Photon-Modulated Bond Covalency of [Sm(II)(η9-C9H9)2].

Lanthanides are widely assumed not to form covalent bonds due to the localized nature of their 4f valence electrons. This work demonstrates that the ionic bond of Sm(II) with cyclononatetraenyl (η9-C9H9-) in [Sm(η9-C9H9)2] can be modulated and becomes more covalent by photon-induced transfer of Sm 4f electrons to Sm 5d orbitals. This photon-induced change in bonding properties facilitates a subsequent reconfiguration of [Sm(η9-C9H9)2]. As a result, Sm-C bond length contraction is detected and the local Sm coordination environment exhibits more extensive disorder. Both Sm 4f and 5d electrons have increased participation in covalent Sm-ligand interactions. The Sm L3-edge valence band resonant inelastic X-ray scattering (VB-RIXS), high-resolution X-ray absorption near-edge structure (HR-XANES), and quantum chemical computations showcase a spectroscopic methodology for in-depth studies of bond covalency of lanthanide atoms.

Identification of Clostridium innocuum hypothetical protein that is cross-reactive with C. difficile anti-toxin antibodies.

OBJECTIVES: Previously considered solely an opportunistic pathogen, Clostridium innocuum (CI) was recently reported in Taiwan to be an emerging cause of antibiotic-associated diarrhea and clinically indistinguishable from Clostridioides difficile (CD) infection. We previously identified CI culture supernatant being cross-reactive with commercial CD toxin enzyme immunoassays. We aimed to identify and characterize the cross-reacting protein and determine whether it functioned as a human toxin. METHODS: We performed western blots using CI culture supernatants and CD anti-toxin antibodies and identified interacting bands. We identified protein(s) using tandem mass spectrometry and evaluated them by cytotoxicity assays. RESULTS: CI, but not CD, was isolated from stool of 12 children and adults with diarrhea. Culture supernatant from 6/12 CI isolates, and an ATCC reference strain, tested positive for CD toxins (total 7/13 isolates) by commercial EIA. Using two of these isolates, we identified two ∼40 kDa hypothetical proteins, CI_01447 and CI_01448, and confirmed cross-reactivity with CD anti-toxin antibodies by enzyme immunoassay and Western blot. Whole-genome sequencing confirmed all 13 isolates contained both genes, which were highly conserved. We observed no cytopathic or cytotoxic effects to HeLa cells when treated with these proteins. We identified amino acid sequence similarity to the NlpC/P60 family of proteins. CONCLUSIONS: Our findings do not suggest CI proteins CI_01448 and CI_01447, which cross-react with antibodies against CD toxins A and B, are toxic to HeLa cells. Further studies are needed to determine the function of these cross-reacting proteins and the potential virulence factors that could be responsible for CI diarrheal disease.

[Pager-supported waiting time management in a university hospital ENT outpatient department : A pilot project for more distance and more comfort]. / Pager-gestütztes Wartezeitmanagement in einer universitären HNO-Ambulanz : Pilotprojekt für mehr Abstand und für mehr Komfort.

BACKGROUND: Due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, sufficient distance between people is absolutely necessary, especially in waiting rooms of medical care institutions. This is frequently difficult to realize due to restricted spatial capacities. OBJECTIVE: This study investigated the possibility of enabling patients to spend the waiting period outside of the waiting room of the ENT outpatient department, in order to reduce the number of patients in the waiting rooms and therefore observe distancing rules. This was realized by the use of a pager system. MATERIALS AND METHODS: During the timeframe of 12.5 weeks (04.06.2020-31.08.2020), ENT outpatients were issued with pagers. The patients could thus move freely within the hospital and grounds. The pager system was activated 10-15 min before the appointment, to call patients back to the outpatient ENT clinic. questionnaires were used to evaluate the system and examine patients' acceptance and satisfaction. RESULTS: The 137 questionnaires analyzed showed satisfaction with the system, not only regarding distancing rules but also with the more comfortable waiting time. CONCLUSION: Introduction of a pager system for patients could help to meet hygiene and distance rules, and also increase comfort during (often unavoidable) waiting times for patients in the university hospital ENT outpatient department. The long-term use of such a system seems promising.

Patients with breakthrough tick-borne encephalitis suffer a more severe clinical course and display extensive magnetic resonance imaging changes.

