C-Reactive Protein and Hemogram Parameters for the Non-Sepsis Systemic Inflammatory Response Syndrome and Sepsis: What Do They Mean?

Objectives

Sepsis is one of the most common reasons of increased mortality and morbidity in the intensive care unit. The changes in CRP levels and hemogram parameters and their combinations may help to distinguish sepsis from non-sepsis SIRS. The aim of this study is to investigate the CRP and hemogram parameters as an indicator of sepsis.

Methods

A total of 2777 patients admitted to the ICU of two centers between 2006–2013 were evaluated retrospectively. The patients were diagnosed as SIRS (-), non-sepsis SIRS and sepsis. The patients who were under 18 years old, re-admitted, diagnosed with hematological disease, on corticosteroid and immunosuppressive therapy, SIRS (-), culture negative, undocumented laboratory values and outcomes were excluded. 1257 patients were divided into 2 groups as non-sepsis SIRS and sepsis. The patients’ demographic data, CRP levels, hemogram parameters, length of ICU stay and mortality were recorded.

Results

1257 patients were categorized as non-sepsis SIRS (816, 64.9%) and sepsis (441, 35.1%). In the multivariate analysis, the likelihood of sepsis was increased 3.2 (2.2–4.6), 1.7 (1.2–2.4), 1.6 (1.2–2.1), 2.3 (1.4–3.8), 1.5 (1.1–2.1) times by the APACHE II≥13, SOFA score≥4, CRP≥4.0, Lym_C<0.45 and PLT_C<150 respectively (p<0.001 p = 0.007 p = 0.004 p<0.001 p = 0.027). The likelihood of sepsis was increased 18.1 (8.4–38.7) times by the combination of CRP≥4.0, lym_C<0.45 and PLT_C<150 (P<0.001).

Conclusions

While WBC_C, Neu_C, Neu%, NLCR and Eo_C are far from being the indicators to distinguish sepsis from non-sepsis SIRS, the combinations of CRP, Lym_C and PLT_C can be used to determine the likelihood of sepsis.     

Risk sensitivity for amounts of and delay to rewards: adaptation for uncertainty or by-product of reward rate maximising?

Observations that humans and other species are sensitive to variability in the outcome of their choices has led to the widespread assumption that this sensitivity reflects adaptations to cope with risk (stochasticity of action consequences). We question this assumption in experiments with starlings. We show that choices between outcomes that are risky in both amount and delay to food are predictable from preferences in the absence of risk. We find that the overarching best predictor of an option's value is the average of the ratios of amount to delay across its (frequency weighted) outcomes, an expression known as “Expectation of the Ratios”, or EoR. Most tests of risk sensitivity focus on the predicted impact of energetic state on preference for risk. We show instead that under controlled state conditions subjects are variance- and risk-neutral with respect to EoR, and this implies variance neutrality for amounts and variance-proneness for delays. The weak risk aversion for amounts often reported requires a small modification of EoR. EoR is consistent with associative learning: acquisition of value for initially neutral stimuli is roughly proportional to the magnitude of their consequences and inversely proportional to the interval between the stimulus and its consequence's onset. If, as is likely, the effect of amount on acquisition is sublinear, the result is a deviation from EoR towards risk aversion for amount. In 3 experiments, we first establish individual birds’ preferences between pairs of fixed options that differ in both amount and delay (small-sooner vs. large-later), and then examine choices between stochastic mixtures that include these options. Experiment 1 uses a titration to establish certainty equivalents, while experiments 2 and 3 measure degree of preference between options with static parameters. The mixtures differ in the coefficient of variation of amount, delay, or both, but EoR is sufficient to predict all results, with no additional explanatory role for riskiness.     

Cell growth: downstream of Myc - to grow or to cycle?

For many years, Myc function has been linked to the control of cell-cycle progression. Now, increasing evidence shows that Myc also controls cell growth, and that these two processes are regulated independently.     

Protein microarrays: a chance to study microorganisms?

