Predicting bacteremia in children with cancer and fever in chemotherapy-induced neutropenia: results of the prospective multicenter SPOG 2003 FN study

To develop a score predicting the risk of bacteremia in cancer patients with fever and neutropenia (FN), and to evaluate its performance.

The chitinase-like protein YKL-40 modulates cystic fibrosis lung disease

The chitinase-like protein YKL-40 was found to be increased in patients with severe asthma and chronic obstructive pulmonary disease (COPD), two disease conditions featuring neutrophilic infiltrates. Based on these studies and a previous report indicating that neutrophils secrete YKL-40, we hypothesized that YKL-40 plays a key role in cystic fibrosis (CF) lung disease, a prototypic neutrophilic disease. The aim of this study was (i) to analyze YKL-40 levels in human and murine CF lung disease and (ii) to investigate whether YKL-40 single-nucleotide polymorphisms (SNPs) modulate CF lung disease severity. YKL-40 protein levels were quantified in serum and sputum supernatants from CF patients and control individuals. Levels of the murine homologue BRP-39 were analyzed in airway fluids from CF-like βENaC-Tg mice. YKL-40SNPs were analyzed in CF patients. YKL-40 levels were increased in sputum supernatants and in serum from CF patients compared to healthy control individuals. Within CF patients, YKL-40 levels were higher in sputum than in serum. BRP-39 levels were increased in airways fluids from βENaC-Tg mice compared to wild-type littermates. In both CF patients and βENaC-Tg mice, YKL-40/BRP-39 airway levels correlated with the severity of pulmonary obstruction. Two YKL-40 SNPs (rs871799 and rs880633) were found to modulate age-adjusted lung function in CF patients. YKL-40/BRP-39 levelsare increased in human and murine CF airway fluids, correlate with pulmonary function and modulate CF lung disease severity genetically. These findings suggest YKL-40 as a potential biomarker in CF lung disease.

Long-term course of lung clearance index between infancy and school-age in cystic fibrosis subjects

Multiple breath washout (MBW) measurements have recently been shown to be sensitive for detection of early cystic fibrosis (CF) lung disease, with the lung clearance index (LCI) being the most common measure for ventilation inhomogeneity. The aim of this observational study was to describe the longitudinal course of LCI from time of clinical diagnosis during infancy to school-age in eleven children with CF. Elevated LCI during infancy was present in seven subjects, especially in those with later clinical diagnosis. Tracking of LCI at follow-up was evident only in the four most severe cases. We provide the first longitudinal data describing the long-term course of LCI in a small group of infants with CF. Our findings support the clinical usefulness of MBW measurements to detect and monitor early lung disease in children with CF already present shortly after clinical diagnosis.

Exposure to moderate air pollution during late pregnancy and cord blood cytokine secretion in healthy neonates

Background/Objectives Ambient air pollution can alter cytokine concentrations as shown in vitro and following short-term exposure to high air pollution levels in vivo. Exposure to pollution during late pregnancy has been shown to affect fetal lymphocytic immunophenotypes. However, effects of prenatal exposure to moderate levels of air pollutants on cytokine regulation in cord blood of healthy infants are unknown. Methods In a birth cohort of 265 healthy term-born neonates, we assessed maternal exposure to particles with an aerodynamic diameter of 10 µm or less (PM10), as well as to indoor air pollution during the last trimester, specifically the last 21, 14, 7, 3 and 1 days of pregnancy. As a proxy for traffic-related air pollution, we determined the distance of mothers' homes to major roads. We measured cytokine and chemokine levels (MCP-1, IL-6, IL-10, IL-1ß, TNF-α and GM-CSF) in cord blood serum using LUMINEX technology. Their association with pollution levels was assessed using regression analysis, adjusted for possible confounders. Results Mean (95%-CI) PM10 exposure for the last 7 days of pregnancy was 18.3 (10.3–38.4 µg/m3). PM10 exposure during the last 3 days of pregnancy was significantly associated with reduced IL-10 and during the last 3 months of pregnancy with increased IL-1ß levels in cord blood after adjustment for relevant confounders. Maternal smoking was associated with reduced IL-6 levels. For the other cytokines no association was found. Conclusions Our results suggest that even naturally occurring prenatal exposure to moderate amounts of indoor and outdoor air pollution may lead to changes in cord blood cytokine levels in a population based cohort.

Impact of sepsis on neurodevelopmental outcome in a Swiss National Cohort of extremely premature infants

Neonatal sepsis causes high mortality and morbidity in preterm infants, but less is known regarding the long-term outcome after sepsis. This study aimed to determine the impact of sepsis on neurodevelopment at 2 years' corrected age in extremely preterm infants.

