Heart rate differences between symptomatic and asymptomatic Brugada syndrome patients at night.

OBJECTIVE: Ventricular arrhythmias in Brugada syndrome (BS) mainly occur at rest, especially during nighttime, suggesting that parasympathetic activity at night may play an important role in the arrhythmogenesis of the disease. This study examined and compared the autonomic function of symptomatic and asymptomatic BS patients overnight. APPROACH: We analyzed various heart rate variability (HRV) and heart rate complexity (HRC) markers in a clinical series including 87 BS patients, where 23 were symptomatic. MAIN RESULTS: Statistically significant differences were found in markers MIRR, SDNN, SDANN, [Formula: see text] and SampEn, suggesting that symptomatic patients may be related to lower heart rate variability and complexity values, as well as to greater circadian fluctuations overnight. SIGNIFICANCE: The results provide further evidence for the role of autonomic imbalance in the pathophysiology of BS, highlighting the relevance of nighttime analysis to the unmasking of significant ANS changes. Based on these outcomes, the role of HRV and HRC assessment at night could be a step forward towards the understanding of BS and the risk for the occurrence of symptoms in these patients, with a potential future impact on therapeutic strategies.

Demonstration of Single-Barium-Ion Sensitivity for Neutrinoless Double-Beta Decay Using Single-Molecule Fluorescence Imaging.

A new method to tag the barium daughter in the double-beta decay of ^{136}Xe is reported. Using the technique of single molecule fluorescent imaging (SMFI), individual barium dication (Ba^{++}) resolution at a transparent scanning surface is demonstrated. A single-step photobleach confirms the single ion interpretation. Individual ions are localized with superresolution (∼2 nm), and detected with a statistical significance of 12.9σ over backgrounds. This lays the foundation for a new and potentially background-free neutrinoless double-beta decay technology, based on SMFI coupled to high pressure xenon gas time projection chambers.

Rheological Flow Behavior of Structural Polysaccharides from Edible Tender Cladodes of Wild, Semidomesticated and Cultivated 'Nopal' (Opuntia) of Mexican Highlands.

The aim of this study was to quantify the content of polysaccharides of edible tender cladodes (nopalitos) of three species of Opuntia and to evaluate the rheological flow behavior of isolated polysaccharides. A completely randomized experimental design was used to characterize a wild (O. streptacantha), a semidomesticated (O. megacantha) and a domesticated (O. ficus-indica) species. Mucilage content was higher (4.93 to 12.43 g 100 g-1 dry matter), tightly bound hemicelluloses were lower (3.32 to 1.81 g 100 g-1 dry matter) and pectins and loosely bound hemicelluloses were not different in wild than in domesticated species. Aqueous solution/suspensions of mucilage, pectins, hemicellulose and cellulose of all species showed non-Newtonian behavior under simple shear flow. The flow behavior of the structural polysaccharides was well described by the Ostwald de-Waele model. Pectins and mucilages exhibited the highest consistency indexes (K values ranged from 0.075 to 0.177 Pasn) with a moderated shear-thinning behavior (n values ranged from 0.53 to 0.67). Cellulose dispersions exhibited the most shear-thinning behavior (n values ranged from 0.17 to 0.41) and hemicelluloses showed a tendency to Newtonian flow (n values ranged from 0.82 to 0.97). The rheological flow properties of these polysaccharides may be useful to improve the textural and sensory qualities of some foods and pharmaceutical materials. Moreover, they can emerge as functional ingredients mainly due to the nutraceutical properties that have been attributed to nopalitos.

Coupled Hidden Markov Model-Based Method for Apnea Bradycardia Detection.

