Evaluation of physiologic complexity in time series using generalized sample entropy and surrogate data analysis

Complexity in time series is an intriguing feature of living dynamical systems, with potential use for identification of system state. Although various methods have been proposed for measuring physiologic complexity, uncorrelated time series are often assigned high values of complexity, errouneously classifying them as a complex physiological signals. Here, we propose and discuss a method for complex system analysis based on generalized statistical formalism and surrogate time series. Sample entropy (SampEn) was rewritten inspired in Tsallis generalized entropy, as function of q parameter (qSampEn). qSDiff curves were calculated, which consist of differences between original and surrogate series qSampEn. We evaluated qSDiff for 125 real heart rate variability (HRV) dynamics, divided into groups of 70 healthy, 44 congestive heart failure (CHF), and 11 atrial fibrillation (AF) subjects, and for simulated series of stochastic and chaotic process. The evaluations showed that, for nonperiodic signals, qSDiff curves have a maximum point (qSDiff(max)) for q not equal 1. Values of q where the maximum point occurs and where qSDiff is zero were also evaluated. Only qSDiff(max) values were capable of distinguish HRV groups (p-values 5.10 x 10(-3); 1.11 x 10(-7), and 5.50 x 10(-7) for healthy vs. CHF, healthy vs. AF, and CHF vs. AF, respectively), consistently with the concept of physiologic complexity, and suggests a potential use for chaotic system analysis. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4758815]

Posttreatment and physiologic occlusal changes comparison

Objective: To compare posttreatment and postretention occlusal changes with the physiologic occlusal changes caused by natural development of untreated subjects. Materials and Methods: The sample was divided into three groups. Group 1 comprised 97 subjects treated with four premolar extractions at a mean pretreatment (T0) age of 13.03 years, a mean posttreatment (T1, first observation) age of 15.12 years, and a mean postretention (T2, second observation) age of 20.52 years. The mean observation period (T2-T1) was 5.39 years. Group 2 comprised 58 subjects treated nonextraction at a mean pretreatment age of 12.83 years, a mean posttreatment age of 14.99 years, a mean postretention age of 20.22 years, and a mean observation period of 5.22 years. Group 3 comprised 114 untreated subjects at a mean age at T1 of 14.91 years and at T2 of 20.48 years. The mean observation period was 5.56 years. Dental casts were evaluated using the Peer Assessment Rating (PAR) index and the Little irregularity index in maxillary and mandibular arches. Changes in PAR and Little indexes were compared among the three groups by analysis of variance and Tukey tests. Results: Intergroup comparison showed that at T1 and T2 the treated groups presented smaller PAR and Little indexes than the untreated group. In the observation period, the treated groups showed greater increase in PAR and Little maxillary indexes than the untreated group. The extraction group showed a greater increase of the Little mandibular index than the untreated group. Conclusions: The treated groups showed more changes according to PAR and Little maxillary indexes than the untreated group. The posttreatment change of the mandibular anterior crowding of the treated extraction group was greater than the mandibular crowding caused by physiologic changes in the untreated group

Toward optimal display of physiologic status in critical care: I. Recreating bedside displays from archived physiologic data

BACKGROUND: Physiologic data display is essential to decision making in critical care. Current displays echo first-generation hemodynamic monitors dating to the 1970s and have not kept pace with new insights into physiology or the needs of clinicians who must make progressively more complex decisions about their patients. The effectiveness of any redesign must be tested before deployment. Tools that compare current displays with novel presentations of processed physiologic data are required. Regenerating conventional physiologic displays from archived physiologic data is an essential first step. OBJECTIVES: The purposes of the study were to (1) describe the SSSI (single sensor single indicator) paradigm that is currently used for physiologic signal displays, (2) identify and discuss possible extensions and enhancements of the SSSI paradigm, and (3) develop a general approach and a software prototype to construct such "extended SSSI displays" from raw data. RESULTS: We present Multi Wave Animator (MWA) framework-a set of open source MATLAB (MathWorks, Inc., Natick, MA, USA) scripts aimed to create dynamic visualizations (eg, video files in AVI format) of patient vital signs recorded from bedside (intensive care unit or operating room) monitors. Multi Wave Animator creates animations in which vital signs are displayed to mimic their appearance on current bedside monitors. The source code of MWA is freely available online together with a detailed tutorial and sample data sets.

