Analysis of metabolomic data: tools, current strategies and future challenges for omics data integration

Metabolomics is a rapidly growing field consisting of the analysis of a large number of metabolites at a system scale. The two major goals of metabolomics are the identification of the metabolites characterizing each organism state and the measurement of their dynamics under different situations (e.g. pathological conditions, environmental factors). Knowledge about metabolites is crucial for the understanding of most cellular phenomena, but this information alone is not sufficient to gain a comprehensive view of all the biological processes involved. Integrated approaches combining metabolomics with transcriptomics and proteomics are thus required to obtain much deeper insights than any of these techniques alone. Although this information is available, multilevel integration of different 'omics' data is still a challenge. The handling, processing, analysis and integration of these data require specialized mathematical, statistical and bioinformatics tools, and several technical problems hampering a rapid progress in the field exist. Here, we review four main tools for number of users or provided features (MetaCore(TM), MetaboAnalyst, InCroMAP and 3Omics) out of the several available for metabolomic data analysis and integration with other 'omics' data, highlighting their strong and weak aspects; a number of related issues affecting data analysis and integration are also identified and discussed. Overall, we provide an objective description of how some of the main currently available software packages work, which may help the experimental practitioner in the choice of a robust pipeline for metabolomic data analysis and integration

FATIGUE ALTERS THE BIOMECHANICS OF TURNS WHILE RUNNING

This study identified the effects of fatigue on lower limb kinematics while running with repeated 180°-turns. An increased stiffness of the pivoting limb was observed in terms of a reduction of hip and knee flexion angles, and an increase of hip abduction and internal rotation. We concluded that muscle fatigue can trigger a sequence of adaptations that were previously found to expose the athlete to an increasing risk of ligament injury. These results expand the base of evidence for the development of field-based prevention programs

Autonomic and circulatory alterations persist despite adequate resuscitation in a 5-day sepsis swine experiment.

Autonomic and vascular failures are common phenotypes of sepsis, typically characterized by tachycardia despite corrected hypotension/hypovolemia, vasopressor resistance, increased arterial stiffness and decreased peripheral vascular resistance. In a 5-day swine experiment of polymicrobial sepsis we aimed at characterizing arterial properties and autonomic mechanisms responsible for cardiovascular homeostasis regulation, with the final goal to verify whether the resuscitation therapy in agreement with standard guidelines was successful in restoring a physiological condition of hemodynamic profile, cardiovascular interactions and autonomic control. Twenty pigs were randomized to polymicrobial sepsis and protocol-based resuscitation or to prolonged mechanical ventilation and sedation without sepsis. The animals were studied at baseline, after sepsis development, and every 24 h during the 3-days resuscitation period. Beat-to-beat carotid blood pressure (BP), carotid blood flow, and central venous pressure were continuously recorded. The two-element Windkessel model was adopted to study carotid arterial compliance, systemic vascular resistance and characteristic time constant τ. Effective arterial elastance was calculated as a simple estimate of total arterial load. Cardiac baroreflex sensitivity (BRS) and low frequency (LF) spectral power of diastolic BP were computed to assess autonomic activity. Sepsis induced significant vascular and autonomic alterations, manifested as increased arterial stiffness, decreased vascular resistance and τ constant, reduced BRS and LF power, higher arterial afterload and elevated heart rate in septic pigs compared to sham animals. This compromised condition was persistent until the end of the experiment, despite achievement of recommended resuscitation goals by administered vasopressors and fluids. Vascular and autonomic alterations persist 3 days after goal-directed resuscitation in a clinically relevant sepsis model. We hypothesize that the addition of these variables to standard clinical markers may better profile patients' response to treatment and this could drive a more tailored therapy which could have a potential impact on long-term outcomes

Low-Intensity Whole-Body Vibration: A Useful Adjuvant in Managing Obesity? A Pilot Study

The use of whole-body vibration (WBV) for therapeutic purposes is far from being stan- dardized and an empirical foundation for reporting guidelines for human WBV studies has only very recently been published. Controversies about safety and therapeutic dosage still exist. The present study aimed to investigate the metabolic and mechanical effects of low-intensity WBV according to the ISO 2631 norm on subjects with obesity. Forty-one obese subjects (BMI ≥35 kg/m2) were recruited to participate in a 3-week multidisciplinary inpatient rehabilitation program including fitness training and WBV training. During WBV the posture was monitored with an optoelectronic system with six infrared cameras (Vicon, Vicon Motion System, Oxford, UK). The primary endpoints were: variation in body composition, factors of metabolic syndrome, functional activity (sit-to-stand and 6-min walking test), muscle strength, and quality of life. The secondary endpoints were: mod- ification of irisin, testosterone, growth hormone, IGF1 levels. We observed significant changes in salivary irisin levels, Group 2 (p < 0.01) as compared to the control group, while muscle strength, function, and other metabolic and hormonal factors did not change after a 3-week low-intensity WBV training with respect to the control group. Future studies are needed to further investigate the potential metabolic effect of low-intensity WBV in managing weight

The Forgotten Role of Central Volume in Low Frequency Oscillations of Heart Rate Variability