In this paper, we present a novel framework for the coupled hidden Markov model (CHMM), based on the forward and backward recursions and conditional probabilities, given a multidimensional observation. In the proposed framework, the interdependencies of states networks are modeled with Markovian-like transition laws that influence the evolution of hidden states in all channels. Moreover, an offline inference approach by maximum likelihood estimation is proposed for the learning procedure of model parameters. To evaluate its performance, we first apply the CHMM model to classify and detect disturbances using synthetic data generated by the FitzHugh-Nagumo model. The average sensitivity and specificity of the classification are above 93.98% and 95.38% and those of the detection reach 94.49% and 99.34%, respectively. The method is also evaluated using a clinical database composed of annotated physiological signal recordings of neonates suffering from apnea-bradycardia. Different combinations of beat-to-beat features extracted from electrocardiographic signals constitute the multidimensional observations for which the proposed CHMM model is applied, to detect each apnea bradycardia episode. The proposed approach is finally compared to other previously proposed HMM-based detection methods. Our CHMM provides the best performance on this clinical database, presenting an average sensitivity of 95.74% and specificity of 91.88% while it reduces the detection delay by -0.59 s.

Optimal algorithm switching for the estimation of systole period from cardiac microacceleration signals (SonR).

Previous studies have shown that cardiac microacceleration signals, recorded either cutaneously, or embedded into the tip of an endocardial pacing lead, provide meaningful information to characterize the cardiac mechanical function. This information may be useful to personalize and optimize the cardiac resynchronization therapy, delivered by a biventricular pacemaker, for patients suffering from chronic heart failure (HF). This paper focuses on the improvement of a previously proposed method for the estimation of the systole period from a signal acquired with a cardiac microaccelerometer (SonR sensor, Sorin CRM SAS, France). We propose an optimal algorithm switching approach, to dynamically select the best configuration of the estimation method, as a function of different control variables, such as the signal-to-noise ratio or heart rate. This method was evaluated on a database containing recordings from 31 patients suffering from chronic HF and implanted with a biventricular pacemaker, for which various cardiac pacing configurations were tested. Ultrasound measurements of the systole period were used as a reference and the improved method was compared with the original estimator. A reduction of 11% on the absolute estimation error was obtained for the systole period with the proposed algorithm switching approach.

Antifungal activity of selected indigenous pseudomonas and bacillus from the soybean rhizosphere.

The purpose of this study was to isolate and select indigenous soil Pseudomonas and Bacillus bacteria capable of developing multiple mechanisms of action related to the biocontrol of phytopathogenic fungi affecting soybean crops. The screening procedure consisted of antagonism tests against a panel of phytopathogenic fungi, taxonomic identification, detection by PCR of several genes related to antifungal activity, in vitro detection of the antifungal products, and root colonization assays. Two isolates, identified and designated as Pseudomonas fluorescens BNM296 and Bacillus amyloliquefaciens BNM340, were selected for further studies. These isolates protected plants against the damping-off caused by Pythium ultimum and were able to increase the seedling emergence rate after inoculation of soybean seeds with each bacterium. Also, the shoot nitrogen content was higher in plants when seeds were inoculated with BNM296. The polyphasic approach of this work allowed us to select two indigenous bacterial strains that promoted the early development of soybean plants.

Clustering follow-up time-series recorded by cardiac implantable devices.

Follow-up of patients treated by cardiac resynchronization therapy (CRT) is of great interest to prevent health deterioration in the postoperative period. In this purpose, data recorded in implantable devices (ID) can be informative. They are large, multivariate, evolutive with time, and then difficult to interpret. This study proposes a methodology, based on Multiple Correspondence Analysis (MCA) and fuzzy coding, to i) reduce the dimensionality of these data, ii) characterize the factorial axes by the variables recorded in the ID, iii) identify evolutions of patients in the factorial plane which are related to health deterioration. The results show that the first three axes of the MCA contain more than 90% of the total variance and are linked to the functional state of the patients. A simple clustering of the patients is performed and defines an area of the factorial plane, correlated with a degradation of patients' clinical state.

Thymidine phosphorylase is noncompetitively inhibited by 5'-O-trityl-inosine (KIN59) and related compounds.

