Total Plasma Protein in Very Preterm Babies: Prognostic Value and Comparison with Illness Severity Scores

Objective

We aimed to investigate the predictive value for severe adverse outcome of plasma protein measurements on day one of life in very preterm infants and to compare total plasma protein levels with the validated illness severity scores CRIB, CRIB-II, SNAP-II and SNAPPE-II, regarding their predictive ability for severe adverse outcome.

Methods

We analyzed a cohort of infants born at 24–31 weeks gestation, admitted to the tertiary intensive care unit of a university hospital over 10.5 years. The outcome measure was “severe adverse outcome” defined as death before discharge or severe neurological injury on cranial ultrasound. The adjusted odd ratio (aOR) and 95% confidence interval (95% CI) of severe adverse outcome for hypoproteinemia (total plasma protein level <40 g/L) was calculated by univariate and multivariate analyses. Calibration (Hosmer-Lemeshow goodness-of-fit) was performed and the predictive ability for severe adverse outcome was assessed for total plasma protein and compared with CRIB, CRIB-II, SNAP-II and SNAPPE-II, by calculating receiver operating characteristic (ROC) curves and their associated area under the curve (AUC).

Results

761 infants were studied: 14.4% died and 4.1% survived with severe cerebral ultrasound findings. The aOR of severe adverse outcome for hypoproteinemia was 6.1 (95% CI 3.8–9.9). The rank order for variables, as assessed by AUCs and 95% CIs, in predicting outcome was: total plasma protein [0.849 (0.821–0.873)], SNAPPE-II [0.822 (0.792–0.848)], CRIB [0.821 (0.792–0.848)], SNAP-II [0.810 (0.780–0.837)] and CRIB-II [0.803 (0.772–0.830)]. Total plasma protein predicted severe adverse outcome significantly better than CRIB-II and SNAP-II (both p<0.05). Calibration for total plasma protein was very good.

Conclusions

Early hypoproteinemia has prognostic value for severe adverse outcome in very preterm, sick infants. Total plasma protein has a predictive performance comparable with CRIB and SNAPPE-II and greater than other validated severity scores.     

Neurotrophins are expressed in giant cell arteritis lesions and may contribute to vascular remodeling

Introduction

Giant cell arteritis (GCA) is characterized by intimal hyperplasia leading to ischaemic manifestations that involve large vessels. Neurotrophins (NTs) and their receptors (NTRs) are protein factors for growth, differentiation and survival of neurons. They are also involved in the migration of vascular smooth muscle cells (VSMCs). Our aim was to investigate whether NTs and NTRs are involved in vascular remodelling of GCA.

Methods

We included consecutive patients who underwent a temporal artery biopsy for suspected GCA. We developed an enzymatic digestion method to obtain VSMCs from smooth muscle cells in GCA patients and controls. Neurotrophin protein and gene expression and functional assays were studied from these VSMCs. Neurotrophin expression was also analysed by immunohistochemistry in GCA patients and controls.

Results

Whereas temporal arteries of both GCA patients (n = 22) and controls (n = 21) expressed nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB) and sortilin, immunostaining was more intense in GCA patients, especially in the media and intima, while neurotrophin-3 (NT-3) and P75 receptor (P75^NTR) were only detected in TA from GCA patients. Expression of TrkB, a BDNF receptor, was higher in GCA patients with ischaemic complications. Serum NGF was significantly higher in GCA patients (n = 28) vs. controls (n = 48), whereas no significant difference was found for BDNF and NT-3. NGF and BDNF enhanced GCA-derived temporal artery VSMC proliferation and BDNF facilitated migration of temporal artery VSMCs in patients with GCA compared to controls.

Conclusions

Our results suggest that NTs and NTRs are involved in vascular remodelling of GCA. In GCA-derived temporal artery VSMC, NGF promoted proliferation and BDNF enhanced migration by binding to TrkB and p75^NTR receptors. Further experiments are needed on a larger number of VSMC samples to confirm these results.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-014-0487-z) contains supplementary material, which is available to authorized users.     

Structure and dynamics of Mycobacterium tuberculosis truncated hemoglobin N: insights from NMR spectroscopy and molecular dynamics simulations

The potent nitric oxide dioxygenase (NOD) activity (trHbN-Fe2?-O? + (?)NO → trHbN-Fe3?-OH? + NO??) of Mycobacterium tuberculosis truncated hemoglobin N (trHbN) protects aerobic respiration from inhibition by (?)NO. The high activity of trHbN has been attributed in part to the presence of numerous short-lived hydrophobic cavities that allow partition and diffusion of the gaseous substrates (?)NO and O? to the active site. We investigated the relation between these cavities and the dynamics of the protein using solution NMR spectroscopy and molecular dynamics (MD). Results from both approaches indicate that the protein is mainly rigid with very limited motions of the backbone N-H bond vectors on the picoseconds-nanoseconds time scale, indicating that substrate diffusion and partition within trHbN may be controlled by side-chains movements. Model-free analysis also revealed the presence of slow motions (microseconds-milliseconds), not observed in MD simulations, for many residues located in helices B and G including the distal heme pocket Tyr33(B10). All currently known crystal structures and molecular dynamics data of truncated hemoglobins with the so-called pre-A N-terminal extension suggest a stable α-helical conformation that extends in solution. Moreover, a recent study attributed a crucial role to the pre-A helix for NOD activity. However, solution NMR data clearly show that in near-physiological conditions these residues do not adopt an α-helical conformation and are significantly disordered and that the helical conformation seen in crystal structures is likely induced by crystal contacts. Although this lack of order for the pre-A does not disagree with an important functional role for these residues, our data show that one should not assume an helical conformation for these residues in any functional interpretation. Moreover, future molecular dynamics simulations should not use an initial α-helical conformation for these residues in order to avoid a bias based on an erroneous initial structure for the N-termini residues. This work constitutes the first study of a truncated hemoglobin dynamics performed by solution heteronuclear relaxation NMR spectroscopy.     