Tidal volume single breath washout of two tracer gases--a practical and promising lung function test

Background Small airway disease frequently occurs in chronic lung diseases and may cause ventilation inhomogeneity (VI), which can be assessed by washout tests of inert tracer gas. Using two tracer gases with unequal molar mass (MM) and diffusivity increases specificity for VI in different lung zones. Currently washout tests are underutilised due to the time and effort required for measurements. The aim of this study was to develop and validate a simple technique for a new tidal single breath washout test (SBW) of sulfur hexafluoride (SF6) and helium (He) using an ultrasonic flowmeter (USFM). Methods The tracer gas mixture contained 5% SF6 and 26.3% He, had similar total MM as air, and was applied for a single tidal breath in 13 healthy adults. The USFM measured MM, which was then plotted against expired volume. USFM and mass spectrometer signals were compared in six subjects performing three SBW. Repeatability and reproducibility of SBW, i.e., area under the MM curve (AUC), were determined in seven subjects performing three SBW 24 hours apart. Results USFM reliably measured MM during all SBW tests (n = 60). MM from USFM reflected SF6 and He washout patterns measured by mass spectrometer. USFM signals were highly associated with mass spectrometer signals, e.g., for MM, linear regression r-squared was 0.98. Intra-subject coefficient of variation of AUC was 6.8%, and coefficient of repeatability was 11.8%. Conclusion The USFM accurately measured relative changes in SF6 and He washout. SBW tests were repeatable and reproducible in healthy adults. We have developed a fast, reliable, and straightforward USFM based SBW method, which provides valid information on SF6 and He washout patterns during tidal breathing.

Lung sequestration: a rare cause for pulmonary symptoms in adulthood

Lung sequestration is a rare congenital pulmonary disorder and is usually diagnosed in children with recurrent pulmonary infections. Lung sequestrations are not commonly found to be a cause of respiratory symptoms in adults.

Intermolecular Clamping by Hydrogen Bonds: 2-Pyridone center dot NH3

A combined spectroscopic and ab initio theoretical study of the doubly hydrogen-bonded complex of 2-pyridone (2PY) with NH3 has been performed. The S-1 <- S-0 spectrum extends up to approximate to 1200 cm(-1) above the 0(0)(0) band, close to twice the range observed for 2PY. The S-1 state nonradiative decay for vibrations above approximate to 300 cm(-1) in the NH3 complex is dramatically slowed down relative to bare 2PY. Also, the Delta v=2,4,... overtone bands of the v(1)' and v(2)' out-of-plane vibrations that dominate the low-energy spectral region of 2PY are much weaker or missing for 2PY center dot NH3, which implies that the bridging (2PY)NH center dot center dot center dot NH3 and H2NH center dot center dot center dot O=C H-bonds clamp the 2PY at a planar geometry in the S-1 state. The mass-resolved UV vibronic spectra of jet-cooled 2PY center dot NH3 and its H/D mixed isotopomers are measured using two-color resonant two-photon ionization spectroscopy. The S-0 and S-1 equilibrium structures and normal-mode frequencies are calculated by density functional (B3LYP) and correlated ab initio methods (MP2 and approximate second-order coupled-cluster, CC2). The S-1 <- S-0 vibronic assignments are based on configuration interaction singles (CIS) and CC2 calculations. A doubly H-bonded bridged structure of C-S symmetry is predicted, in agreement with that of Held and Pratt [J. Am. Chem. Soc. 1993, 115, 9718]. While the B3LYP and MP2 calculated rotational constants are in very good agreement with experiment, the calculated H2NH center dot center dot center dot O=C H-bond distance is approximate to 0.7 angstrom shorter than that derived by Held and Pratt. On the other hand, this underlines their observation that ammonia can act as a strong H-bond donor when built into an H-bonded bridge. The CC2 calculations predict the H2NH center dot center dot center dot O distance to increase by 0.2 angstrom upon S-1 <- S-0 electronic excitation, while the (2PY)NH center dot center dot center dot NH3 H-bond remains nearly unchanged. Thus, the expansion of the doubly H-bonded bridge in the excited state is asymmetric and almost wholly due to the weakening of the interaction of ammonia with the keto acceptor group.

Femtosecond Rotational Raman Coherence Spectroscopy of Cyclohexane in a Pulsed Supersonic Jet

We combine the technique of femtosecond degenerate four-wave mixing (fs-DFWM) with a high repetition-rate pulsed supersonic jet source to obtain the rotational coherence spectrum (RCS) of cold cyclohexane (C(6)H(12)) with high signal/noise ratio. In the jet expansion, the near-parallel flow pattern combined with rapid translational cooling effectively eliminate dephasing collisions, giving near-constant RCS signal intensities over time delays up to 5 ns. The vibrational cooling in the jet eliminates the thermally populated vibrations that complicate the RCS coherences of cyclohexane at room temperature [Bragger, G.; et al. J. Phys. Chem. A 2011, 115, 9567]. The rotational cooling reduces the high-J rotational-state population, yielding the most accurate ground-state rotational constant to date, B(0) = 4305.859(9) MHz. Based on this B(0), a reanalysis of previous room-temperature gas-cell RCS measurements of cydohexane gives improved vibration rotation interaction constants for the v(32), v(6), v(16), and v(24) vibrational states. Combining the experimental B(0)(C(6)H(12)) with CCSD(T) calculations yields a very accurate semiexperimental equilibrium structure of the chair isomer of cyclohexane

Cerebrospinal fluid hypocretin-1 levels during the active period of cluster headache

Hypocretins (orexins) are hypothalamic neuropeptides which are involved in a wide range of physiological processes in mammals including central pain processing. Genetic studies in humans evidenced a role for the hypocretinergic system in cluster headache (CH).