IL-6 predicts organ dysfunction and mortality in patients with multiple injuries

<p>Abstract</p> <p>Background</p> <p>Although therapeutic concepts of patients with major trauma have improved during recent years, organ dysfunction still remains a frequent complication during clinical course in intensive care units. It has previously been shown that cytokines are upregulated under stress conditions such as trauma or sepsis. However, it is still debatable if cytokines are adequate parameters to describe the current state of trauma patients. To elucidate the relevance of cytokines, we investigated if cytokines predict development of multiple organ dysfunction syndrome (MODS) or outcome.</p> <p>Methods</p> <p>A total of 143 patients with an injury severity score ≥ 16, between 16 and 65 years, admitted to the Hannover Medical School Level 1 Trauma Center between January 1997 and December 2001 were prospectively included in this study. Marshall Score for MODS was calculated for at least 14 days and plasma levels of TNF-α, IL-1β, IL-6, IL-8 and IL-10 were measured. To determine the association between cytokine levels and development of MODS the Spearman rank correlation coefficient was calculated and logistic regression and analysis were performed.</p> <p>Results and Discussion</p> <p>Patients with MODS had increased plasma levels of IL-6, IL-8 and IL-10. IL-6 predicted development of MODS with an overall accuracy of 84.7% (specificity: 98.3%, sensitivity: 16.7%). The threshold value for development of MODS was 761.7 pg/ml and 2176.0 pg/ml for mortality during the in patient time.</p> <p>Conclusion</p> <p>We conclude that plasma IL-6 levels predict mortality and that they are a useful tool to identify patients who are at risk for development of MODS.</p

Differential responses of ammonia-oxidizing archaea and bacteria to long-term fertilization in a New England salt marsh

© The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Frontiers in Aquatic Microbiology 3 (2013): 445, doi:10.3389/fmicb.2012.00445.Since the discovery of ammonia-oxidizing archaea (AOA), new questions have arisen about population and community dynamics and potential interactions between AOA and ammonia-oxidizing bacteria (AOB). We investigated the effects of long-term fertilization on AOA and AOB in the Great Sippewissett Marsh, Falmouth, MA, USA to address some of these questions. Sediment samples were collected from low and high marsh habitats in July 2009 from replicate plots that received low (LF), high (HF), and extra high (XF) levels of a mixed NPK fertilizer biweekly during the growing season since 1974. Additional untreated plots were included as controls (C). Terminal restriction fragment length polymorphism analysis of the amoA genes revealed distinct shifts in AOB communities related to fertilization treatment, but the response patterns of AOA were less consistent. Four AOB operational taxonomic units (OTUs) predictably and significantly responded to fertilization, but only one AOA OTU showed a significant pattern. Betaproteobacterial amoA gene sequences within the Nitrosospira-like cluster dominated at C and LF sites, while sequences related to Nitrosomonas spp. dominated at HF and XF sites. We identified some clusters of AOA sequences recovered primarily from high fertilization regimes, but other clusters consisted of sequences recovered from all fertilization treatments, suggesting greater physiological diversity. Surprisingly, fertilization appeared to have little impact on abundance of AOA or AOB. In summary, our data reveal striking patterns for AOA and AOB in response to long-term fertilization, and also suggest a missing link between community composition and abundance and nitrogen processing in the marsh.This work was supported in part by the National Science Foundation award DEB-0814586 (to Anne E. Bernhard). Additional support was provided by the George and Carol Milne Endowment at Connecticut College

Effects of Electronic Correlations on the Thermoelectric Power of the Cuprates

We show that important anomalous features of the normal-state thermoelectric power S of high-Tc materials can be understood as being caused by doping dependent short-range antiferromagnetic correlations. The theory is based on the fluctuation-exchange approximation applied to Hubbard model in the framework of the Kubo formalism. Firstly, the characteristic maximum of S as function of temperature can be explained by the anomalous momentum dependence of the single-particle scattering rate. Secondly, we discuss the role of the actual Fermi surface shape for the occurrence of a sign change of S as a function of temperature and doping.Comment: 4 pages, with eps figure

Targeting of Magnetic Nanoparticle-coated Microbubbles to the Vascular Wall Empowers Site-specific Lentiviral Gene Delivery in vivo