We found that 5'-O-trityl-inosine (KIN59) inhibits recombinant bacterial (E. coli) and human thymidine phosphorylase (TPase) with an IC50 of 44 microM and 67 microM, respectively. In contrast to previously described TPase inhibitors, KIN59 does not compete with thymidine (dThd) at the pyrimidine nucleoside-binding site or with inorganic phosphate (Pi) at the phosphate-binding site of the enzyme. These findings are strongly suggestive for the presence of an allosteric binding site at the enzyme. TPase is identical to the angiogenic protein platelet-derived endothelial cell growth factor (PD-ECGF). As such, PD-ECGF stimulates angiogenesis in the chick chorioallantoic membrane (CAM) assay. This angiogenic response was completely inhibited by KIN59. Inosine did not inhibit the enzyme or the angiogenic effect of TPase, confirming that the 5'-O-trityl group in KIN59 is essential for the observed effect. Our observations indicate that allosteric sites in TPase may regulate its biological activity.

Evaluation of real-time QRS detection algorithms in variable contexts.

A method is presented to evaluate the detection performance of real-time QRS detection algorithms to propose a strategy for the adaptive selection of ORS detectors, in variable signal contexts. Signal contexts are defined as different combinations of QRS morphologies and clinical noise. Four QRS detectors are compared in these contexts by means of a multivariate analysis. This evaluation strategy is general and can be easily extended to a larger number of detectors. A set of morphology contexts, corresponding to eight QRS morphologies (normal, PVC, premature atrial beat, paced beat, LBBB, fusion, RBBB, junctional premature beat), was extracted from 17 standard ECG records. For each morphology context, the set of extracted beats, ranging from 30 to 23000, was resampled to generate 50 realisations of 20 concatenated beats. These realisations were then used as input to the QRS detectors, without noise, and with three different types of additive clinical noise (electrode motion artifact, muscle artifact, baseline wander) at three signal-to-noise ratios (5 dB, -5 dB, -15 dB). Performance was assessed by the number of errors, which reflected both false alarms and missed beats. The results show that the evaluated detectors are indeed complementary. For example, the Pan-Tompkins detector is the best in most contexts but the Okada detector generates fewer errors in the presence of electrode motion artifact. These results will be particularly useful to the development of a real-time system that will be able to choose the best ORS detector according to the current context.

A bond graph model of the cardiovascular system.

The study of the autonomic nervous system (ANS) function has shown to provide useful indicators for risk stratification and early detection on a variety of cardiovascular pathologies. However, data gathered during different tests of the ANS are difficult to analyse, mainly due to the complex mechanisms involved in the autonomic regulation of the cardiovascular system (CVS). Although model-based analysis of ANS data has been already proposed as a way to cope with this complexity, only a few models coupling the main elements involved have been presented in the literature. In this paper, a new model of the CVS, representing the ventricles, the circulatory system and the regulation of the CVS activity by the ANS, is presented. The models of the vascular system and the ventricular activity have been developed using the Bond Graph formalism, as it proposes a unified representation for all energetic domains, facilitating the integration of mechanic and hydraulic phenomena. In order to take into account the electro-mechanical behaviour of both ventricles, an electrophysiologic model of the cardiac action potential, represented by a set of ordinary differential equations, has been integrated. The short-term ANS regulation of heart rate, cardiac contractility and peripheral vasoconstriction is represented by means of continuous transfer functions. These models, represented in different continuous formalisms, are coupled by using a multi-formalism simulation library. Results are presented for two different autonomic tests, namely the Tilt Test and the Valsalva Manoeuvre, by comparing real and simulated signals.

Survival and viability of Ascaris suum and Oesophagostomum dentatum in ensiled swine faeces.

The survival and viability of eggs from Ascaris suum and Oesophagostomum dentatum and of infective larvae (L3) from O. dentatum were determined in the ensiled solid fraction of swine faeces after 0, 7, 14, 28 and 56 days of ensiling. The experiment had two treatments, un-ensiled and ensiled manure, in a split-plot design. Each of 50 containers was inoculated with 40,000 eggs of both A. suum and O. dentatum, and another 50 containers were inoculated with 32,747 L3 of O. dentatum each. A. suum eggs were not destroyed by the ensiling process, although their viability was diminished. O. dentatum eggs and larvae were destroyed during the first 7-14 days of the ensiling process.

