Crucial role of local peroxynitrite formation in neutrophil-induced endothelial cell activation

Introduction and methods: The reaction of superoxide anions and NO not only results in a decreased availability of NO, but also leads to the formation of peroxynitrite, the role of which in the cardiovascular system is still discussed controversially. In cultured human endothelial cells, we studied whether there is a significant interaction between endothelial NO and neutrophil-derived superoxide anions in terms of endothelial peroxynitrite formation. We particularly studied whether a significantly higher redox-stress can be found in those endothelial cells directly adjacent to an activated neutrophil. Results: A considerable part of the 2,7-dihydrodichlorofluoresceine signal in endothelial cells was due to oxidation by peroxynitrite. Providing superoxide radicals by enzymatic source or by the neutrophil respiratory burst increased the fluorescence, which was attenuated by blockade of endothelial NO-synthase, suggesting that peroxynitrite was formed from neutrophil- or extracellular enzyme-derived superoxide and endothelial NO. Considerably higher fluorescence intensity was observed in endothelial cells in direct neighborhood to a neutrophil. This was particularly pronounced in the presence of a NO-donor and was accompanied by a strong activation of NF-κB and increased expression of E-selectin in these cells. Conclusion: Endothelial cells adjacent to neutrophils may have elevated levels of peroxynitrite that result in an increased expression of adhesion molecules. Such cells might represent a preferential site for adhesion and migration of additional neutrophils when simultaneously high concentrations of NO and neutrophil-derived superoxide are present

Seroprevalence of SARS-CoV-2 in healthcare workers from outpatient facilities and retirement or nursing homes in a Swiss canton.

BACKGROUND Healthcare workers are more frequently exposed to SARS-CoV-2 than the general population. Little is known about healthcare settings outside of hospitals. We studied the seroprevalence of SARS-CoV-2 among healthcare workers in outpatient facilities and retirement or nursing homes in the Canton of Solothurn, Switzerland in the first wave of the COVID-19 pandemic. METHODS Longitudinal seroprevalence study among healthcare workers with examinations at baseline and 2 months between June and September 2020. The Abbott SARS-CoV-2 IgG and Liaison/Diasorin SARS-CoV-2 S1/S2 IgG assay were used to detect antibodies against SARS-CoV-2. All participants provided demographic information. We report descriptive statistics and calculated the seroprevalence with 95% confidence intervals. RESULTS We included 357 healthcare workers; their median age was 43 years (interquartile range 29-54), and 315 (88.2%) were female. Forty-nine (13.7%) were physicians, 87 (24.4%) practice assistants and 221 (61.9%) nurses. Overall seroprevalence among healthcare workers in outpatient facilities and retirement or nursing homes was 3.4% (12/357). The 12 seropositive healthcare workers were all nurses (12/221, 5.5%); 11 worked at retirement or nursing homes and one at the hospital's outpatient clinic. Symptoms such as loss of smell or taste, shortness of breath, and fever were more prevalent among seropositive healthcare workers than seronegative healthcare workers. No close contact had detectable antibodies against SARS-CoV-2. CONCLUSIONS Seroprevalence among healthcare workers was low, but higher among nursing staff of retirement or nursing homes. Healthcare workers at private practices were able to protect themselves well during the first wave of the COVID-19 pandemic

PEDIATRIC TULAREMIA– A CASE SERIES FROM A SINGLE CENTER IN SWITZERLAND

Background The incidence of tularemia has recently increased throughout Europe. Pediatric tularemia typically presents with ulceroglandular or glandular disease and requires antimicrobial therapy not used in the empirical management of childhood acute lymphadenitis. We describe the clinical presentation and course in a case series comprising 20 patients. Methods Retrospective analysis of a single-center case series of microbiologically confirmed tularemia in patients below 16 years of age diagnosed between 2010 and 2021. Results Nineteen patients (95%) presented with ulceroglandular (n = 14) or glandular disease (n = 5), respectively. A characteristic entry site lesion (eschar) was present in 14 (74%). Fever was present at illness onset in 15 patients (75%) and disappeared in all patients before targeted therapy was initiated. The diagnosis was confirmed by serology in 18 patients (90%). While immunochromatography (ICT) was positive as early as on day 7, a microagglutination test (MAT) titer 1:≥160 was found no earlier than on day 13. Sixteen patients (80%) were initially treated with an antimicrobial agent ineffective against F. tularensis. The median delay (range) from illness onset to initiation of targeted therapy was 12 days (range, 6-40). Surgical incision and drainage was ultimately performed in 12 patients (60%). Conclusion Pediatric tularemia in Switzerland usually presents with early, self-limiting fever, and a characteristic entry site lesion with regional lymphadenopathy draining the scalp or legs. Particularly in association with a tick exposure history, this presentation may allow early first-line therapy with an agent specifically targeting F. tularensis, potentially obviating the need for surgical therapy

Virtual single-photon transition interrupted: time-gated optical gain and loss

The response of matter to an optical excitation consists essentially of absorption and emission. Traditional spectroscopy accesses the frequency-resolved and time-integrated response, while the temporal evolution stays concealed. However, we will demonstrate here that the temporal evolution of a virtual single-photon transition can be mapped out by a second pulsed electromagnetic field. The resulting optical signal shows previously unexpected optical gain and loss, which can be gated and controlled via the relative delay of the electromagnetic fields. The model presented here can be applied to any system that assumes a two-level character through near-resonant optical dipole excitation, whether they are of atomic, molecular or even solid-state nature. These theoretical observations are in excellent qualitative agreement with our transient absorption spectroscopy study in helium. The presented results can act as starting point for a new scheme for creating optical gain, which is a prerequisite for the operation of lasers. It may be possible to open the doors to spectral regions, which were difficult to access until now, e.g. in the extreme ultraviolet.Comment: 15 pages, 4 figure