Physiologic response to changing positive end-expiratory pressure during neurally adjusted ventilatory assist in sedated, critically ill adults

Neurally adjusted ventilatory assist (NAVA) delivers airway pressure (Paw) in proportion to neural inspiratory drive as reflected by electrical activity of the diaphragm (EAdi). Changing positive end-expiratory pressure (PEEP) impacts respiratory muscle load and function and, hence, EAdi. We aimed to evaluate how PEEP affects the breathing pattern and neuroventilatory efficiency during NAVA.

Estimation of physiologic ability and surgical stress score does not predict immediate outcome after pancreatic surgery

The Estimation of Physiologic Ability and Surgical Stress score was designed to predict postoperative morbidity and mortality in general surgery. Our study aims to evaluate its use and accuracy in estimating postoperative outcome after elective pancreatic surgery.

Physiologic cold shock of Moraxella catarrhalis affects the expression of genes involved in the iron acquisition, serum resistance and immune evasion

Background Moraxella catarrhalis, a major nasopharyngeal pathogen of the human respiratory tract, is exposed to rapid downshifts of environmental temperature when humans breathe cold air. It was previously shown that the prevalence of pharyngeal colonization and respiratory tract infections caused by M. catarrhalis are greatest in winter. The aim of this study was to investigate how M. catarrhalis uses the physiologic exposure to cold air to upregulate pivotal survival systems in the pharynx that may contribute to M. catarrhalis virulence. Results A 26°C cold shock induces the expression of genes involved in transferrin and lactoferrin acquisition, and enhances binding of these proteins on the surface of M. catarrhalis. Exposure of M. catarrhalis to 26°C upregulates the expression of UspA2, a major outer membrane protein involved in serum resistance, leading to improved binding of vitronectin which neutralizes the lethal effect of human complement. In contrast, cold shock decreases the expression of Hemagglutinin, a major adhesin, which mediates B cell response, and reduces immunoglobulin D-binding on the surface of M. catarrhalis. Conclusion Cold shock of M. catarrhalis induces the expression of genes involved in iron acquisition, serum resistance and immune evasion. Thus, cold shock at a physiologically relevant temperature of 26°C induces in M. catarrhalis a complex of adaptive mechanisms that enables the bacterium to target their host cellular receptors or soluble effectors and may contribute to enhanced growth, colonization and virulence.

Postreperfusion cardiac arrest and resuscitation during orthotopic liver transplantation: dynamic visualization and analysis of physiologic recordings

We recently reported on the Multi Wave Animator (MWA), a novel open-source tool with capability of recreating continuous physiologic signals from archived numerical data and presenting them as they appeared on the patient monitor. In this report, we demonstrate for the first time the power of this technology in a real clinical case, an intraoperative cardiopulmonary arrest following reperfusion of a liver transplant graft. Using the MWA, we animated hemodynamic and ventilator data acquired before, during, and after cardiac arrest and resuscitation. This report is accompanied by an online video that shows the most critical phases of the cardiac arrest and resuscitation and provides a basis for analysis and discussion. This video is extracted from a 33-min, uninterrupted video of cardiac arrest and resuscitation, which is available online. The unique strength of MWA, its capability to accurately present discrete and continuous data in a format familiar to clinicians, allowed us this rare glimpse into events leading to an intraoperative cardiac arrest. Because of the ability to recreate and replay clinical events, this tool should be of great interest to medical educators, researchers, and clinicians involved in quality assurance and patient safety.

