natriuretic peptide system in these patients. An altered regulation of production, clearance and function of natriuretic peptides, already operating in obese adolescents, may possibly contribute to the future development of CD. Thus, the availability of drugs promoting the action of natriuretic peptides may represent an attractive therapeutic option to prevent CD.     

Effect of electrocardiographic contamination on surface electromyography assessment of back muscles

The purpose of this study was to demonstrate the relative effect of electrocardiography (ECG) on back muscle surface electromyography (SEMG) parameters and their corresponding sensitivity in low back pain (LBP) assessment.Back muscle SEMG activities were recorded from 17 healthy subjects and 18 chronic LBP patients under static postures (straight sitting and upright standing), and dynamic action (flexion–extension). ECG cancellation based on independent component analysis (ICA) method was performed. Root mean square (RMS) and median frequency (MF) of raw and denoised SEMG data were computed respectively. Multiple comparisons were then performed.A consistent trend of change (increased MF and decreased RMS) followed ECG removal was noticed. In particular, in SEMG measurements under static postures, a significant decrease in RMS (p < 0.05) and increase in MF (p < 0.05) were found in all recording muscle groups. Level of corruption by ECG artifacts on SEMG measurements was found to be more serious and prominent in static postures than that in dynamic action. After ECG removal, significant improvements in the ability of SEMG to discriminate LBP patients from healthy subjects were seen in RMS amplitude recorded while standing (p < 0.05) and MF in all measuring conditions (p < 0.05).This study provides a more complete understanding on the relative effect of ECG contamination on back muscles SEMG parameters and LBP assessment.     

Pretreatment with a combination of quercetin and α-tocopherol ameliorates adenosine triphosphatases and lysosomal enzymes in myocardial infarcted rats

AimsMembrane bound adenosine triphosphatases (ATPases) and lysosomal enzymes play an important role in the pathology of myocardial infarction. This study was aimed to evaluate the combined preventive effects of quercetin and α-tocopherol on membrane bound ATPases and lysosomal enzymes in isoproterenol induced myocardial infarcted rats.Main methodsMale Wistar rats were pretreated with a combination of quercetin (10 mg/kg) and α-tocopherol (10 mg/kg) daily for 14 days. After the pretreatment period, isoproterenol (100 mg/kg) was injected to rats at an interval of 24 h for two days to induce myocardial infarction. The activities of ATPases and lysosomal enzymes were assayed.Key findingsIsoproterenol treated rats showed decreased levels of heart creatine kinase and lactate dehydrogenase. The activity of sodium potassium adenosine triphosphatase was decreased and the activities of magnesium adenosine triphosphatase and calcium adenosine triphosphatase were increased in isoproterenol treated rats. Also, the activities of β-glucuronidase, β-N-acetylglucosaminidase, β-galactosidase, cathepsin-B and D were increased (serum and heart), but the activities of β-glucuronidase and cathepsin-D were decreased in lysosomal fraction and increased in cytosolic fraction of the heart in isoproterenol treated rats. Furthermore, the heart lipid peroxidation products were increased in isoproterenol treated rats. Combined pretreatment with quercetin and α-tocopherol to isoproterenol treated rats normalized all the biochemical parameters studied. The observed effects are due to their membrane stabilizing property and this property might be due to decreased lipid peroxidation.SignificanceOur study demonstrated that combined pretreatment was better than single pretreatment. This study may have significant impact on myocardial infarcted patients.     

Choice of scan-sampling intervals—An example with quantifying neighbours in dairy cows

To date, only a few studies using scan-sampling intervals to record neighbours in groups of animals explain how the interval length was chosen. In this study, we investigated the effects of different scan-sampling intervals, behavioural context, and the definition of neighbours on the accuracy of data as compared to a quasi-continuous observation. The data was collected from dairy cows kept in cubicle housing systems. Dairy herds of 22–43 cows on 6 farms were observed once a minute with an automatic tracking system for 6 days, and both the nearest neighbour and all neighbours within a defined distance of each cow were recorded with references to the activity, feeding and lying area and stored in neighbourship matrices. In the analysis, we used data collected at intervals of 2, 3, 4, …, 30 min, and correlated this simulated data with the data based on the 1-min interval using a specialised correlation coefficient for matrices τ_Kr. This correlation coefficient was then used as the response variable in mixed-effects models. We found that the size of the correlation coefficients generally decreased as interval length increased. This decrease was less pronounced for all neighbours than for the nearest neighbour. Moreover, the decrease was greatest with data from the activity area and lowest with data from the lying area. We concluded that, even with the relatively slow dairy cows in a barn environment, neighbour recordings should be conducted at short scan-sampling intervals in order to achieve a minimum correlation of τ_Kr = 0.8 with the quasi-continuous data. Intervals of every 2, 8 and 17 min are recommended for observation of neighbours in dairy cows for the activity, feeding and lying areas, respectively, and species that move faster may well require even shorter sampling intervals.     

