Free energies, vacancy concentrations and density distribution anisotropies in hard--sphere crystals: A combined density functional and simulation study

We perform a comparative study of the free energies and the density distributions in hard sphere crystals using Monte Carlo simulations and density functional theory (employing Fundamental Measure functionals). Using a recently introduced technique (Schilling and Schmid, J. Chem. Phys 131, 231102 (2009)) we obtain crystal free energies to a high precision. The free energies from Fundamental Measure theory are in good agreement with the simulation results and demonstrate the applicability of these functionals to the treatment of other problems involving crystallization. The agreement between FMT and simulations on the level of the free energies is also reflected in the density distributions around single lattice sites. Overall, the peak widths and anisotropy signs for different lattice directions agree, however, it is found that Fundamental Measure theory gives slightly narrower peaks with more anisotropy than seen in the simulations. Among the three types of Fundamental Measure functionals studied, only the White Bear II functional (Hansen-Goos and Roth, J. Phys.: Condens. Matter 18, 8413 (2006)) exhibits sensible results for the equilibrium vacancy concentration and a physical behavior of the chemical potential in crystals constrained by a fixed vacancy concentration.Comment: 17 pages, submitted to Phys. Rev.

The current state of hospital-based emergency medicine in Germany

Germany has a long tradition of having physicians, often anesthesiologists with additional training in emergency medicine, deliver prehospital emergency care. Hospital-based emergency medicine in Germany also differs significantly from the Anglo-American model, and until recently having separate emergency rooms for different departments was the norm. In the past decade, many hospitals have created “centralized emergency departments” [Zentrale Notaufnahme (ZNAs)]. There is ongoing debate about the training and certification of physicians working in the ZNAs and whether Germany will adopt a specialty board certification for emergency medicine

Astrocyte-to-neuron communication through integrin-engaged Thy-1/CBP/Csk/Src complex triggers neurite retraction via the RhoA/ROCK pathway.

Two key proteins for cellular communication between astrocytes and neurons are αvβ3 integrin and the receptor Thy-1. Binding of these molecules in the same (cis) or on adjacent (trans) cellular membranes induces Thy-1 clustering, triggering actin cytoskeleton remodeling. Molecular events that could explain how the Thy-1-αvβ3 integrin interaction signals have only been studied separately in different cell types, and the detailed transcellular communication and signal transduction pathways involved in neuronal cytoskeleton remodeling remain unresolved. Using biochemical and genetic approaches, single-molecule tracking, and high-resolution nanoscopy, we provide evidence that upon binding to αvβ3 integrin, Thy-1 mobility decreased while Thy-1 nanocluster size increased. This occurred concomitantly with inactivation and exclusion of the non-receptor tyrosine kinase Src from the Thy-1/C-terminal Src kinase (Csk)-binding protein (CBP)/Csk complex. The Src inactivation decreased the p190Rho GTPase activating protein phosphorylation, promoting RhoA activation, cofilin, and myosin light chain II phosphorylation and, consequently, neurite shortening. Finally, silencing the adaptor CBP demonstrated that this protein was a key transducer in the Thy-1 signaling cascade. In conclusion, these data support the hypothesis that the Thy-1-CBP-Csk-Src-RhoA-ROCK axis transmitted signals from astrocytic integrin-engaged Thy-1 (trans) to the neuronal actin cytoskeleton. Importantly, the β3 integrin in neurons (cis) was not found to be crucial for neurite shortening. This is the first study to detail the signaling pathway triggered by αvβ3, the endogenous Thy-1 ligand, highlighting the role of membrane-bound integrins as trans acting ligands in astrocyte-neuron communication

Ratiometric high-resolution imaging of JC-1 fluorescence reveals the subcellular heterogeneity of astrocytic mitochondria

Using the mitochondrial potential (ΔΨm) marker JC-1 (5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolylcarbocyanine iodide) and high-resolution imaging, we functionally analyzed mitochondria in cultured rat hippocampal astrocytes. Ratiometric detection of JC-1 fluorescence identified mitochondria with high and low ΔΨm. Mitochondrial density was highest in the perinuclear region, whereas ΔΨm tended to be higher in peripheral mitochondria. Spontaneous ΔΨm fluctuations, representing episodes of increased energization, appeared in individual mitochondria or synchronized in mitochondrial clusters. They continued upon withdrawal of extracellular Ca2+, but were antagonized by dantrolene or 2-aminoethoxydiphenylborate (2-APB). Fluo-3 imaging revealed local cytosolic Ca2+ transients with similar kinetics that also were depressed by dantrolene and 2-APB. Massive cellular Ca2+ load or metabolic impairment abolished ΔΨm fluctuations, occasionally evoking heterogeneous mitochondrial depolarizations. The detected diversity and ΔΨm heterogeneity of mitochondria confirms that even in less structurally polarized cells, such as astrocytes, specialized mitochondrial subpopulations coexist. We conclude that ΔΨm fluctuations are an indication of mitochondrial viability and are triggered by local Ca2+ release from the endoplasmic reticulum. This spatially confined organelle crosstalk contributes to the functional heterogeneity of mitochondria and may serve to adapt the metabolism of glial cells to the activity and metabolic demand of complex neuronal networks. The established ratiometric JC-1 imaging—especially combined with two-photon microscopy—enables quantitative functional analyses of individual mitochondria as well as the comparison of mitochondrial heterogeneity in different preparations and/or treatment conditions

Epidemic Microclusters of Blood-Culture Proven Sepsis in Very-Low-Birth Weight Infants: Experience of the German Neonatal Network

