Failure of neutrophil migration toward infectious focus in severe sepsis: a critical event for the outcome of this syndrome

Sepsis is a systemic inflammatory response commonly caused by bacterial infection. We demonstrated that the outcome of sepsis induced by cecal ligation and puncture (CLP) correlates with the severity of the neutrophil migration failure towards infectious focus. Failure appears to be due to a decrease in the rolling and adhesion of neutrophil to endothelium cells. It seems that neutrophil migration impairment is mediated by the circulating inflammatory cytokines, such as TNF-alpha and IL-8, which induce the nitric oxide (NO) production systemically. It is supported by the fact that intravenous administration of these cytokines reduces the neutrophil migration induced by different inflammatory stimuli, and in severe sepsis the circulating concentrations of the cytokines and chemokines are significantly increased. Moreover, the neutrophil migration failure and the reduction in the rolling/adhesion were not observed in iNOS-/- mice and, aminoguanidine prevented this event. We also demonstrated that the failure of neutrophil migration is a Toll-4 receptor (TLR4) dependent mechanism, since it was not observed in TLR4 deficient mice. Furthermore, it was also observed that circulating neutrophils obtained from septic patients present failure of neutrophil chemotaxis toward fMLP, IL-8, and LTB4 and an increased in sera concentrations of NO3 and cytokines. In conclusion, we demonstrated that, in sepsis, failure of neutrophil migration is critical for the outcome and that NO is involved in the process.

A study of governance practices in corporate foundations

Implementation of social investments through corporate foundations is growing and, therefore, it is important to study their governance aspects better. Governance is conceptualized as a set of control and incentive mechanisms to overcome the so-called agency conflicts, which originate from the separation of property and management in for-profit organizations, a concept also applied to nonprofit institutions. It is argued that corporate foundations have the characteristics both of companies and of civil society organizations, which distinguishes them from both types of organizations. This paper analyses a study in which a set of governance mechanisms, adapted from those identified by a literature review of corporate and nonprofit governance, was selected for study. It is an exploratory descriptive case study, which analyzed data about eight organizations collected through publications and interviews with their CEOs. The data analysis indicates that it is appropriate to distinguish the different organization types and to apply the agency theory. Research results indicate that the selected governance mechanisms may be adapted and used in corporate foundations. However, they are only partially applied in the observed cases, which suggests the need for further studies that might consolidate these practices in such organizations.

Effect of investments on fundamentals and market reaction on pre-operational and operational Brazilian companies for the period 2006-2012

ABSTRACT This paper provides evidence on the market reaction to corporate investment decisions whose shareholder value is largely attributed to growth options. The exploratory research raised pre-operational companies and their operational pairs on the same economy segments. It had the purpose of investigating the existence of statistical differentiation from financial indicators that reflect the installed assets and growth assets, and then study the market reaction to changes in fixed assets as a signaling element about investment decisions. The formation process of operational assets and shareholder value almost exclusively dependent on asset growth stands out in the pre-operational companies. As a result, differentiation tests confirmed that the pre-operational companies had their value especially derived on growth options. The market reaction was particularly bigger in pre-operational companies with abnormal negative stock returns, while the operational companies had positive returns, which may indicate that the quality of the investment is judged based on the financial disclosure. Additionally, operational companies' investors await the disclosure to adjust their prices. We conclude that the results are consistent with the empirical evidence and the participants in financial markets to long-term capital formation investments should give that special attention.

A comparative analysis of preprocessing techniques of cardiac event series for the study of heart rhythm variability using simulated signals

In the present study, using noise-free simulated signals, we performed a comparative examination of several preprocessing techniques that are used to transform the cardiac event series in a regularly sampled time series, appropriate for spectral analysis of heart rhythm variability (HRV). First, a group of noise-free simulated point event series, which represents a time series of heartbeats, was generated by an integral pulse frequency modulation model. In order to evaluate the performance of the preprocessing methods, the differences between the spectra of the preprocessed simulated signals and the true spectrum (spectrum of the model input modulating signals) were surveyed by visual analysis and by contrasting merit indices. It is desired that estimated spectra match the true spectrum as close as possible, showing a minimum of harmonic components and other artifacts. The merit indices proposed to quantify these mismatches were the leakage rate, defined as a measure of leakage components (located outside some narrow windows centered at frequencies of model input modulating signals) with respect to the whole spectral components, and the numbers of leakage components with amplitudes greater than 1%, 5% and 10% of the total spectral components. Our data, obtained from a noise-free simulation, indicate that the utilization of heart rate values instead of heart period values in the derivation of signals representative of heart rhythm results in more accurate spectra. Furthermore, our data support the efficiency of the widely used preprocessing technique based on the convolution of inverse interval function values with a rectangular window, and suggest the preprocessing technique based on a cubic polynomial interpolation of inverse interval function values and succeeding spectral analysis as another efficient and fast method for the analysis of HRV signals

Statistical analysis of event-related potential elicited by verb-complement merge in Brazilian Portuguese

