Quantification of Linear and Nonlinear Cardiorespiratory Interactions under Autonomic Nervous System Blockade

This paper proposes a methodology to extract both linear and nonlinear respiratory influences from the heart rate variability (HRV), by decomposing the HRV into a respiratory and a residual component. This methodology is based on least-squares support vector machines (LS-SVM) formulated for nonlinear function estimation. From this decomposition, a better estimation of the respiratory sinus arrhythmia (RSA) and the sympathovagal balance (SB) can be achieved. These estimates are first analyzed during autonomic blockade and an orthostatic maneuver, and then compared against the classical HRV and a model that considers only linear interactions. Results are evaluated using surrogate data analysis and they indicate that the classical HRV and the linear model underestimate the cardiorespiratory interactions. Moreover, the linear and nonlinear interactions appear to be mediated by different control mechanisms. These findings will allow to better assess the ANS and to improve the understanding of the interactions within the cardiorespiratory system

Effect of the Heart Rate Variability Representations on the Quantification of the Cardiorespiratory Interactions during Autonomic Nervous System Blockade

The Heart Rate Variability (HRV) is a noninvasive tool to evaluate the activity of the autonomic nervous system. To study the HRV, different mathematical representations can be used. The selection of a representation might have an effect on the evaluation of the mechanisms that modulate the Heart Rate (HR). One of these mechanisms is the Respiratory Sinus Arrhythmia (RSA), i.e. an increased HR during inhalation and a decreased HR during exhalation. Different methods exist to quantify the RSA. A common approach is to calculate the power in the High Frequency (HF, 0.15 - 0.4 Hz) band of the spectrum of the HRV representation. More recently proposed methods use the respiratory signals to estimate the strength of the RSA.This paper studies the effect of the HRV representations on the quantification of the RSA. To this end, an experiment is used in which the sympathetic and parasympathetic branches of the autonomic nervous system are selectively blocked. Three different HRV representations are considered. Afterwards, the strength of the RSA is estimated using three approaches, namely the spectral content in the HF band of the HRV representations, orthogonal subspace projections and a time-frequency representation.The results suggest that the selection of an HRV representation does not have a significant impact on the RSA estimates in a healthy population

Treatment of von Willebrand disease

Summary. von Willebrand disease is the most frequent of inherited bleeding disorders (1:100 affected individuals in the general population). The aim of treatment is to correct the dual defects of haemostasis, i.e., abnormal coagulation expressed by low levels of factor VIII and abnormal platelet adhesion expressed by a prolonged bleeding time. There are two main options available for the management of von Willebrand disease: desmopressin and transfusion therapy with blood products. Desmopressin is the treatment of choice in patients with type 1 von Willebrand disease, who account for approximately 80% of cases. This pharmacological compound raises endogenous factor VIII and von Willebrand factors and thereby corrects the intrinsic coagulation defect and the prolonged bleeding time in most type 1 patients. In type 3 and in the majority of type 2 patients desmopressin is not effective, and it is necessary to resort to plasma concentrates containing factor VIII and von Willebrand factor. Treated with virucidal methods, these concentrates are effective and currently safe, but the bleeding time defect is not always corrected by them. Platelet concentrates or desmopressin can be used as adjunctive treatments when poor correction of the bleeding time after concentrates is associated with continued bleeding

FGF4 retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs.

Chondrodystrophy in dogs is defined by dysplastic, shortened long bones and premature degeneration and calcification of intervertebral discs. Independent genome-wide association analyses for skeletal dysplasia (short limbs) within a single breed (PBonferroni = 0.01) and intervertebral disc disease (IVDD) across breeds (PBonferroni = 4.0 × 10-10) both identified a significant association to the same region on CFA12. Whole genome sequencing identified a highly expressed FGF4 retrogene within this shared region. The FGF4 retrogene segregated with limb length and had an odds ratio of 51.23 (95% CI = 46.69, 56.20) for IVDD. Long bone length in dogs is a unique example of multiple disease-causing retrocopies of the same parental gene in a mammalian species. FGF signaling abnormalities have been associated with skeletal dysplasia in humans, and our findings present opportunities for both selective elimination of a medically and financially devastating disease in dogs and further understanding of the ever-growing complexity of retrogene biology