INTRODUCTION: We evaluated blood culture-proven sepsis episodes occurring in microclusters in very-low-birth-weight infants born in the German Neonatal Network (GNN) during 2009-2010. METHODS: Thirty-seven centers participated in GNN; 23 centers enrolled ≥50 VLBW infants in the study period. Data quality was approved by on-site monitoring. Microclusters of sepsis were defined as occurrence of at least two blood-culture proven sepsis events in different patients of one center within 3 months with the same bacterial species. For microcluster analysis, we selected sepsis episodes with typically cross-transmitted bacteria of high clinical significance including gram-negative rods and Enterococcus spp. RESULTS: In our cohort, 12/2110 (0.6%) infants were documented with an early-onset sepsis and 235 late-onset sepsis episodes (≥72 h of age) occurred in 203/2110 (9.6%) VLBW infants. In 182/235 (77.4%) late-onset sepsis episodes gram-positive bacteria were documented, while coagulase negative staphylococci were found to be the most predominant pathogens (48.5%, 95%CI: 42.01-55.01). Candida spp. and gram-negative bacilli caused 10/235 (4.3%, 95%CI: 1.68% -6.83%) and 43/235 (18.5%) late-onset sepsis episodes, respectively. Eleven microclusters of blood-culture proven sepsis were detected in 7 hospitals involving a total 26 infants. 16/26 cluster patients suffered from Klebsiella spp. sepsis. The median time interval between the first patient's Klebsiella spp. sepsis and cluster cases was 14.1 days (interquartile range: 1-27 days). First patients in the cluster, their linked cases and sporadic sepsis events did not show significant differences in short term outcome parameters. DISCUSSION: Microclusters of infection are an important phenomenon for late-onset sepsis. Most gram-negative cluster infections occur within 30 days after the first patient was diagnosed and Klebsiella spp. play a major role. It is essential to monitor epidemic microclusters of sepsis in surveillance networks to adapt clinical practice, inform policy and further improve quality of care

Homeopathic treatment of patients with chronic sinusitis: A prospective observational study with 8 years follow-up

<p>Abstract</p> <p>Background</p> <p>An evaluation of homeopathic treatment and the outcomes in patients suffering from sinusitis for ≥12 weeks in a usual care situation.</p> <p>Methods</p> <p>Subgroup analysis including all patients with chronic sinusitis (ICD-9: 473.9; ≥12 weeks duration) of a large prospective multicentre observational study population. Consecutive patients presenting for homeopathic treatment were followed-up for 2 years, and complaint severity, health-related quality of life (QoL), and medication use were regularly recorded. We also present here patient-reported health status 8 years post initial treatment.</p> <p>Results</p> <p>The study included 134 adults (mean age 39.8 ± 10.4 years, 76.1% women), treated by 62 physicians. Patients had suffered from chronic sinusitis for 10.7 ± 9.8 years. Almost all patients (97.0%) had previously been treated with conventional medicine. For sinusitis, effect size (effect divided by standard deviation at baseline) of complaint severity was 1.58 (95% CI 1.77; 1.40), 2.15 (2.38; 1.92), and 2.43 (2.68; 2.18) at 3, 12, and 24 months respectively. QoL improved accordingly, with SF-36 changes in physical component score 0.27 (0.15; 0.39), 0.35 (0.19; 0.52), 0.44 (0.23; 0.65) and mental component score 0.66 (0.49; 0.84), 0.71 (0.50; 0.92), 0.65 (0.39; 0.92), 0.74 (0.49; 1.00) at these points. The effects were still present after 8 years with SF-36 physical component score 0.38 (0.10; 0.65) and mental component score 0.74 (0.49; 1.00).</p> <p>Conclusion</p> <p>This observational study showed relevant improvements that persisted for 8 years in patients seeking homeopathic treatment because of sinusitis. The extent to which the observed effects are due to the life-style regulation and placebo or context effects associated with the treatment needs clarification in future explanatory studies.</p

Caveolin-1-Enhanced Motility and Focal Adhesion Turnover Require Tyrosine-14 but Not Accumulation to the Rear in Metastatic Cancer Cells

Caveolin-1 is known to promote cell migration, and increased caveolin-1 expression is associated with tumor progression and metastasis. In fibroblasts, caveolin-1 polarization and phosphorylation of tyrosine-14 are essential to promote migration. However, the role of caveolin-1 in migration of metastatic cells remains poorly defined. Here, caveolin-1 participation in metastatic cell migration was evaluated by shRNA targeting of endogenous caveolin-1 in MDA-MB-231 human breast cancer cells and ectopic expression in B16-F10 mouse melanoma cells. Depletion of caveolin-1 in MDA-MB-231 cells reduced, while expression in B16-F10 cells promoted migration, polarization and focal adhesion turnover in a sequence of events that involved phosphorylation of tyrosine-14 and Rac-1 activation. In B16-F10 cells, expression of a non-phosphorylatable tyrosine-14 to phenylalanine mutant failed to recapitulate the effects observed with wild-type caveolin-1. Alternatively, treatment of MDA-MB-231 cells with the Src family kinase inhibitor PP2 reduced caveolin-1 phosphorylation on tyrosine-14 and cell migration. Surprisingly, unlike for fibroblasts, caveolin-1 polarization and re-localization to the trailing edge were not observed in migrating metastatic cells. Thus, expression and phosphorylation, but not polarization of caveolin-1 favor the highly mobile phenotype of metastatic cells