The physiologic increase in expression of some type I IFN-inducible genes during pregnancy is not associated with improved disease activity in pregnant patients with rheumatoid arthritis

During pregnancy, most patients with rheumatoid arthritis (RA) experience a spontaneous improvement in their condition. Since type I interferons (IFN) have immunomodulatory properties, we investigated whether type I IFN-inducible genes are upregulated in pregnant patients with RA. Peripheral blood mononuclear cells were evaluated using quantitative real-time polymerase chain reaction for type I IFN-inducible genes (IFI 35, IFI44, IFI44L, IFIT3, OAS1, and Siglec1) in patients with RA and healthy women during and after pregnancy as well as in nonpregnant controls. IFN-alpha and IFN-beta levels in sera of patients and healthy donors were analyzed by enzyme linked immunosorbent assay. It was found that healthy women did not show a change of gene expression levels from the second trimester until postpartum, yet some type I IFN-inducible genes were significantly upregulated in pregnant and postpartum women compared with nonpregnant individuals. In patients with RA, a pronounced upregulation of IFI35 and IFI44 at the second trimester and a peak expression of Siglec1 at the third trimester were observed. Pregnancy levels of IFI35 and IFI44 in patients with RA were higher than those of nonpregnant patients with RA. No significant association of gene expression levels with disease activity was found. In the sera of patients and healthy women, IFN-beta was undetectable and IFN-alpha levels remained stable throughout pregnancy and postpartum. Thus, pregnancy can give rise to an increased expression of type I IFN-inducible genes, reflecting an upregulation of the innate immune system. However, an association of type I IFN-inducible genes with pregnancy induced disease amelioration seems unlikely.

Gilbert syndrome and the development of antiretroviral therapy-associated hyperbilirubinemia

BACKGROUND: Unconjugated hyperbilirubinemia results from Gilbert syndrome and from antiretroviral therapy (ART) containing protease inhibitors. An understanding of the interaction between genetic predisposition and ART may help to identify individuals at highest risk for developing jaundice. METHODS: We quantified the contribution of UGT1A1*28 and ART to hyperbilirubinemia by longitudinally modeling 1386 total bilirubin levels in 96 human immunodeficiency virus (HIV)-infected individuals during a median of 6 years. RESULTS: The estimated average bilirubin level was 8.8 micromol/L (0.51 mg/dL). Atazanavir increased bilirubin levels by 15 mu mol/L (0.87 mg/dL), and indinavir increased bilirubin levels by 8 micromol/L (0.46 mg/dL). Ritonavir, lopinavir, saquinavir, and nelfinavir had no or minimal effect on bilirubin levels. Homozygous UGT1A1*28 increased bilirubin levels by 5.2 micromol/L (0.3 mg/dL). As a consequence, 67% of individuals homozygous for UGT1A1*28 and receiving atazanavir or indinavir had > or =2 episodes of hyperbilirubinemia in the jaundice range (>43 micromol/L [>2.5 mg/dL]), versus 7% of those with the common allele and not receiving either of those protease inhibitors (P<.001). Efavirenz resulted in decreased bilirubin levels, which is consistent with the induction of UDP-glucuronosyltransferase 1A1. CONCLUSIONS: Genotyping for UGT1A1*28 before initiation of ART would identify HIV-infected individuals at risk for hyperbilirubinemia and decrease episodes of jaundice.

Physiologic cold shock increases adherence of Moraxella catarrhalis to and secretion of interleukin 8 in human upper respiratory tract epithelial cells

Moraxella catarrhalis, a major nasopharyngeal pathogen of the human respiratory tract, is exposed to rapid and prolonged downshifts of environmental temperature when humans breathe cold air. In the present study, we show that a 26 degrees C cold shock up-regulates the expression of UspA1, a major adhesin and putative virulence factor of M. catarrhalis, by prolonging messenger RNA half-life. Cold shock promotes M. catarrhalis adherence to upper respiratory tract cells via enhanced binding to fibronectin, an extracellular matrix component that mediates bacterial attachment. Exposure of M. catarrhalis to 26 degrees C increases the outer membrane protein-mediated release of the proinflammatory cytokine interleukin 8 in pharyngeal epithelial cells. Furthermore, cold shock at 26 degrees C enhances the binding of salivary immunoglobulin A on the surface of M. catarrhalis. These data indicate that cold shock at a physiologically relevant temperature of 26 degrees C affects the nasopharyngeal host-pathogen interaction and may contribute to M. catarrhalis virulence.