Symmetries of perturbed conformal field theories

The symmetries of perturbed conformal field theories are analysed. We explain which generators of the chiral algebras of a bulk theory survive a perturbation by an exactly marginal bulk field. We also study the behaviour of D-branes under current-current bulk deformations. We find that the branes always continue to preserve as much symmetry as they possibly can, i.e. as much as is preserved in the bulk. We illustrate these findings with several examples, including permutation branes in WZW models and B-type D-branes in Gepner models.Comment: 30 pages, 3 figures. V2: Small error in eq. (2.14) correcte

Detection of pneumonia associated pathogens using a prototype multiplexed pneumonia test in hospitalized patients with severe pneumonia

Severe pneumonia remains an important cause of morbidity and mortality. Polymerase chain reaction (PCR) has been shown to be more sensitive than current standard microbiological methods--particularly in patients with prior antibiotic treatment--and therefore, may improve the accuracy of microbiological diagnosis for hospitalized patients with pneumonia. Conventional detection techniques and multiplex PCR for 14 typical bacterial pneumonia-associated pathogens were performed on respiratory samples collected from adult hospitalized patients enrolled in a prospective multi-center study. Patients were enrolled from March until September 2012. A total of 739 fresh, native samples were eligible for analysis, of which 75 were sputa, 421 aspirates, and 234 bronchial lavages. 276 pathogens were detected by microbiology for which a valid PCR result was generated (positive or negative detection result by Curetis prototype system). Among these, 120 were identified by the prototype assay, 50 pathogens were not detected. Overall performance of the prototype for pathogen identification was 70.6% sensitivity (95% confidence interval (CI) lower bound: 63.3%, upper bound: 76.9%) and 95.2% specificity (95% CI lower bound: 94.6%, upper bound: 95.7%). Based on the study results, device cut-off settings were adjusted for future series production. The overall performance with the settings of the CE series production devices was 78.7% sensitivity (95% CI lower bound: 72.1%) and 96.6% specificity (95% CI lower bound: 96.1%). Time to result was 5.2 hours (median) for the prototype test and 43.5 h for standard-of-care. The Pneumonia Application provides a rapid and moderately sensitive assay for the detection of pneumonia-causing pathogens with minimal hands-on time

Die maximal tragbare Radlast – eine zweckmässige Kenngrösse für die Praxis

Hohe Radlasten führen vor allem in Unterböden zu Druckbelastungen, die dauerhafte Verformungen und damit Beeinträchtigungen der Bodenfunktionen und der Ertragsfähigkeit verursachen. Die maximal tragbare Radlast ist jene Radlast, bei der die Bodenbelastung gerade noch unterhalb der Bodenfestigkeit (bestimmt als Vorbelastung) liegt und die Bodenstruktur deshalb noch nicht dauerhaft verformt wird. Wir berechneten die saisonalen Veränderungen der maximal tragbaren Radlast für die beiden Anbausysteme Direktsaat und Pflug sowie für den Dauergrünlandstreifen zwischen den Versuchsparzellen der Dauerbeobachtungsfläche Oberacker (sandiger Lehm). Gemessen wurde die Bodenfeuchtigkeit (als Matrixpotenzial) in situ und die Vorbelastung bei verschiedenen Matrixpotenzialen an ungestörten Zylinderproben im Labor. Die Simulationen wurden für eine Referenztiefe von 35 cm sowohl für Standardreifen als auch für Niederdruckreifen durchgeführt. Es zeigte sich, dass sowohl die Vorbelastung als auch die maximal tragbare Radlast stark von der Bodenfeuchtigkeit abhängig sind. Bei Niederdruckreifen ist die maximal tragbare Radlast höher als bei Standardreifen. Die Anzahl Tage, an denen der Boden ohne Verdichtungsrisiko befahren werden kann, schwankt stark von Jahr zu Jahr, ist beim Pflugsystem leicht höher als beim Direktsaatsystem und nimmt mit steigender Radlast ab. Die Darstellung des Verdichtungsrisikos mit dem Parameter «maximal tragbare Radlast» ist einfach zu interpretieren und deshalb nützlich für die Prävention von Bodenverdichtungen

Turing instabilities in a mathematical model for signaling networks

GTPase molecules are important regulators in cells that continuously run through an activation/deactivation and membrane-attachment/membrane-detachment cycle. Activated GTPase is able to localize in parts of the membranes and to induce cell polarity. As feedback loops contribute to the GTPase cycle and as the coupling between membrane-bound and cytoplasmic processes introduces different diffusion coefficients a Turing mechanism is a natural candidate for this symmetry breaking. We formulate a mathematical model that couples a reaction-diffusion system in the inner volume to a reaction-diffusion system on the membrane via a flux condition and an attachment/detachment law at the membrane. We present a reduction to a simpler non-local reaction-diffusion model and perform a stability analysis and numerical simulations for this reduction. Our model in principle does support Turing instabilities but only if the lateral diffusion of inactivated GTPase is much faster than the diffusion of activated GTPase.Comment: 23 pages, 5 figures; The final publication is available at http://www.springerlink.com http://dx.doi.org/10.1007/s00285-011-0495-