BACKGROUND AND PURPOSE: Tick-borne encephalitis (TBE) is a common viral disease in central Europe and Asia. Severe or even lethal neurological symptoms may ensue. With limited therapeutic options, active vaccination against the TBE virus (TBEV) is strongly recommended in endemic areas. A systematic analysis of the clinical picture and cerebral imaging findings associated with TBE was conducted with particular focus on patients who acquired TBE despite previous vaccination. METHODS: A cohort of 52 patients with serologically proven TBE treated at our centre in a 10-year period who received at least one cerebral magnetic resonance imaging (MRI) was retrospectively described. Extension of MRI changes was systematically assessed by an experienced neuroradiologist. Standard statistical procedures were performed. RESULTS: Fifty-two patients with a definite serological diagnosis of TBE were included. The most common presentation was encephalitis (67%). MRI showed TBE-associated parenchymal lesions in 33% of all patients. Sites of predilection included the periaqueductal grey, the thalamus and the brainstem. Ten patients had received at least one prior active or passive TBEV immunization. All of these had a maximal Rankin Scale score of at least 4. The median number of affected anatomical regions on MRI was significantly higher than in the non-vaccinated cohort. CONCLUSIONS: To our knowledge, this is the first study systematically describing the peculiarities of MRI in patients vaccinated against TBE. In addition to a severe clinical course, they exhibit more extensive MRI lesions than a non-vaccinated cohort. Possible reasons for these findings include incomplete seroconversion, more virulent TBEV strains or antibody-dependent enhancement.

Adenosine stress CMR perfusion imaging of the temporal evolution of perfusion defects in a porcine model of progressive obstructive coronary artery occlusion.

Adenosine stress CMR perfusion imaging can quantify absolute perfusion and myocardial perfusion reserve (MPR) in coronary artery disease (CAD) with higher spatial resolution than positron emission tomography, the only clinically available technique for quantitative myocardial perfusion imaging. While porcine models of CAD are excellent for studying perfusion abnormalities in chronic CAD, to date there are a limited number of studies that use quantitative perfusion for evaluation. Therefore, we developed an adenosine stress CMR protocol to evaluate the temporal evolution of perfusion defects in a porcine model of progressive obstructive CAD. 10 Yucatan minipigs underwent placement of an ameroid occluder around the left circumflex artery (LCX) to induce a progressive chronic coronary obstruction. Four animals underwent a hemodynamic dose range experiment to determine the adenosine dose inducing maximal hyperemia. Each animal had a CMR examination, including stress/rest spiral quantitative perfusion imaging at baseline and 1, 3, and 6 weeks. Late gadolinium enhancement images determined the presence of myocardial infarction, if any existed. Pixelwise quantitative perfusion maps were generated using Fermi deconvolution. The results were statistically analyzed with a repeated mixed measures model to block for physiological variation between the animals. Five animals developed myocardial infarction by 3 weeks, while three developed ischemia without an infarction. The perfusion defects were located in the inferolateral myocardium in the perfusion territory of the LCX. Stress perfusion values were higher in remote segments than both the infarcted and ischemic segments (p < 0.01). MPR values were significantly greater in the remote segments than infarcted and ischemic segments (p < 0.01). While the MPR decreased in all segments, the MPR recovered by the sixth week in the remote regions. We developed a model of progressive CAD and evaluated the temporal evolution of the development of quantitative perfusion defects. This model will serve as a platform for understanding the development of perfusion abnormalities in chronic occlusive CAD.

Patient's perception: shorter and more severe prodromal phase in GBA-associated PD.

BACKGROUND: Prevalence and time of occurrence of prodromal symptoms of Parkinson's disease (PD) in relation to the onset of classical motor manifestation varies between patients. Possible modifying factors might be different genetic architectures predisposing to varying burden of manifestations. OBJECTIVES: To characterize the prodromal phase in PD patients with heterozygous mutations in the GBA gene compared to PD patients without GBA mutation. METHODS: In a retrospective design, 151 participants [47 PD patients carrying a GBA mutation (PDGBA ), 52 idiopathic PD patients (PDidiopathic ), 52 healthy elderly (CON)] underwent a validated structured interview designed to assess prevalence and time of occurrence of prodromal symptoms. RESULTS: PDGBA showed a higher prevalence of prodromal symptoms and almost simultaneous occurrence of non-motor and early motor symptoms shortly before PD diagnosis whereas PDidiopathic reported a longer prodromal phase starting with non-motor symptoms. CONCLUSION: The short and severe prodromal phase in PDGBA might call for shorter assessment intervals in yet premanifest GBA mutation carriers.

The presence of occipital hair in the pilonidal sinus cavity-a triple approach to proof.

