Exercise training in childhood-onset systemic lupus erythematosus: a controlled randomized trial

Introduction

Exercise training has emerged as a promising therapeutic strategy to counteract physical dysfunction in adult systemic lupus erythematosus. However, no longitudinal studies have evaluated the effects of an exercise training program in childhood-onset systemic lupus erythematosus (C-SLE) patients. The objective was to evaluate the safety and the efficacy of a supervised aerobic training program in improving the cardiorespiratory capacity in C-SLE patients.

Methods

Nineteen physically inactive C-SLE patients were randomly assigned into two groups: trained (TR, n = 10, supervised moderate-intensity aerobic exercise program) and non-trained (NT, n = 9). Gender-, body mass index (BMI)- and age-matched healthy children were recruited as controls (C, n = 10) for baseline (PRE) measurements only. C-SLE patients were assessed at PRE and after 12 weeks of training (POST). Main measurements included exercise tolerance and cardiorespiratory measurements in response to a maximal exercise (that is, peak VO₂, chronotropic reserve (CR), and the heart rate recovery (ΔHRR) (that is, the difference between HR at peak exercise and at both the first (ΔHRR1) and second (ΔHRR2) minutes of recovery after exercise).

Results

The C-SLE NT patients did not present changes in any of the cardiorespiratory parameters at POST (P > 0.05). In contrast, the exercise training program was effective in promoting significant increases in time-to-exhaustion (P = 0.01; ES = 1.07), peak speed (P = 0.01; ES = 1.08), peak VO₂ (P = 0.04; ES = 0.86), CR (P = 0.06; ES = 0.83), and in ΔHRR1 and ΔHRR2 (P = 0.003; ES = 1.29 and P = 0.0008; ES = 1.36, respectively) in the C-SLE TR when compared with the NT group. Moreover, cardiorespiratory parameters were comparable between C-SLE TR patients and C subjects after the exercise training intervention, as evidenced by the ANOVA analysis (P > 0.05, TR vs. C). SLEDAI-2K scores remained stable throughout the study.

Conclusion

A 3-month aerobic exercise training was safe and capable of ameliorating the cardiorespiratory capacity and the autonomic function in C-SLE patients.

Trial registration

NCT01515163.     

Cardiorespiratory Information Dynamics during Mental Arithmetic and Sustained Attention

An analysis of cardiorespiratory dynamics during mental arithmetic, which induces stress, and sustained attention was conducted using information theory. The information storage and internal information of heart rate variability (HRV) were determined respectively as the self-entropy of the tachogram, and the self-entropy of the tachogram conditioned to the knowledge of respiration. The information transfer and cross information from respiration to HRV were assessed as the transfer and cross-entropy, both measures of cardiorespiratory coupling. These information-theoretic measures identified significant nonlinearities in the cardiorespiratory time series. Additionally, it was shown that, although mental stress is related to a reduction in vagal activity, no difference in cardiorespiratory coupling was found when several mental states (rest, mental stress, sustained attention) are compared. However, the self-entropy of HRV conditioned to respiration was very informative to study the predictability of RR interval series during mental tasks, and showed higher predictability during mental arithmetic compared to sustained attention or rest.     

Mixed predictability and cross-validation to assess non-linear Granger causality in short cardiovascular variability series.

A method to evaluate the direction and strength of causal interactions in bivariate cardiovascular and cardiorespiratory series is presented. The method is based on quantifying self and mixed predictability of the two series using nearest-neighbour local linear approximation. It returns two causal coupling indexes measuring the relative improvement in predictability along direct and reverse directions, and a directionality index indicating the preferential direction of interaction. The method was implemented through a cross-validation approach that allowed quantification of directionality without constraining the embedding of the series, and fully exploited the available data to maximise the prediction accuracy. Validation on short simulated bivariate time series demonstrated the ability of the method to capture different degrees of unidirectional and bidirectional interaction. Moreover, application to representative examples of heart rate, systolic arterial pressure and respiration series allowed the inference of causal relationships related to known physiological mechanisms and experimental conditions.     

Spatiotemporal Evolution of Ebola Virus Disease at Sub-National Level during the 2014 West Africa Epidemic: Model Scrutiny and Data Meagreness

Background

The Ebola outbreak in West Africa has infected at least 27,443 individuals and killed 11,207, based on data until 24 June, 2015, released by the World Health Organization (WHO). This outbreak has been characterised by extensive geographic spread across the affected countries Guinea, Liberia and Sierra Leone, and by localized hotspots within these countries. The rapid recognition and quantitative assessment of localised areas of higher transmission can inform the optimal deployment of public health resources.

Methods

A variety of mathematical models have been used to estimate the evolution of this epidemic, and some have pointed out the importance of the spatial heterogeneity apparent from incidence maps. However, little is known about the district-level transmission. Given that many response decisions are taken at sub-national level, the current study aimed to investigate the spatial heterogeneity by using a different modelling framework, built on publicly available data at district level. Furthermore, we assessed whether this model could quantify the effect of intervention measures and provide predictions at a local level to guide public health action. We used a two-stage modelling approach: a) a flexible spatiotemporal growth model across all affected districts and b) a deterministic SEIR compartmental model per district whenever deemed appropriate.