The hypothesis that central volume plays a key role in the source of low frequency (LF) oscillations of heart rate variability (HRV) was tested in a population of end stage renal disease patients undergoing conventional hemodialysis (HD) treatment, and thus subject to large fluid shifts and sympathetic activation. Fluid overload (FO) in 58 chronic HD patients was assessed by whole body bioimpedance measurements before the midweek HD session. Heart Rate Variability (HRV) was measured using 24-hour Holter electrocardiogram recordings starting before the same HD treatment. Time domain and frequency domain analyses were performed on HRV signals. Patients were retrospectively classified in three groups according to tertiles of FO normalized to the extracellular water (FO/ECW%). These groups were also compared after stratification by diabetes mellitus. Patients with the low to medium hydration status before the treatment (i.e. 1st and 2nd FO/ECW% tertiles) showed a significant increase in LF power during last 30 min of HD compared to dialysis begin, while no significant change in LF power was seen in the third group (i.e. those with high pre-treatment hydration values). In conclusion, several mechanisms can generate LF oscillations in the cardiovascular system, including baroreflex feedback loops and central oscillators. However, the current results emphasize the role played by the central volume in determining the power of LF oscillations

Blood pressure variability, heart functionality, and left ventricular tissue alterations in a protocol of severe hemorrhagic shock and resuscitation

Autonomic control of blood pressure (BP) and heart rate (HR) is crucial during bleeding and hemorrhagic shock (HS) to compensate for hypotension and hypoxia. Previous works have observed that at the point of hemodynamic decompensation a marked suppression of BP and HR variability occurs, leading to irreversible shock. We hypothesized that recovery of the autonomic control may be decisive for effective resuscitation, along with restoration of mean BP. We computed cardiovascular indexes of baroreflex sensitivity and BP and HR variability by analyzing hemodynamic recordings collected from five pigs during a protocol of severe hemorrhage and resuscitation; three pigs were sham-treated controls. Moreover, we assessed the effects of severe hemorrhage on heart functionality by integrating the hemodynamic findings with measures of plasma high-sensitivity cardiac troponin T and metabolite concentrations in left ventricular (LV) tissue. Resuscitation was performed with fluids and norepinephrine and then by reinfusion of shed blood. After first resuscitation, mean BP reached the target value, but cardiovascular indexes were not fully restored, hinting at a partial recovery of the autonomic mechanisms. Moreover, cardiac troponins were still elevated, suggesting a persistent myocardial sufferance. After blood reinfusion all the indexes returned to baseline. In the harvested heart, LV metabolic profile confirmed the acute stress condition sensed by the cardiomyocytes. Variability indexes and baroreflex trends can be valuable tools to evaluate the severity of HS, and they may represent a more useful end point for resuscitation in combination with standard measures such as mean values and biological measures. NEW & NOTEWORTHY Autonomic control of blood pressure was highly impaired during hemorrhagic shock, and it was not completely recovered after resuscitation despite global restoration of mean pressures. Moreover, a persistent myocardial sufferance emerged from measured cardiac troponin T and metabolite concentrations of left ventricular tissue. We highlight the importance of combining global mean values and biological markers with measures of variability and autonomic control for a better characterization of the effectiveness of the resuscitation strategy

Recent Advances and Novel Ideas for High Brightness Electron Beam Production Based on Photo-Injectors

Photo-injectors beam physics remains a fruitful and exciting field of research. New ideas have been recently proposed to achieve ultra-high brightness beams, as particularly needed in SASE-FEL experiments, and to produce flat beams as required in linear colliders. An overview of recent advancements in photo-injector beam physics is reported in this paper

An Innovative Approach for the Integration of Proteomics and Metabolomics Data in Severe Septic Shock Patients Stratified for Mortality

Abstract In this work, we examined plasma metabolome, proteome and clinical features in patients with severe septic shock enrolled in the multicenter ALBIOS study. The objective was to identify changes in the levels of metabolites involved in septic shock progression and to integrate this information with the variation occurring in proteins and clinical data. Mass spectrometry-based targeted metabolomics and untargeted proteomics allowed us to quantify absolute metabolites concentration and relative proteins abundance. We computed the ratio D7/D1 to take into account their variation from day 1 (D1) to day 7 (D7) after shock diagnosis. Patients were divided into two groups according to 28-day mortality. Three different elastic net logistic regression models were built: one on metabolites only, one on metabolites and proteins and one to integrate metabolomics and proteomics data with clinical parameters. Linear discriminant analysis and Partial least squares Discriminant Analysis were also implemented. All the obtained models correctly classified the observations in the testing set. By looking at the variable importance (VIP) and the selected features, the integration of metabolomics with proteomics data showed the importance of circulating lipids and coagulation cascade in septic shock progression, thus capturing a further layer of biological information complementary to metabolomics information

Complexity analysis of the fetal heart rate variability: early identification of severe intrauterine growth-restricted fetuses

The main goal of this work is to suggest new indices for a correct identification of the intrauterine growth-restricted (IUGR) fetuses on the basis of fetal heart rate (FHR) variability analysis performed in the antepartum period. To this purpose, we analyzed 59 FHR time series recorded in early periods of gestation through a Hewlett Packard 1351A cardiotocograph. Advanced analysis techniques were adopted including the computation of the Lempel Ziv complexity (LZC) index and the multiscale entropy (MSE), that is, the entropy estimation with a multiscale approach. A multiparametric classifier based on k-mean cluster analysis was also performed to separate pathological and normal fetuses. The results show that the proposed LZC and the MSE could be useful to identify the actual IUGRs and to separate them from the physiological fetuses, providing good values of sensitivity and accuracy (Se = 77.8%, Ac = 82.4%)