PURPOSE: Hair in the pilonidal sinus is not growing within the sinus cavity, as hair follicles are not present there. Not few pilonidal patients do not have intergluteal hair, which is said to be the causative agent of folliculitis and pilonidal genesis. So, what is the real source of the hair forming the typical pilonidal hair nest? METHODS: A trifold approach was used: First, axial hair strength testing of pilonidal hair and body hair harvested from head, lower back (glabella sacralis), and cranial third of intergluteal fold. Hair strength match was compared clinically. Second, comparative morphological examination by expert forensic biologist of hair from sinus and dorsal body hair. Third, statistical Bayesian classification of every single sinus hair based on its strength was done to determine the most probable region of origin. RESULTS: Using clinical hair strength comparison, in 13/20 patients, head hair is the stiffest hair, followed by intergluteal hair. Only in 6/20 patients, this is the case with hair from the glabella sacralis. According to comparative morphological comparison, a minimum of 5 of 13 hair nests with possible hair allocation examined contain hair from the occiput. In 5/18 nests, hair could not be determined to a specific location though. Statistical classification with correction for multiple testing shows that 2 nests have hair samples that are at least 100 times more probable to originate from head or lower back than from intergluteal fold. CONCLUSION: We saw our null hypothesis that "hair in the sinus cavity is from the intergluteal region" rejected by each of three different approaches. There is strong evidence that occipital hair is present regularly in pilonidal sinus nests. We should start thinking of occipital hair as an important hair source for the development of the pilonidal hair nest.

Quantitative STEM Imaging of Order-Disorder Phenomena in Double Perovskite Thin Films.

Using aberration-corrected high-angle annular dark field scanning transmission electron microscopy (HAADF-STEM), we investigate ordering phenomena in epitaxial thin films of the double perovskite Sr_{2}CrReO_{6}. Experimental and simulated imaging and diffraction are used to identify antiphase domains in the films. Image simulation provides insight into the effects of atomic-scale ordering along the beam direction on HAADF-STEM intensity. We show that probe channeling results in ±20% variation in intensity for a given composition, allowing 3D ordering information to be probed using quantitative STEM.

GBA-associated parkinsonism and dementia: beyond α-synucleinopathies?

BACKGROUND AND PURPOSE: To date the role of GBA mutations beyond α-synucleinopathies in the parkinsonism-dementia spectrum is still unclear. The aim of the study was to screen for GBA mutations in progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), primary progressive aphasia (PPA) and the behavioural variant of frontotemporal dementia (bvFTD). METHODS: In all, 303 patients with a clinical diagnosis of PSP (n = 157), CBS (n = 39), PPA (n = 35) and bvFTD (n = 72) and 587 neurologically healthy controls were screened for the most common GBA mutations. RESULTS: GBA mutations were detected in one healthy control and four patients with a clinical diagnosis of PSP (n = 1), probable CBS (n = 2) and PPA (n = 1, with concomitant C9orf72 expansion). Overall the prevalence of GBA mutations was low in non-α-synucleinopathies but significantly higher in the CBS subgroup compared to controls. CONCLUSION: Although numbers are small, our findings indicate that the clinical phenotype of GBA-associated neurodegenerative disease is more heterogeneous than previously assumed, including phenotypes not usually associated with underlying α-synucleinopathies. This may be of relevance, once causal therapeutic strategies for GBA-associated neurodegenerative disease are developed.

[Stromal cells as coordinators of adaptive immune response and immunological memory]. / Stromazellen als Koordinatoren für die adaptive Immunantwort und das immunologische Gedächtnis.

The Greek term stroma literally means in translation mattress, covering or bed. In the medical context this describes the connective tissue framework of an organ which is composed of the stromal cells and the extracellular matrix components which are produced by these cells. According to the original definition stromal cells have a non-hematopoietic origin and adherently grow in cell culture. Nowadays the term is used to cover a heterogeneous group of connective tissue cells of mesenchymal origin which includes fibroblasts, reticular stromal cells and endothelial cells as well as tissue-specific connective tissue cells, such as osteoblasts and adipocytes. Because the stromal cells in the various tissues are very different with respect to morphology and functional characteristics, the manifold aspects of the individual stromal cell populations are now just beginning to be understood. This article presents a summary of new knowledge on the various functions of stromal cells in the immune response.

Regulating Brownian fluctuations with tunable microscopic magnetic traps.

A major challenge to achieving positional control of fluid borne submicron sized objects is regulating their Brownian fluctuations. We present a magnetic-field-based trap that regulates the thermal fluctuations of superparamagnetic beads in suspension. Local domain-wall fields originating from patterned magnetic wires, whose strength and profile are tuned by weak external fields, enable the bead trajectories within the trap to be managed and easily varied between strong confinements and delocalized spatial excursions that are described remarkably well by simulations.

Association between albuminuria, glomerular filtration rate and mortality or recurrence in stroke patients.

