Increased risk of acute stroke among patients with severe COVID-19: a multicenter study and meta-analysis.

BACKGROUND AND PURPOSE: Recent observations linked coronavirus disease 2019 (COVID-19) to thromboembolic complications possibly mediated by increased blood coagulability and inflammatory endothelial impairment. We aimed to define the risk of acute stroke in patients with severe and non-severe COVID-19. METHODS: We performed an observational, multicenter cohort study in four participating hospitals in Saxony, Germany to characterize consecutive patients with laboratory-confirmed COVID-19 who experienced acute stroke during hospitalization. Furthermore, we conducted a systematic review using PubMed/MEDLINE, Embase, Cochrane Library and bibliographies of identified papers following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines including data from observational studies of acute stroke in COVID-19 patients. Data were extracted by two independent reviewers and pooled with multicenter data to calculate risk ratios (RRs) and 95% confidence intervals (95% CIs) for acute stroke related to COVID-19 severity using a random-effects model. Between-study heterogeneity was assessed using Cochran's Q and I2 statistics. International Prospective Register of Systematic Reviews registration number: CRD42020187194. RESULTS: Of 165 patients hospitalized for COVID-19 (49.1% males, median age = 67 years [57-79 years], 72.1% severe or critical) included in the multicenter study, overall stroke rate was 4.2% (95% CI: 1.9-8.7). Systematic literature search identified two observational studies involving 576 patients that were eligible for meta-analysis. Amongst 741 pooled COVID-19 patients, overall stroke rate was 2.9% (95% CI: 1.9-4.5). Risk of acute stroke was increased for patients with severe compared to non-severe COVID-19 (RR = 4.18, 95% CI: 1.7-10.25; P = 0.002) with no evidence of heterogeneity (I2  = 0%, P = 0.82). CONCLUSIONS: Synthesized analysis of data from our multicenter study and previously published cohorts indicates that severity of COVID-19 is associated with an increased risk of acute stroke.

Influence of texture and grain misorientation on the ionic conduction in multilayered solid electrolytes - interface strain effects in competition with blocking grain boundaries.

Interface strain and its influence on the ionic transport along hetero-interfaces has gained a lot of attention over the last decade and is controversially discussed. We investigate the relaxation of mismatch induced interfacial strain as a function of the degree of orientation/texture of the columnar crystallites and assess the impact on the oxygen ion conductivity in Er2O3/YSZ multilayer systems. Results from X-ray diffraction clearly show, that the width of the strained hetero-interface region increases with an increasing degree of orientation of the crystallites. The combined impact of film texture and strain at the hetero-interfaces of the film on the ionic conductivity however is not easily deduced from these measurements. The samples with the highest degree of orientation, i.e. with only one azimuthal variant, show strong anisotropic electrical properties. In samples with a lower degree of orientation, i.e. samples with a fiber texture, anisotropic properties cannot be detected, possibly due to a geometrical averaging of the electrical properties. The expected strain induced monotonic increase of the ionic conductivity with decreasing layer thickness and thus increasing interfacial influence could only be detected for samples with a fiber texture and a considerable degree of crystallite misorientation. This leads to the important conclusion that the texture and therefore the nature of the grain boundaries and their network influence the ionic conductivity of the multilayer thin films in the same order of magnitude as the misfit induced interface strain. Thus, the potential design of strain-controlled ionic conductors requires additionally the control of the microstructure in terms of grain orientation.

Ballistic Transport and Exchange Interaction in InAs Nanowire Quantum Point Contacts.

One-dimensional ballistic transport is demonstrated for a high-mobility InAs nanowire device. Unlike conventional quantum point contacts (QPCs) created in a two-dimensional electron gas, the nanowire QPCs represent one-dimensional constrictions formed inside a quasi-one-dimensional conductor. For each QPC, the local subband occupation can be controlled individually between zero and up to six degenerate modes. At large out-of-plane magnetic fields Landau quantization and Zeeman splitting emerge and comprehensive voltage bias spectroscopy is performed. Confinement-induced quenching of the orbital motion gives rise to significantly modified subband-dependent Landé g factors. A pronounced g factor enhancement related to Coulomb exchange interaction is reported. Many-body effects of that kind also manifest in the observation of the 0.7·2e(2)/h conductance anomaly, commonly found in planar devices.