Findings

Our estimates show substantial differences in the evolution of the outbreak in the various regions of Guinea, Liberia and Sierra Leone, illustrating the importance of monitoring the outbreak at district level. We also provide an estimate of the time-dependent district-specific effective reproduction number, as a quantitative measure to compare transmission between different districts and give input for informed decisions on control measures and resource allocation. Prediction and assessing the impact of control measures proved to be difficult without more accurate data. In conclusion, this study provides us a useful tool at district level for public health, and illustrates the importance of collecting and sharing data.     

Automated Entire Thrombus Density Measurements for Robust and Comprehensive Thrombus Characterization in Patients with Acute Ischemic Stroke

Background and Purpose

In acute ischemic stroke (AIS) management, CT-based thrombus density has been associated with treatment success. However, currently used thrombus measurements are prone to inter-observer variability and oversimplify the heterogeneous thrombus composition. Our aim was first to introduce an automated method to assess the entire thrombus density and then to compare the measured entire thrombus density with respect to current standard manual measurements.

Materials and Method

In 135 AIS patients, the density distribution of the entire thrombus was determined. Density distributions were described using medians, interquartile ranges (IQR), kurtosis, and skewedness. Differences between the median of entire thrombus measurements and commonly applied manual measurements using 3 regions of interest were determined using linear regression.

Results

Density distributions varied considerably with medians ranging from 20.0 to 62.8 HU and IQRs ranging from 9.3 to 55.8 HU. The average median of the thrombus density distributions (43.5 ± 10.2 HU) was lower than the manual assessment (49.6 ± 8.0 HU) (p<0.05). The difference between manual measurements and median density of entire thrombus decreased with increasing density (r = 0.64; p<0.05), revealing relatively higher manual measurements for low density thrombi such that manual density measurement tend overestimates the real thrombus density.

Conclusions

Automatic measurements of the full thrombus expose a wide variety of thrombi density distribution, which is not grasped with currently used manual measurement. Furthermore, discrimination of low and high density thrombi is improved with the automated method.     

A grapevine (<Emphasis Type="Italic">Vitis vinifera</Emphasis> L.) genetic map integrating the position of 139 expressed genes

Grapevine molecular maps based on microsatellites, AFLP and RAPD markers are now available. SSRs are essential to allow cross-talks between maps, thus upgrading any growing grapevine maps. In this work, single nucleotide polymorphisms (SNPs) were developed from coding sequences and from unique BAC-end sequences, and nested in a SSR framework map of grapevine. Genes participating to flavonoids metabolism and defence, and signal transduction pathways related genes were also considered. Primer pairs for 351 loci were developed from ESTs present on public databases and screened for polymorphism in the “Merzling” (a complex genotype Freiburg 993–60 derived from multiple crosses also involving wild Vitis species) × Vitis vinifera (cv. Teroldego) cross population. In total 138 SNPs, 108 SSR markers and a phenotypic trait (berry colour) were mapped in 19 major linkage groups of the consensus map. In specific cases, ESTs with putatively related functions mapped near QTLs previously identified for resistance and berry ripening. Genes related to anthocyanin metabolism mapped in different linkage groups. A myb gene, which has been correlated with anthocyanin biosynthesis, cosegregated with berry colour on linkage group 2. The possibility of associating candidate genes to known position of QTL is discussed for this plant. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. Marzia Salmaso and Giulia Malacarne contributed equally to the present work.     

Multivariate EEG spectral analysis evidences the functional link between motor and visual cortex during integrative sensorimotor tasks

The identification of the networks connecting brain areas and the understanding of their role in executing complex tasks is a crucial issue in cognitive neuroscience. In this study, specific visuomotor tasks were devised to reveal the functional network underlying the cooperation process between visual and motor regions. Electroencephalography (EEG) data were recorded from twelve healthy subjects during a combined visuomotor task, which integrated precise grip motor commands with sensory visual feedback (VM). This condition was compared with control tasks involving pure motor action (M), pure visual perception (V) and visuomotor performance without feedback (V + M). Multivariate parametric cross-spectral analysis was applied to ten EEG derivations in each subject to assess changes in the oscillatory activity of the involved cortical regions and quantify their coupling. Spectral decomposition was applied to precisely and objectively determine the power associated with each oscillatory component of the spectrum, while surrogate data analysis was performed to assess the statistical significance of estimated coherence values. A significant decrease of the alpha and/or beta power in EEG spectra with respect to rest values was assumed as indicative of specific cortical area activation during task execution. Indeed alpha band coherence increased in proximity of task-involved areas, while it was suppressed or remained unchanged in other regions, suggesting the activation of a specific network for each task. According to our coherence analysis, a direct link between visual and motor areas was activated during V + M and VM tasks. The effect of visual feedback was evident in the beta band, where the increase of coherence was observed only during the VM task. Multivariate analysis suggested the presence of a functional link between motor and visual cortex subserving sensorimotor integration. Furthermore, network activation was related to the sum of single task (M and V) local effects in the alpha band, and to the presence of visual feedback in the beta band.     

Towards a framework for the evolutionary genomics of Kinetoplastids: what kind of data and how much?

The current status of kinetoplastids phylogeny and evolution is discussed in view of the recent progresses on genomics. Some ideas on a potential framework for the evolutionary genomics of kinetoplastids are presented.