Heart Rate Variability Analysis Assessment for Asthma Control Stratification

Autonomic nervous system (ANS) has been suggested to play a major role in the pathogenesis of asthma. This hypothesis has motivated large research, revealing a reduced modulation of the heart rate in subjects with uncontrolled asthma, when compared to asthmatics with controlled symptomatology. In this work, we assessed ANS activity through heart rate variability analysis in a group of asthmatics classified attending to the control of their symptoms. This information was later used for training a logistic regression classifier aiming at differentiating between the levels of control in asthmatic patients. The accuracy of the classifier improved when including ANS information (71.77%, versus 64.73% when only clinical parameters were considered), suggesting that ANS assessment could contribute to better non-invasive asthma monitoring

Helicobacter pullorum cytolethal distending toxin targets vinculin and cortactin and triggers formation of lamellipodia in intestinal epithelial cells

Helicobacter pullorum, a bacterium initially isolated from poultry, has been associated with human digestive disorders. However, the factor responsible for its cytopathogenic effects on epithelial cells has not been formally identified. The cytopathogenic alterations induced by several human and avian H. pullorum strains were investigated on human intestinal epithelial cell lines. Moreover, the effects of the cytolethal distending toxin (CDT) were evaluated first by using a wild-type strain and its corresponding cdtB isogenic mutant and second by delivering the active CdtB subunit of the CDT directly into the cells. All of the H. pullorum strains induced cellular distending phenotype, actin cytoskeleton remodeling, and G2/M cell cycle arrest. These effects were dependent on the CDT, as they were (1) not observed in response to a cdtB isogenic mutant strain and (2) present in cells expressing CdtB. CdtB also induced an atypical delocalization of vinculin from focal adhesions to the perinuclear region, formation of cortical actin-rich large lamellipodia with an upregulation of cortactin, and decreased cellular adherence. In conclusion, the CDT of H. pullorum is responsible for major cytopathogenic effects in vitro, confirming its role as a main virulence factor of this emerging human pathogen.This work was supported by the Institut national de la santé et de la recherche médicale, the University Bordeaux Segalen, the Conseil Régional d’Aquitaine (grants 20030304002FA and 20040305003 FA), the Société Nationale Française de Gastroentérologie, the European Union (FEDER no. 2003227

On the 'centre of gravity' method for measuring the composition of magnetite/maghemite mixtures, or the stoichiometry of magnetite-maghemite solid solutions, via Fe-57 Mossbauer spectroscopy

We evaluate the application of 57Fe Mössbauer spectroscopy to the determination of the composition of magnetite (Fe3O4)/maghemite (γ-Fe2O3) mixtures and the stoichiometry of magnetite-maghemite solid solutions. In particular, we consider a recently proposed model-independent method which does not rely on a priori assumptions regarding the nature of the sample, other than that it is free of other Fe-containing phases. In it a single parameter, δRT—the ‘centre of gravity’, or area weighted mean isomer shift at room temperature, T = 295 ± 5 K—is extracted by curve-fitting a sample’s Mössbauer spectrum, and is correlated to the sample’s composition or stoichiometry. We present data on highpurity magnetite and maghemite powders, and mixtures thereof, as well as comparison literature data from nanoparticulate mixtures and solid solutions, to show that a linear correlation exists between δRT and the numerical proportion of Fe atoms in the magnetite environment: α = Femagnetite/Fetotal = − ( ) δ δ RT o /m, where δo = 0.3206 ± 0.0022mm s−1 and m = 0.2135 ± 0.0076mm s−1 . We also present equations to relate α to the weight percentage w of magnetite in mixed phases, and the magnetite stoichiometry x = Fe2+/Fe3+ in solid solutions. The analytical method is generally applicable, but is most accurate when the absorption profiles are sharp; in some samples this may require spectra to be recorded at reduced temperatures. We consider such cases and provide equations to relate δ ( ) T to the corresponding α value

Evaluation of Methods to Characterize the Change of the Respiratory Sinus Arrhythmia with Age in Sleep Apnea Patients

The High Frequency (HF) band of the power spectrum of the Heart Rate Variability (HRV) is widely accepted to contain information related to the respiration. However, it is known that this often results in misleading estimations of the strength of the Respiratory Sinus Arrhythmia (RSA). In this paper, different approaches to characterize the change of the RSA with age, combining HRV and respiratory signals, are studied. These approaches are the bandwidths in the power spectral density estimations, bivariate phase rectified signal averaging, information dynamics, a time-frequency representation, and a heart rate decomposition based on subspace projections. They were applied to a dataset of sleep apnea patients, specifically to periods without apneas and during NREM sleep. Each estimate reflected a different relationship between RSA and age, suggesting that they all capture the cardiorespiratory information in a different way. The comparison of the estimates indicates that the approaches based on the extraction of respiratory information from HRV provide a better characterization of the age-dependent degradation of the RSA