Validation of the estimation of physiologic ability and surgical stress (E-PASS) score in liver surgery

BACKGROUND: The estimation of physiologic ability and surgical stress (E-PASS) has been used to produce a numerical estimate of expected mortality and morbidity after elective gastrointestinal surgery. The aim of this study was to validate E-PASS in a selected cohort of patients requiring liver resections (LR). METHODS: In this retrospective study, E-PASS predictor equations for morbidity and mortality were applied to the prospective data from 243 patients requiring LR. The observed rates were compared with predicted rates using Fisher's exact test. The discriminative capability of E-PASS was evaluated using receiver-operating characteristic (ROC) curve analysis. RESULTS: The observed and predicted overall mortality rates were both 3.3% and the morbidity rates were 31.3 and 26.9%, respectively. There was a significant difference in the comprehensive risk scores for deceased and surviving patients (p = 0.043). However, the scores for patients with or without complications were not significantly different (p = 0.120). Subsequent ROC curve analysis revealed a poor predictive accuracy for morbidity. CONCLUSIONS: The E-PASS score seems to effectively predict mortality in this specific group of patients but is a poor predictor of complications. A new modified logistic regression might be required for LR in order to better predict the postoperative outcome.

RNA-Seq-based analysis of the physiologic cold shock-induced changes in Moraxella catarrhalis gene expression

BACKGROUND Moraxella catarrhalis, a major nasopharyngeal pathogen of the human respiratory tract, is exposed to rapid downshifts of environmental temperature when humans breathe cold air. The prevalence of pharyngeal colonization and respiratory tract infections caused by M. catarrhalis is greatest in winter. We investigated how M. catarrhalis uses the physiologic exposure to cold air to regulate pivotal survival systems that may contribute to M. catarrhalis virulence. RESULTS In this study we used the RNA-seq techniques to quantitatively catalogue the transcriptome of M. catarrhalis exposed to a 26 °C cold shock or to continuous growth at 37 °C. Validation of RNA-seq data using quantitative RT-PCR analysis demonstrated the RNA-seq results to be highly reliable. We observed that a 26 °C cold shock induces the expression of genes that in other bacteria have been related to virulence a strong induction was observed for genes involved in high affinity phosphate transport and iron acquisition, indicating that M. catarrhalis makes a better use of both phosphate and iron resources after exposure to cold shock. We detected the induction of genes involved in nitrogen metabolism, as well as several outer membrane proteins, including ompA, m35-like porin and multidrug efflux pump (acrAB) indicating that M. catarrhalis remodels its membrane components in response to downshift of temperature. Furthermore, we demonstrate that a 26 °C cold shock enhances the induction of genes encoding the type IV pili that are essential for natural transformation, and increases the genetic competence of M. catarrhalis, which may facilitate the rapid spread and acquisition of novel virulence-associated genes. CONCLUSION Cold shock at a physiologically relevant temperature of 26 °C induces in M. catarrhalis a complex of adaptive mechanisms that could convey novel pathogenic functions and may contribute to enhanced colonization and virulence.

Physiologic and hematologic concerns of rotary blood pumps: what needs to be improved?

Over the past few decades, advances in ventricular assist device (VAD) technology have provided a promising therapeutic strategy to treat heart failure patients. Despite the improved performance and encouraging clinical outcomes of the new generation of VADs based on rotary blood pumps (RBPs), their physiologic and hematologic effects are controversial. Currently, clinically available RBPs run at constant speed, which results in limited control over cardiac workload and introduces blood flow with reduced pulsatility into the circulation. In this review, we first provide an update on the new challenges of mechanical circulatory support using rotary pumps including blood trauma, increased non-surgical bleeding rate, limited cardiac unloading, vascular malformations, end-organ function, and aortic valve insufficiency. Since the non-physiologic flow characteristic of these devices is one of the main subjects of scientific debate in the literature, we next emphasize the latest research regarding the development of a pulsatile RBP. Finally, we offer an outlook for future research in the field.