Pharmacological evaluation of R(+)-pulegone on cardiac excitability: Role of potassium current blockage and control of action potential waveform

IntroductionR(+)-pulegone is a ketone monoterpene and it is the main constituent of essential oils in several plants. Previous studies provided some evidence that R(+)-pulegone may act on isolated cardiac myocytes. In this study, we evaluated in extended detail, the pharmacological effects of R(+)-pulegone on cardiac tissue.MethodsUsing in vivo measurements of rat cardiac electrocardiogram (ECG) and patch-clamp technique in isolated myocytes we determinate the influence of R(+)-pulegone on cardiac excitability.ResultsR(+)-pulegone delayed action potential repolarization (APR) in a concentration-dependent manner (EC₅₀ = 775.7 ± 1.48, 325.0 ± 1.30, 469.3 ± 1.91 μM at 10, 50 and 90% of APR respectively). In line with prolongation of APR R(+)-pulegone, in a concentration-dependent manner, blocked distinct potassium current components (transient outward potassium current (I_to), rapid delayed rectifier potassium current (I_Kr), inactivating steady state potassium current (I_ss) and inward rectifier potassium current (I_K1)) (EC₅₀ = 1441 ± 1.04; 605.0 ± 1.22, 818.7 ± 1.22; 1753 ± 1.09 μM for I_to, I_Kr, I_ss and I_K1, respectively). The inhibition occurred in a fast and reversible way, without changing the steady-state activation curve, but instead shifting to the left the steady-state inactivation curve (V_1/2 from −56.92 ± 0.35 to −67.52 ± 0.19 mV). In vivo infusion of 100 mg/kg R(+)-pulegone prolonged the QTc (∼40%) and PR (∼62%) interval along with reducing the heart rate by ∼26%.ConclusionTaken together, R(+)-pulegone prolongs the APR by inhibiting several cardiomyocyte K⁺ current components in a concentration-dependent manner. This occurs through a direct block by R(+)-pulegone of the channel pore, followed by a left shift on the steady state inactivation curve. Finally, R(+)-pulegone induced changes in some aspects of the ECG profile, which are in agreement with its effects on potassium channels of isolated cardiomyocytes.     

Uncertainty in detecting the disturbance history of forest ecosystems using dendrochronology

QuestionsUncertainty in detecting disturbance histories has long been ignored in dendrochronological studies in forest ecosystems. Our goal was to characterize this uncertainty in relation to the key parameters of forest ecosystems and sample size. In addition, we aimed to provide a method to define uncertainty bounds in specific forest ecosystems with known parameters, and to provide a required (conservative) minimal sample size to achieve a pre-defined level of uncertainty if no actual key forest parameters are known.LocationTraining data were collected from Žofínský Prales (48°40′N, 14°42′E, 735–830 m a.s.l., granite, Czech Republic).MethodsWe used probability theory and expressed uncertainty as the length (the difference between the upper and lower bounds) of the 95% confidence interval. We studied the uncertainty of (i) the initial growth of trees – if they originated under canopy or in a gap; and (ii) the responses to disturbance events during subsequent growth – on the basis of release detection in the radial growth of trees. These two variables provide different information, which together give a picture of the disturbance history. While initial growth date the existence of a gap in a given decade (recent as well as older gaps are included), release demonstrates the moment of a disturbance event.ResultsWith the help of general mathematical deduction, we have obtained results valid across vegetation types. The length of a confidence interval depends on the sample size, proportion of released trees in a population, as well as on the variability of tree layer features (e.g., crown area of suppressed and released trees).ConclusionsMost studies to date have evaluated the initial growth of trees with higher uncertainty than for canopy disturbed area. The length of the 95% confidence interval for detecting initial growth has been rarely shorter than 0.1 (error ± 5%) and has mostly been much longer. To reach 95% confidence interval length of 0.1 (error ± 5%) when detecting the canopy disturbed area, at least 485 tree cores should be evaluated in studied time period, while to reach a 0.05 interval length (error ± 2.5%) at least 1925 tree cores are required. Our approach can be used to find the required sample size in each specific forest ecosystem to achieve pre-defined levels of uncertainty while detecting disturbance history.     

2D and 3D CT Radiomics Features Prognostic Performance Comparison in Non-Small Cell Lung Cancer