Adiabatic Edge Channel Transport in a Nanowire Quantum Point Contact Register.

We report on a prototype device geometry where a number of quantum point contacts are connected in series in a single quasi-ballistic InAs nanowire. At finite magnetic field the backscattering length is increased up to the micron-scale and the quantum point contacts are connected adiabatically. Hence, several input gates can control the outcome of a ballistic logic operation. The absence of backscattering is explained in terms of selective population of spatially separated edge channels. Evidence is provided by regular Aharonov-Bohm-type conductance oscillations in transverse magnetic fields, in agreement with magnetoconductance calculations. The observation of the Shubnikov-de Haas effect at large magnetic fields corroborates the existence of spatially separated edge channels and provides a new means for nanowire characterization.

Bacterial colonization of microbial biofilms in oral squamous cell carcinoma.

OBJECTIVES: The purpose of this prospective clinical study was to identify the bacterial spectra on the surface of oral squamous cell carcinomas (OSCC) in comparison to oral mucosa of patients with a higher risk to emerge an OSCC and a control group to determine their susceptibility to various common antibiotics. MATERIAL AND METHODS: Swabs from 90 patients, 30 patients of each group, were cultured on media for aerobes and anaerobes and tested with agar diffusion and Etest. RESULTS: The predominant pathogens of the normal healthy oral mucosa were aerobes. The ratio between aerobes and anaerobes was 2:1, balanced in risk patients and inverted in the OSCC group. Altogether, 1,006 isolates were cultured. The most frequent strains were 47 viridans streptococci, 30 Staphylococcus species, 14 Enterococcus faecalis, 36 Neisseria species, 14 Escherichia coli, and 23 other aerobes, 66 Peptostreptococcus species, 39 Fusobacterium species, and 34 Prevotella species. The resistance rates in the OSCC group were penicillin 40%, ampicillin 57%, doxycycline 23%, clindamycin 47%, and amoxicillin/clavulanic acid 20%, but up to 100% of pathogens were susceptible to azithromycin, telithromycin, levofloxacin, and moxifloxacin. CONCLUSION: Gram-negative anaerobes play a decisive role in the development of postoperative infections in patients with OSCC. This tumor special type of colonization does not agree with the normal flora of the oral cavity. CLINICAL RELEVANCE: Biofilms on OSCC surfaces provide an important reservoir for anaerobic bacteria. As a consequence, a proposal for an antibiotic prophylactic regime should be given.

Photoemission spectroscopy study of the lanthanum lutetium oxide/silicon interface.

Rare earth oxides are promising candidates for future integration into nano-electronics. A key property of these oxides is their ability to form silicates in order to replace the interfacial layer in Si-based complementary metal-oxide field effect transistors. In this work a detailed study of lanthanum lutetium oxide based gate stacks is presented. Special attention is given to the silicate formation at temperatures typical for CMOS processing. The experimental analysis is based on hard x-ray photoemission spectroscopy complemented by standard laboratory experiments as Rutherford backscattering spectrometry and high-resolution transmission electron microscopy. Homogenously distributed La silicate and Lu silicate at the Si interface are proven to form already during gate oxide deposition. During the thermal treatment Si atoms diffuse through the oxide layer towards the TiN metal gate. This mechanism is identified to be promoted via Lu-O bonds, whereby the diffusion of La was found to be less important.

[Local flaps for the closure of facial defects]. / Defektdeckung mittels Nahlappenplastiken im Gesicht.

Local flaps for the closure of facial defects after trauma, tumor resection or due to malformations have been well known since ancient times and allow good to satisfying functional and aesthetic results. Based on the characteristics of skin and soft tissue nearly all clinical situations can be resolved by stretching, rotating and transposing flaps depending on the localization. A good surgical technique is essential for the success. The basic principles are briefly described and suggestions for the application of flaps to different localizations are given. For analgesia local anesthesia is sufficient. As could be demonstrated multitudinously the method is ideal for closure of small to large defects in the face; therefore, microvascular surgery can be extremely restricted in treating defects of the face.

Prognostic impact of meningeal dissemination in primary CNS lymphoma (PCNSL): experience from the G-PCNSL-SG1 trial.