In the field of vascular gene therapy, targeting systems are promising advancements to improve site-specificity of gene delivery. Here, we studied whether incorporation of magnetic nanoparticles (MNP) with different magnetic properties into ultrasound sensitive microbubbles may represent an efficient way to enable gene targeting in the vascular system after systemic application. Thus, we associated novel silicon oxide-coated magnetic nanoparticle containing microbubbles (SO-Mag MMB) with lentiviral particles carrying therapeutic genes and determined their physico-chemical as well as biological properties compared to MMB coated with polyethylenimine-coated magnetic nanoparticles (PEI-Mag MMB). While there were no differences between both MMB types concerning size and lentivirus binding, SO-Mag MMB exhibited superior characteristics regarding magnetic moment, magnetizability as well as transduction efficiency under static and flow conditions in vitro. Focal disruption of lentiviral SO-Mag MMB by ultrasound within isolated vessels exposed to an external magnetic field decisively improved localized VEGF expression in aortic endothelium ex vivo and enhanced the angiogenic response. Using the same system in vivo, we achieved a highly effective, site-specific lentiviral transgene expression in microvessels of the mouse dorsal skin after arterial injection. Thus, we established a novel lentiviral MMB technique, which has great potential towards site-directed vascular gene therapy

Behavior of the thermopower in amorphous materials at the metal-insulator transition

Published versio

Loss-of-function variants in the KCNQ5 gene are implicated in genetic generalized epilepsies

Summary Background De novo missense variants in KCNQ5, encoding the voltage-gated K+ channel KV7.5, have been described to cause developmental and epileptic encephalopathy (DEE) or intellectual disability (ID). We set out to identify disease-related KCNQ5 variants in genetic generalized epilepsy (GGE) and their underlying mechanisms. Methods 1292 families with GGE were studied by next-generation sequencing. Whole-cell patch-clamp recordings, biotinylation and phospholipid overlay assays were performed in mammalian cells combined with homology modelling. Findings We identified three deleterious heterozygous missense variants, one truncation and one splice site alteration in five independent families with GGE with predominant absence seizures; two variants were also associated with mild to moderate ID. All missense variants displayed a strongly decreased current density indicating a loss-of-function (LOF). When mutant channels were co-expressed with wild-type (WT) KV7.5 or KV7.5 and KV7.3 channels, three variants also revealed a significant dominant-negative effect on WT channels. Other gating parameters were unchanged. Biotinylation assays indicated a normal surface expression of the variants. The R359C variant altered PI(4,5)P2-interaction. Interpretation Our study identified deleterious KCNQ5 variants in GGE, partially combined with mild to moderate ID. The disease mechanism is a LOF partially with dominant-negative effects through functional deficits. LOF of KV7.5 channels will reduce the M-current, likely resulting in increased excitability of KV7.5-expressing neurons. Further studies on network level are necessary to understand which circuits are affected and how this induces generalized seizures. Funding DFG/FNR Research Unit FOR-2715 (Germany/Luxemburg), BMBF rare disease network Treat-ION (Germany), foundation ‘no epilep’ (Germany)

Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A

Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures. Several rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A, which encodes a brain-expressed sodium channel subunit targeted by many anti-epileptic drugs. We undertook a genome-wide association study in 1018 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 7552 control subjects, with validation in an independent sample set comprising 959 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 3591 control subjects. To dissect out variants related to a history of febrile seizures, we tested cases with mesial temporal lobe epilepsy with hippocampal sclerosis with (overall n = 757) and without (overall n = 803) a history of febrile seizures. Meta-analysis revealed a genome-wide significant association for mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures at the sodium channel gene cluster on chromosome 2q24.3 [rs7587026, within an intron of the SCN1A gene, P = 3.36 × 10−9, odds ratio (A) = 1.42, 95% confidence interval: 1.26-1.59]. In a cohort of 172 individuals with febrile seizures, who did not develop epilepsy during prospective follow-up to age 13 years, and 6456 controls, no association was found for rs7587026 and febrile seizures. These findings suggest SCN1A involvement in a common epilepsy syndrome, give new direction to biological understanding of mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures, and open avenues for investigation of prognostic factors and possible prevention of epilepsy in some children with febrile seizure

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Fundstellen, Siedlungen und Naturräume als historische Quellen von der Urgeschichte bis zum Ende des ersten Jahrtausends n. Chr.

Fundstellen, Siedlungen und Naturräume als historische Quellen von der Urgeschichte bis zum Ende des ersten Jahrtausends n. Chr. : Regionalforschung am Beisp. d. Ostalbkreises. - 2 Bde. - 1995. - 137, 316 Bl. - Augsburg, Univ. Diss., 199