OBJECTIVE: To compare 2D and 3D radiomics features prognostic performance differences in CT images of non-small cell lung cancer (NSCLC). METHOD: We enrolled 588 NSCLC patients from three independent cohorts. Two sets of 463 patients from two different institutes were used as the training cohort. The remaining cohort with 125 patients was set as the validation cohort. A total of 1014 radiomics features (507 2D features and 507 3D features correspondingly) were assessed. Based on the dichotomized survival data, 2D and 3D radiomics indicators were calculated for each patient by trained classifiers. We used the area under the receiver operating characteristic curve (AUC) to assess the prediction performance of trained classifiers (the support vector machine and logistic regression). Kaplan–Meier and Cox hazard survival analyses were also employed. Harrell's concordance index (C-Index) and Akaike's information criteria (AIC) were applied to assess the trained models. RESULTS: Radiomics indicators were built and compared by AUCs. In the training cohort, 2D_AUC = 0.653, 3D_AUC = 0.671. In the validation cohort, 2D_AUC = 0.755, 3D_AUC = 0.663. Both 2D and 3D trained indicators achieved significant results (P < .05) in the Kaplan-Meier analysis and Cox regression. In the validation cohort, 2D Cox model had a C-Index = 0.683 and AIC = 789.047; 3D Cox model obtained a C-Index = 0.632 and AIC = 799.409. CONCLUSION: Both 2D and 3D CT radiomics features have a certain prognostic ability in NSCLC, but 2D features showed better performance in our tests. Considering the cost of the radiomics features calculation, 2D features are more recommended for use in the current study.     

Plasma intermedin levels in patients with acute myocardial infarction

It has been shown that adrenomedullin (ADM) may function as a cardiovascular-regulatory peptide in humans. Intermedin (IMD) is a newly discovered peptide related to ADM and has a greater range of biological effects on the cardiovascular in animal experiments. The purpose of the study was to investigate the pathophysiological role of IMD in patients with acute myocardial infarction (AMI). The present study included twenty patients with acute ST-segment elevation myocardial infarction (STEMI), thirty-three with stable coronary heart disease (SCHD), and eighteen healthy controls. Plasma levels of IMD, malonaldehyde (MDA), and superoxide dismutase (SOD) and cardiac biomarkers were determined at one, two, four and seven days following AMI. Plasma IMD levels were significantly increased on day 1 in AMI patients when compared with SCHD subjects (P = 0.014), and reached a peak of 181.88 ± 9.47 pg/ml at 96 h. Plasma IMD concentrations were correlated with MDA and SOD. Furthermore, patients with severe lesions in their coronary arteries tended to have higher plasma IMD levels (P < 0.05) in AMI patients. A significant increase in plasma IMD following AMI may be associated with oxidative stress, and could be used as a marker to reflect the severity of the coronary stenosis.     

Prognostic value of circulating levels of stem cell growth factor beta (SCGF beta) in patients with Chagas’ disease and idiopathic dilated cardiomyopathy

Chagas’ disease (CD) often leads to dilated cardiomyopathy (DCM), and during its chronic stage hematopoietic stem or progenitor cells are involved in its pathological process. However, it is not clear whether stem cell growth factor (SCGF) beta can be regulated in patients with CD and idiopathic DCM. In present study, we aim to investigate the plasma SCGF beta concentration and its correlation with echocardiographic parameters and clinical outcome.In this prospective cohort study, SCGF beta levels were quantified in patients with CD (n = 94), DCM (n = 48), and control healthy subjects (n = 25). In comparison with healthy subjects, no statistical difference can be detected in NYHA classes I–II patients. However, SCGF beta was significantly increased in advanced heart failure patients (NYHA III–IV), compared to CD patients without heart failure. There was no group difference between CD and DCM. However, despite this significant increase in advanced heart failure patients, SCGF beta had no significant correlation with echocardiographic parameters, and it cannot be used as a prognostic marker for mortality and heart transplantation.To our best knowledge, this is the first report of SCGF beta in heart failure patients. Although it is significantly increased in advanced heart failure patients caused by CD or DCM, its prognostic value for end points is minor.     

Indoxyl sulfate promotes cardiac fibrosis with enhanced oxidative stress in hypertensive rats

AimsCardiovascular disease (CVD) is common in chronic kidney disease (CKD) patients. Indoxyl sulfate (IS) is a nephrovascular uremic toxin that induces oxidative stress in kidney and vascular system. The present study aimed to examine the effect of IS on fibrosis and oxidative stress in rat heart.Main methodsThe effects of IS on heart were examined by Masson's trichrome (MT) staining and immunohistochemistry using: (1) Dahl salt-resistant normotensive rats (DN), (2) Dahl salt-resistant normotensive IS-administered rats (DN + IS), (3) Dahl salt-sensitive hypertensive rats (DH), and (4) Dahl salt-sensitive hypertensive IS-administered rats (DH + IS).Key findingsDH + IS rats showed significantly increased heart weight and left ventricle weight compared with DN. DH and DH + IS rats showed significantly increased diameter of cardiomyocytes, increased MT-positive fibrotic area, increased staining for transforming growth factor (TGF)-β1, α-smooth muscle actin (SMA), type 1 collagen, NADPH oxidase Nox 4, malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG) and decreased staining for nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1 (HO-1) in the heart compared with DN. More notably, DH + IS rats showed significantly increased diameter of cardiomyocytes, increased fibrotic area, increased staining for TGF-β1, SMA, type 1 collagen, Nox4, 8-OHdG and MDA, and decreased staining for Nrf2 and HO-1 in the heart compared with DH.SignificanceIS aggravates cardiac fibrosis and cardiomyocyte hypertrophy with enhanced oxidative stress and reduced anti-oxidative defense in hypertensive rats.