Within the last 5 years, protein microarrays have been developed and applied to multiple approaches: identification of protein–protein interactions or protein–small molecule interactions, cancer profiling, detection of microorganisms and toxins, and identification of antibodies due to allergens, autoantigens, and pathogens. Protein microarrays are small size (typically in the microscopy slide format) planar analytical devices with probes arranged in high density to provide the ability to screen several hundred to thousand known substrates (e.g., proteins, peptides, antibodies) simultaneously. Due to their small size, only minute amounts of spotted probes and analytes (e.g., serum) are needed; this is a particularly important feature, for these are limited or expensive. In this review, different types of protein microarrays are reviewed: protein microarrays (PMAs), with spotted proteins or peptides; antibody microarrays (AMAs), with spotted antibodies or antibody fragments (e.g., scFv); reverse phase protein microarrays (RPMAs), a special form of PMA where crude protein mixtures (e.g., cell lysates, fractions) are spotted; and nonprotein microarrays (NPMAs) where macromolecules other than proteins and nucleic acids (e.g., carbohydrates, monosaccharides, lipopolysaccharides) are spotted. In this study, exemplary experiments for all types of protein arrays are discussed wherever applicable with regard to investigations of microorganisms.     

Redundant or complementary? Impact of a colonizing species on community structure and function

Recent studies suggest that species with similar functional traits will have similar effects on ecosystems, but evidence for redundancy of species impacts is limited. Here we use a long‐term experiment to gain insight into functional relationships within a desert rodent community. Experimental removal of kangaroo rats, Dipodomys spp., coupled with the recent, serendipitous colonization of a single species of large pocket mouse Chaetodipus baileyi yielded treatments that differed in the diversity of large granivorous rodents present. We evaluated functional overlap of C. baileyi and the other resident large granivores (i.e. the kangaroo rats) by comparing total energy use of granivorous rodents and total abundance and species richness of small granivores across treatments before and after the arrival of C. baileyi. We found that C. baileyi almost completely compensated for the changes in these key ecosystem‐level properties caused by kangaroo rat removal, but it differentially impacted the population dynamics of individual small granivorous rodent species. Thus, its effects were largely complementary, rather than redundant, to those of the missing kangaroo rats. Although short‐term or single‐measure analyses may suggest redundancy, our results support the longstanding dictum that niches of coexisting species are often similar but rarely, if ever, identical.     

ψ-Constrained Simulations of Protein Folding Transition States: Implications for Calculating ?

ψ-analysis has been used to identify interresidue contacts in the transition state ensemble (TSE) of ubiquitin and other proteins. The magnitude of ψ depends on the degree to which an inserted bihistidine (biHis) metal ion binding site is formed in the TSE. A ψ equal to zero or one indicates that the biHis site is absent or fully native-like, respectively, while a fractional ψ implies that in the TSE, the biHis site recovers only part of the binding-induced stabilization of the native state. All-atom Langevin dynamics simulations of the TSE are performed with restrictions imposed only on the distances between the pairs of residues with experimentally determined ψ of unity. When a site with a fractional ψ lies adjacent to a site with ψ = 1, the fractional ψ generally signifies that the “fractional site” has a distorted geometry in the TSE. When a fractional site is distal to the sites with ψ = 1, however, the histidines sample configurations in which the site is absent. The simulations indicate that the ψ = 1 sites by themselves can be used to generate a well-defined TSE having near-native topology. ? values calculated from the TS simulations exhibit mixed agreement with the experimental values. The origin and implication of the disparities are discussed.     

Antiprion immunotherapy: to suppress or to stimulate?

Although human prion diseases are rare, they are invariably fatal, and treatments remain elusive. Hundreds of iatrogenic prion transmissions have occurred in the past two decades, and the bovine spongiform encephalopathy epidemic has raised concerns about prion transmission from cattle to humans. Research into therapeutics for prion disease is being pursued in several centres and prominently includes immunological strategies. Currently, the options that are being explored aim either to mobilize the innate and adaptive immune systems towards prion destruction or to suppress or dedifferentiate the lymphoreticular compartments that replicate prions. This article reviews the pathophysiology of prion diseases in mouse models and discusses their relevance to immunotherapeutic and immunoprophylactic antiprion strategies.     