BACKGROUND/AIMS: In an attempt to find new predictors of stroke prognosis, we evaluated the association of albuminuria (AUr) and the estimated glomerular filtration rate (eGFR) with the recurrence of stroke and mortality. METHODS: We evaluated and followed for at least 7 months patients with first-ever stroke or transient ischemic attack admitted to a prospective cohort from March 2005 to December 2007. We analyzed traditional CV risk factors, albumin-to-creatinine ratio and eGFR (ml/min/1.73 m(2)) as predictors of mortality or recurrence. RESULTS: From a total of 185 patients included [57% (104/185) men, 64 ± 13 years], 38 patients suffered from a recurrent stroke or died, with a mean follow-up of 25.1 ± 8.7 months. AUr (≥30 mg/g) was found in 50.2% (93/185), and 38.9% (72/185) presented an eGFR <60. In univariate analysis, age >65 years, eGFR ≤50, atrial fibrillation (AF), no alcohol intake and AUr >17 mg/g were associated with the composite endpoint. In a multivariate analysis, AF and AUr >17 mg/g were independent predictors of the composite endpoints, but eGFR ≤50 was not. CONCLUSION: The presence of AUr >17 mg/g is independently associated with death or recurrence after stroke. Further studies should consider the AUr as a predictor for a worse prognosis in these patients.

Manipulation of magnetically labeled and unlabeled cells with mobile magnetic traps.

A platform of discrete microscopic magnetic elements patterned on a surface offers dynamic control over the motion of fluid-borne cells by reprogramming the magnetization within the magnetic bits. T-lymphocyte cells tethered to magnetic microspheres and untethered leukemia cells are remotely manipulated and guided along desired trajectories on a silicon surface by directed forces with average speeds up to 20 microm/s. In addition to navigating cells, the microspheres can be operated from a distance to push biological and inert entities and act as local probes in fluidic environments.

Sevelamer decreases systemic inflammation in parallel to a reduction in endotoxemia.

INTRODUCTION: Uremic toxins play a pivotal role in the development of systemic complications of chronic kidney disease (CKD), which are largely mediated by the activation of the immune system. Triggers of inflammation in CKD are largely unknown and strategies aiming to reduce circulating ligands that could start the inflammatory response are potentially important. In the present study, we investigated the impact of sevelamer hydrochloride treatment in reducing endotoxemia and inflammation in a group of hemodialysis (HD) patients. MATERIAL AND METHODS: HD patients, who were converted from calcium carbonate treatment to sevelamer according to KDOQI guidelines, were included and prospectively followed for 6 months. Systemic inflammation was evaluated by serum ultra-high-sensitivity C-reactive protein (hsCRP) using an automated immunoturbidimetric assay. Endotoxin was measured using Limulus amebocyte lysate chromogenic endpoint assay. All the analyses were performed immediately before conversion and after 6 months of treatment. RESULTS: After the exclusion of patients discontinuing the treatment, 20 patients (mean dialysis time 12 +/- 4 months on HD, age 52 +/- 2 years, 38% males, 11% diabetics) were included in the analysis. No significant changes were observed in Ca, P and PTH levels, while a reduction in cholesterol levels was seen. Plasma concentration of hsCRP and endotoxin significantly decreased after 6 months of conversion to sevelamer compared with baseline. CONCLUSION: We conclude that sevelamer treatment leads to a decrease in hsCRP levels, which was accompanied by a parallel decrease in endotoxemia, suggesting that endotoxemia may contribute to the systemic inflammation in HD patients, which was partially reduced by the use of sevelamer.

Interhemispheric correlation of late pleistocene glacial events.

A radiocarbon chronology shows that piedmont glacier lobes in the Chilean Andes achieved maxima during the last glaciation at 13,900 to 14,890, 21,000, 23,060, 26,940, 29,600, and >/=33,500 carbon-14 years before present ((14)C yr B.P.) in a cold and wet Subantarctic Parkland environment. The last glaciation ended with massive collapse of ice lobes close to 14,000(14)C yr B.P., accompanied by an influx of North Patagonian Rain Forest species. In the Southern Alps of New Zealand, additional glacial maxima are registered at 17,720(14)C yr B.P., and at the beginning of the Younger Dryas at 11,050 (14)C yr B. P. These glacial maxima in mid-latitude mountains rimming the South Pacific were coeval with ice-rafting pulses in the North Atlantic Ocean. Furthermore, the last termination began suddenly and simultaneously in both polar hemispheres before the resumption of the modern mode of deep-water production in the Nordic Seas. Such interhemispheric coupling implies a global atmospheric signal rather than regional climatic changes caused by North Atlantic thermohaline switches or Laurentide ice surges.