[Therapeutic efficacy of GM-CSF in pulmonary alveolar proteinosis]. / Eficacia terapéutica del GM-CSF en la proteinosis alveolar pulmonar.

Pulmonary alveolar proteinosis is a rare disease characterized by the deposit of lipid-rich proteinaceous material in alveolar spaces. The only effective treatment known to date has been periodic alveolar lavage, a technique that is laborious and requires that the patient be under general anesthesia, with selective endotracheal-bronchial intubation. Complications are not unknown. Progress in our understandint of the pathogenesis of pulmonary alveolar proteinosis has shown it to be related to changes it to be related to changes in alveolar macrophagocytic capability. We describe a patient in whom 8 weeks of subdermal GM-CSF treatment led to significant clinical, radiologic and lung function improvement.

Increased cAMP immunostaining in cerebral vessels in Alzheimer's disease.

Increasing evidence suggests that up-regulation of the cAMP-second messenger system is implicated in Alzheimer's disease neurodegeneration. Since previous studies reported an increased level of cAMP in microvessels of Alzheimer's patients compared with those from non-demented elderly controls, we have carried out an immunohistochemical study to compare cAMP immunostaining in brain vessels from patients with dementia and neuropathological criteria of Alzheimer's disease (n=5) with those of age-matched patients (n=10). We have also included a control group of adult patients (n=5) to evaluate the role of aging separate from the effects of dementia. Our results demonstrated an increased cAMP immunostaining in cerebral cortical and meningeal vessels from Alzheimer's patients compared to nondemented elderly and adult controls. Vascular cAMP immunostaining was mainly observed in frontal and temporal cortex, the hippocampus being the region that showed the more intense and widespread vascular cAMP immunostaining. We also observed a conspicuous vascular beta-amyloid immunostaining specifically in those vessels that showed the highest cAMP immunostaining. We suggest that increased vascular cAMP immunostaining is mainly localised in the selectively vulnerable targets of neurodegeneration that characterise AD. Moreover, the co-immunolocalisation of cAMP and beta-amyloid protein in cerebral vessels of patients with AD suggests a possible role of cAMP up-regulation in the accumulation of those amyloidogenic peptides.

Real-time ECG transmission via Internet for nonclinical applications.

Telemedicine is producing a great impact in the monitoring of patients located in remote nonclinical environments such as homes, elder communities, gymnasiums, schools, remote military bases, ships, and the like. A number of applications, ranging from data collection, to chronic patient surveillance, and even to the control of therapeutic procedures, are being implemented in many parts of the world. As part of this growing trend, this paper discusses the problems in electrocardiogram (ECG) real-time data acquisition, transmission, and visualization over the Internet. ECG signals are transmitted in real time from a patient in a remote nonclinical environment to the specialist in a hospital or clinic using the current capabilities and availability of the Internet. A prototype system is composed of a portable data acquisition and preprocessing module connected to the computer in the remote site via its RS-232 port, a Java-based client-server platform, and software modules to handle communication protocols between data acquisition module and the patient's personal computer, and to handle client-server communication. The purpose of the system is the provision of extended monitoring for patients under drug therapy after infarction, data collection in some particular cases, remote consultation, and low-cost ECG monitoring for the elderly.

N-Acetylcysteine delays age-associated memory impairment in mice: role in synaptic mitochondria.

Mitochondrial oxidative damage is implicated in brain aging and in age-related neurodegenerative diseases. Since N-acetylcysteine (NAC) has recently been shown to prevent apoptotic death in neuronal cells and protect synaptic mitochondria proteins from oxidative damage in aged mice, we have investigated whether dietary administration of this thiolic antioxidant retards age-related memory loss. At 48 weeks of age, a control female OF-1 mice group was fed standard food pellets and another group received pellets containing 0.3% (w/w) of NAC. After 23 weeks of this diet, the NAC had partially restored the memory deficit associated with aging in mice. Moreover, the lipid peroxide and protein carbonyl contents of the synaptic mitochondria were significantly decreased in the NAC-supplemented animals in comparison with their age-matched controls. The antioxidant properties and probable action on mitochondrial bioenergetic ability in the synaptic terminals may explain, at least partially, the beneficial action of NAC administration.