Intermittent hypoxia: cause of or therapy for systemic hypertension?

During acute episodes of hypoxia, chemoreceptor-mediated sympathetic activity increases heart rate, cardiac output, peripheral resistance and systemic arterial pressure. However, different intermittent hypoxia paradigms produce remarkably divergent effects on systemic arterial pressure in the post-hypoxic steady state. The hypertensive effects of obstructive sleep apnea (OSA) vs. the depressor effects of therapeutic hypoxia exemplify this divergence. OSA, a condition afflicting 15-25% of American men and 5-10% of women, has been implicated in the pathogenesis of systemic hypertension and is a major risk factor for heart disease and stroke. OSA imposes a series of brief, intense episodes of hypoxia and hypercapnia, leading to persistent, maladaptive chemoreflex-mediated activation of the sympathetic nervous system which culminates in hypertension. Conversely, extensive evidence in animals and humans has shown controlled intermittent hypoxia conditioning programs to be safe, efficacious modalities for prevention and treatment of hypertension. This article reviews the pertinent literature in an attempt to reconcile the divergent effects of intermittent hypoxia therapy and obstructive sleep apnea on hypertension. Special emphasis is placed on research conducted in the nations of the former Soviet Union, where intermittent hypoxia conditioning programs are being applied therapeutically to treat hypertension in patients. Also reviewed is evidence regarding mechanisms of the pro- and anti-hypertensive effects of intermittent hypoxia.     

Inhibition of NETosis for treatment purposes: friend or foe?

Molecular and Cellular Biochemistry - Active neutrophils participate in innate and adaptive immune responses through various mechanisms, one of the most important of which is the formation and...     

Heterogeneity of depolymerized heparin SEC fractions: to pool or not to pool?

In the structural analysis of heparin and heparan sulfate, it is customary to combine or pool like-sized fractions obtained by size-exclusion chromatography (SEC) of enzymatically derived heparin oligosaccharides. In this study, we examine the heterogeneity of preparative-scale SEC fractions obtained from enzymatic digests of porcine intestinal mucosa heparin. Each fraction was profiled by capillary electrophoresis with UV detection (CE−UV) using a 60 mM formic acid running buffer at pH 3.43. Differences in the composition and relative concentration of components of the SEC fractions were observed for disaccharides and larger oligosaccharides. The heterogeneity of the fractions becomes more pronounced when heparin is digested using a heparin lyase cocktail. The heterogeneity of preparative SEC fractions was further investigated by reversed-phase ion-pairing ultraperformance liquid chromatography coupled with mass spectrometry (RPIP−UPLC−MS) using the ion-pairing reagent, tributylamine (Bu₃N). Our results suggest that preliminary profiling of preparative SEC fractions prior to pooling may simplify efforts to identify and/or isolate rare structures.     

Worm therapy: for or against?

This article succinctly reviews the weight of evidence supporting worm therapy, and asks the question whether the evidence is sufficient to support the use of parasitic worms as investigational medicinal products.     

The somatopause: to treat or not to treat?

There is much evidence that some aspects of ageing are similar to those observed in selective hormone deficiencies during adulthood. Replacement therapy in hypogonadism and/or growth hormone (GH) deficiency in adulthood is very successful in reversing the related clinical symptomatology. However, preliminary studies of GH treatment in the normal elderly have been largely disappointing: an increase in muscle mass is only accompanied by improved muscle strength if exercise is also increased during this period. No real benefit of GH therapy, additional to that of exercise, has been reported. Epidemiological studies indicate a relationship between high-normal insulin-like growth factor-I levels and cancer development. No definitive answers can presently be given regarding the safety of long-term GH therapy in otherwise healthy individuals during the somatopause.