An interesting fact about language cognition is that stimulation involving incongruence in the merge operation between verb and complement has often been related to a negative event-related potential (ERP) of augmented amplitude and latency of ca. 400 ms - the N400. Using an automatic ERP latency and amplitude estimator to facilitate the recognition of waves with a low signal-to-noise ratio, the objective of the present study was to study the N400 statistically in 24 volunteers. Stimulation consisted of 80 experimental sentences (40 congruous and 40 incongruous), generated in Brazilian Portuguese, involving two distinct local verb-argument combinations (nominal object and pronominal object series). For each volunteer, the EEG was simultaneously acquired at 20 derivations, topographically localized according to the 10-20 International System. A computerized routine for automatic N400-peak marking (based on the ascendant zero-cross of the first waveform derivative) was applied to the estimated individual ERP waveform for congruous and incongruous sentences in both series for all ERP topographic derivations. Peak-to-peak N400 amplitude was significantly augmented (P < 0.05; one-sided Wilcoxon signed-rank test) due to incongruence in derivations F3, T3, C3, Cz, T5, P3, Pz, and P4 for nominal object series and in P3, Pz and P4 for pronominal object series. The results also indicated high inter-individual variability in ERP waveforms, suggesting that the usual procedure of grand averaging might not be considered a generally adequate approach. Hence, signal processing statistical techniques should be applied in neurolinguistic ERP studies allowing waveform analysis with low signal-to-noise ratio.

The corporate bias and the molding of prescription practices: the case of hypertension

Drug management of hypertension has been a noticeable example of the influence of the pharmaceutical industry on prescription practices. The worldwide leading brands of blood pressure-lowering agents are angiotensin receptor-blocking agents, although they are considered to be simply substitutes of angiotensin-converting enzyme (ACE) inhibitors. Commercial strategies have been based on the results of clinical trials sponsored by drug companies. Most of them presented distortions in their planning, presentation or interpretation that favored the drugs from the sponsor, i.e., corporate bias. Atenolol, an ineffective blood pressure agent in elderly individuals, was the comparator drug in several trials. In a re-analysis of the INSIGHT trial, deaths appeared to have been counted twice. The LIFE trial appears in the title of more than 120 reproductions of the main and flawed trial, as a massive strategy of scientific marketing. Most guidelines have incorporated the corporate bias from the original studies, and the evidence from better designed studies, such as the ALLHAT trial, have been largely ignored. In trials published recently corporate influences have touched on ethical limits. In the ADVANCE trial, elderly patients with type 2 diabetes and cardiovascular disease or risk factors, allocated to placebo, were not allowed to use diuretic and full doses of an ACE inhibitor, despite the sound evidence of benefit demonstrated in previous trials. As a consequence, they had a 14% higher mortality rate than the participants allocated to the active treatment arm. This reality should be modified immediately, and a greater independence of the academy from the pharmaceutical industry is necessary.

Highly sensitive C-reactive protein and male gender are independently related to the severity of coronary disease in patients with metabolic syndrome and an acute coronary event

Patients with metabolic syndrome are at high-risk for development of atherosclerosis and cardiovascular events. The objective of this study was to examine the major determinants of coronary disease severity, including those coronary risk factors associated with metabolic syndrome, during the early period after an acute coronary episode. We tested the hypothesis that inflammatory markers, especially highly sensitive C-reactive protein (hsCRP), are related to coronary atherosclerosis, in addition to traditional coronary risk factors. Subjects of both genders aged 30 to 75 years (N = 116) were prospectively included if they had suffered a recent acute coronary syndrome (acute myocardial infarction or unstable angina pectoris requiring hospitalization) and if they had metabolic syndrome diagnosed according to the National Cholesterol Education Program/Adult Treatment Panel III. Patients were submitted to a coronary angiography and the burden of atherosclerosis was estimated by the Gensini score. The severity of coronary disease was correlated (Spearman’s or Pearson’s coefficient) with gender (r = 0.291, P = 0.008), age (r = 0.218, P = 0.048), hsCRP (r = 0.256, P = 0.020), ApoB/ApoA ratio (r = 0.233, P = 0.041), and carotid intima-media thickness (r = 0.236, P = 0.041). After multiple linear regression, only male gender (P = 0.046) and hsCRP (P = 0.012) remained independently associated with the Gensini score. In this high-risk population, male gender and high levels of hsCRP, two variables that can be easily obtained, were associated with more extensive coronary disease, identifying patients with the highest potential of developing new coronary events.

Attentional bias modulation by reappraisal in patients with generalized anxiety disorder: an event-related potential study

Affective states influence subsequent attention allocation. We evaluated emotional negativity bias modulation by reappraisal in patients with generalized anxiety disorder (GAD) relative to normal controls. Event-related potential (ERP) recordings were obtained, and changes in P200 and P300 amplitudes in response to negative or neutral words were noted after decreasing negative emotion or establishing a neutral condition. We found that in GAD patients only, the mean P200 amplitude after negative word presentation was much higher than after the presentation of neutral words. In normal controls, after downregulation of negative emotion, the mean P300 amplitude in response to negative words was much lower than after neutral words, and this was significant in both the left and right regions. In GAD patients, the negative bias remained prominent and was not affected by reappraisal at the early stage. Reappraisal was observed to have a lateralized effect at the late stage.