Extraction of lipids and pigments of Chlorella vulgaris by supercritical carbon dioxide: influence of bead milling on extraction performance

The influence of bead milling on the extraction of lipids and pigments by supercritical carbon dioxide was investigated in this study. Different operating parameters for the 3-h process were first tested on raw Chlorella vulgaris; 600 bar was the optimum pressure at 60 °C with a carbon dioxide flow rate of 30 g min^?1. Under these operating conditions, 10 % of total lipid containing chlorophyll and carotenoids with 1.61 and 1.72 mg g^?1 dry weight of microalga, respectively, has been recovered. Microscopic observation was used to assess a cell wall breakage through bead milling, which produced positive results in terms of increasing the yield of biomolecules of interest. Thus, under the same operating conditions, the yield of total lipid extract, chlorophyll and carotenoids increased significantly. Moreover, the addition of a polar co-solvent to a raw microalga had a considerable effect on the final extract. Overall, the addition of 5 % w v^?1 ethanol to a raw microalga increased the total extract yield by 27 %, and bead milling increased the total extract yield by 16 %. Chlorophyll and carotenoids were also significantly affected by the addition of ethanol, with an 81 and 65 % increase with a raw microalga and a 61 and 52 % increase using bead milling, respectively.     

Commuter Mobility and the Spread of Infectious Diseases: Application to Influenza in France

Commuting data is increasingly used to describe population mobility in epidemic models. However, there is little evidence that the spatial spread of observed epidemics agrees with commuting. Here, using data from 25 epidemics for influenza-like illness in France (ILI) as seen by the Sentinelles network, we show that commuting volume is highly correlated with the spread of ILI. Next, we provide a systematic analysis of the spread of epidemics using commuting data in a mathematical model. We extract typical paths in the initial spread, related to the organization of the commuting network. These findings suggest that an alternative geographic distribution of GP accross France to the current one could be proposed. Finally, we show that change in commuting according to age (school or work commuting) impacts epidemic spread, and should be taken into account in realistic models.     

Infestation by the mite Harpirhynchus nidulans in the Bearded Tit Panurus biarmicus

Capsule Mites sometimes induced voluminous subcutaneous cysts in featherless parts.

Aims To describe the first reported infestation by the skin-dweller mite Harpirhynchus nidulans in Bearded Tits Panurus biarmicus and for the Timaliidae family, to detect possible fitness costs for the host and to determine the distribution of the parasite within the distribution range of the host.

Methods Parasites were identified using a microscope. Wing-length and body mass were recorded on both uninfected and infected birds captured at different times during the year. We also considered historical data, and contact was made with 32 European ringing stations to identify the distribution range of the parasite.

Results Subcutaneous reproduction of the mite Harpirhynchus nidulans induced the development of voluminous dermal nodules in Panurus biarmicus. There were no differences in body mass or wing-length with respect to infestation. In the south of France, prevalence changed from 10.6% in spring to 4.7% in autumn. Both sexes are equally parasitized. Occurrence of dermal cysts is reported from several southern European populations of Bearded Tits, whereas it seems to be absent from northern latitudes.

Conclusion The occurrence of a Harpirhynchus mite in wild bird populations is reported for the first time. We consider aspects of its biology, host–parasite system, host-specificity, co-adaptation of the mite reproductive cycle to the social dynamics of its host and metapopulational host–parasite dynamics.     

Verification and comparison of four numerical schemes for a 1D viscoelastic blood flow model

A reliable and fast numerical scheme is crucial for the 1D simulation of blood flow in compliant vessels. In this paper, a 1D blood flow model is incorporated with a Kelvin–Voigt viscoelastic arterial wall. This leads to a nonlinear hyperbolic–parabolic system, which is then solved with four numerical schemes, namely: MacCormack, Taylor–Galerkin, monotonic upwind scheme for conservation law and local discontinuous Galerkin. The numerical schemes are tested on a single vessel, a simple bifurcation and a network with 55 arteries. The numerical solutions are checked favorably against analytical, semi-analytical solutions or clinical observations. Among the numerical schemes, comparisons are made in four important aspects: accuracy, ability to capture shock-like phenomena, computational speed and implementation complexity. The suitable conditions for the application of each scheme are discussed.