Overview of CARMEM: a new dynamic quantitative cardiac model for ECG monitoring and its adaptation to observed signals.

Different approaches have been proposed in order to achieve knowledge integration for coronary care monitoring applications, usually in the form of expert systems. The clinical impact of these expert systems, which are based only on "shallow" knowledge, has not been remarkable due to the difficulties associated with the construction and maintenance of a complete knowledge base. Model-based systems represent an alternative to these problems because they allow efficient integration of the "deep" knowledge on the underlying physiological phenomena being monitored. In this work, a brief review of existing model-based systems for cardiac rhythm interpretation is presented, followed by the description of a new system for Cardiac Arrhythmia Recognition by Model-Based ECG Matching (CARMEM). Fundamental characteristics of CARMEM are presented; in particular, its ability to provide online parameter adaptation to simulate complex rhythms and to match observed ECG signals. The proposed model can be useful for the explanation of the origin of cardiac arrhythmias and contribute towards their robust characterization in the context of coronary care units.

Multisensor fusion for atrial and ventricular activity detection in coronary care monitoring.

Information management for critical care monitoring is still a very difficult task. Medical staff is often overwhelmed by the amount of data provided by the increased number of specific monitoring devices and instrumentation, and the lack of an effective automated system. Specifically, a basic task such as arrhythmia detection still produce an important amount of undesirable alarms, due in part to the mechanistic approach of current monitoring systems. In this work, multisensor and multisource data fusion schemes to improve atrial and ventricular activity detection in critical care environments are presented. Applications of these schemes are quantitatively evaluated and compared with current methods, showing the potential advantages of data fusion techniques for event detection in noise corrupted signals.

Hypothesis: can N-acetylcysteine be beneficial in Parkinson's disease?

Based on the finding of decreased mitochondrial complex I activity in the substantia nigra of patients with Parkinson's disease, we propose that the consequent reduction of ATP synthesis and increased generation of reactive oxygen species may be a possible cause of nigrostriatal cell death. Since sulfhydryl groups are essential in oxidative phosphorylation, thiolic antioxidants may contribute to the preservation of these proteins against oxidative damage. In the present paper, we hypothesize that treatment with a sulfur-containing antioxidant such as N-acetylcysteine may provide a new neuroprotective therapeutic strategy for Parkinson's disease.

N-acetylcysteine protects against age-related increase in oxidized proteins in mouse synaptic mitochondria.

Since it has been proposed that oxidized protein accumulation plays a critical role in brain aging, we have investigated the effect of a thiolic antioxidant on protein carbonyl content in synaptic mitochondria from female OF-1 mice. At 48 weeks of age, a control group was fed standard food pellets and another group received pellets containing 0.3% (w/w) of N-acetylcysteine. A 24-week treatment resulted in a significant decrease in protein carbonyl content in synaptic mitochondria of the N-acetylcysteine-treated animals as compared to age-matched controls.

Age-related increase in oxidized proteins in mouse synaptic mitochondria.

Since it has been proposed that oxidized protein accumulation plays a critical role in brain aging, we have investigated their contents in synaptic mitochondria from five age groups of mice. Protein carbonyl content in synaptic mitochondria showed a significant positive correlation with age (r = 0.95, P = 0.01). A linear inverse relationship was observed between protein carbonyl content and complex IV/complex I ratio (which was used as an index of imbalance between mitochondrial respiratory complexes) in synaptic mitochondria in the five age groups (r = -0.99, P < 0.001). We suggest that age-related accumulation of oxidized proteins in synaptic mitochondria may be the result of an age-dependent increase in reactive oxygen species generation because of a disarrangement of mitochondrial oxidative phosphorylation.