Antibody to aquaporin-4 in the long-term course of neuromyelitis optica.

Neuromyelitis optica (NMO) is a severe inflammatory CNS disorder of putative autoimmune aetiology, which predominantly affects the spinal cord and optic nerves. Recently, a highly specific serum reactivity to CNS microvessels, subpia and Virchow-Robin spaces was described in patients with NMO [called NMO-IgG (NMO-immunoglobulin G)]. Subsequently, aquaporin-4 (AQP4), the most abundant water channel in the CNS, was identified as its target antigen. Strong support for a pathogenic role of the antibody would come from studies demonstrating a correlation between AQP4-Ab (AQP4-antibody) titres and the clinical course of disease. In this study, we determined AQP4-Ab serum levels in 96 samples from eight NMO-IgG positive patients (median follow-up 62 months) in a newly developed fluorescence-based immunoprecipitation assay employing recombinant human AQP4. We found that AQP4-Ab serum levels correlate with clinical disease activity, with relapses being preceded by an up to 3-fold increase in AQP4-Ab titres, which was not paralleled by a rise in other serum autoantibodies in one patient. Moreover, AQP4-Ab titres were found to correlate with CD19 cell counts during therapy with rituximab. Treatment with immunosuppressants such as rituximab, azathioprine and cyclophosphamide resulted in a marked reduction in antibody levels and relapse rates. Our results demonstrate a strong relationship between AQP4-Abs and clinical state, and support the hypothesis that these antibodies are involved in the pathogenesis of NMO.

Comparison of the lattice-Boltzmann model with the finite-difference time-domain method for electrodynamics.

A three-dimensional lattice-Boltzmann model (LBM) for the simulation of the Maxwell equations is presented. The inclusion of media follows an extension of a special limit described in the literature which is applicable to this LBM and does not harm the stability of simulations. The focus of the present study lies on the properties of numerical accuracy and stability of the LBM in comparison to the standard finite-difference time-domain (FDTD) method based on Yee's method. Typical examples, often investigated in the context of numerical simulations, are considered. These include the propagation of electrodynamic (EM) fields in one- and three-dimensional systems. Results of this simulations are compared to the ones of their theoretical predictions. Further on, long-time simulations are done in systems with periodic boundary conditions to check if the total energy is conserved. To investigate the effect of the numeric impedance, the propagation of an EM pulse is monitored spatially and temporarily in a two-dimensional system. The simulation results indicate, in contrast to the one obtained from the FDTD method, that the presented LBM does fulfill the expected energy conservation and is not effected by the numerical impedance. This LBM therefore represents a valuable alternative for the simulation of EM problems like long-time simulations by avoiding intrinsic properties the FDTD method suffers from.

ASC acts in a caspase-1-independent manner to worsen acute pneumonia caused by Pseudomonas aeruginosa.

PURPOSE: Pseudomonas aeruginosa expresses a type III secretion system (T3SS) that activates the host inflammasome-mediated immune response. We examined the role of inflammasome activation in severe infection outcomes. METHODS: We infected C57BL/6 (B6) mice lacking inflammasome components ASC or caspase-1/11 with a highly virulent strain of P. aeruginosa, PSE9, using a mouse model of pneumonia. We evaluated inflammasome activation in vitro by infecting bone marrow-derived macrophages (BMDMs) with PSE9 and measuring cell death and release of inflammasome-dependent cytokines IL-18 and IL-1ß. A bioluminescent reporter assay was used to detect activity of caspase-1 and caspase-3/7 in BMDMs from B6 and ASC-deficient mice.Results/Key Findings. ASC-/- mice exhibited significantly improved survival relative to caspase-1/11-/- mice and B6 mice, demonstrating that ASC and caspase-1/11 play differential roles in P. aeruginosa infection. We found that ASC-/- BMDMs exhibited significantly reduced cell death relative to B6 BMDMs, while caspase-1/11-/- BMDMs were resistant to cell death. IL-18 and IL-1ß were both detected from supernatants of infected B6 BMDMs, but cytokine release was abrogated in both ASC-/- and caspase-1/11-/- BMDMs. We detected a 2.5-fold increase in the activation of caspase-3/7 in PSE9-infected B6 BMDMs, but no increase in infected ASC-/- BMDMs. Cell death, cytokine release and caspase-3/7 activity were dependent on a functional T3SS. CONCLUSIONS: Collectively, these results are consistent with a model whereby the T3SS apparatus of P. aeruginosa activates the caspase-1-dependent inflammasome and caspase-3/7 through an ASC-dependent mechanism. This activation may have implications for the outcomes of P. aeruginosa infections.