BACKGROUND: We evaluated the frequency and prognostic impact of meningeal dissemination (MD) in immunocompetent adult patients with primary central nervous system lymphoma treated in a randomized phase III trial. PATIENTS AND METHODS: MD was evaluated at study entry and defined by lymphoma proof in the meningeal compartment detected by at least one of the following methods: cerebrospinal fluid (CSF) cytomorphology, detection of clonal B cells by IgH PCR in CSF or contrast enhancement of the leptomeninges on magnetic resonance imaging (MRI). RESULTS: Data on MD were available in 415 patients, of those, MD was detected in 65 (15.7%): in 44/361 (12.2%) by CSF cytomorphology, in 16/152 (10.5%) by PCR and in 17/415 (4.1%) by MRI. Major patients' characteristics and therapy did not significantly differ between patients with MD (MD+) versus those without MD (MD-). There was a significant correlation of MD with CSF pleocytosis (>5/µl; P < 0.0001), but no correlation with CSF protein elevation (>45 mg/dl). Median progression-free survival was 6.7 months [95% confidence interval (CI) 0-14.5] in MD+ and 8.3 months (5.7-10.8) in MD- patients (P = 0.95); median overall survival was 21.5 months (95% CI 16.8-26.1) and 24.9 months (17.5-32.3), respectively (P = 0.98). CONCLUSION: MD was detected infrequently and had no impact on outcome in this trial.

Breath chemical markers of sexual arousal in humans.

The chemical composition of exhaled breath was examined for volatile organic compound (VOC) indicators of sexual arousal in human beings. Participants (12-male, 12-female) were shown a randomized series of three emotion-inducing 10-min film clips interspersed with 3-min neutral film clips. The films caused different arousals: sports film (positive-nonsexual); horror film (negative-nonsexual); and erotic (sexual) that were monitored with physiological measurements including genital response and temperature. Simultaneously the breath was monitored for VOC and CO2. While some breath compounds (methanol and acetone) changed uniformly irrespective of the film order, several compounds did show significant arousal associated changes. For both genders CO2 and isoprene decreased in the sex clip. Some male individuals showed particularly strong increases of indole, phenol and cresol coincident with sexual arousal that decreased rapidly afterwards. These VOCs are degradation products of tyrosine and tryptophan, precursors for dopamine, noradrenalin, and serotonin, and therefore represent potential breath markers of sexual arousal.

Randomized comparison of pegfilgrastim day 4 versus day 2 for the prevention of chemotherapy-induced leukocytopenia.

BACKGROUND: To study the effects of deferring pegfilgrastim until day 4 on the reduction of chemotherapy-induced leukocytopenia. PATIENTS AND METHODS: Patients of age 61-80 years with aggressive lymphoma were randomly assigned to receive 6 mg pegfilgrastim on day 2 or 4 of a 2-week chemotherapy regimen (R-CHOP-14). RESULTS: Two hundred and ninety-two and 313 chemotherapy cycles were evaluable in 103 patients. Post-nadir pegfilgrastim serum levels were higher after day 4 than after day 2 application. This was associated with an attenuated leukocyte nadir after day 4 pegfilgrastim and there were fewer days with leukocytes <2 × 10(3)/mm(3) compared with day 2 pegfilgrastim. Grade 3 and 4 leukocytopenias (70% versus 43.3%; P < 0.001) and grade 4-only leukocytopenias (47% versus 20.5%; P < 0.001) were more frequent after day 2 pegfilgrastim. There were more chemotherapy cycles with grade 3 and 4 infections after day 2 than day 4 pegfilgrastim (9.4% versus 6.0%; P = 0.118). Interventional antibiotics were given more often after day 2 than after day 4 pegfilgrastim (30.7% versus 21.9% of cycles; P = 0.008). There were five deaths during leukocytopenia after day 2 and none after day 4 pegfilgrastim (P = 0.027). CONCLUSIONS: Administration of pegfilgrastim on day 4 was more effective in reducing severe leukocytopenias and resulted in fewer deaths during leukocytopenia. Pegfilgrastim should be given on day 4 to better exploit its myeloprotective potential.

Retrospective web-based multicenter evaluation of ¹8F-FDG-PET and CT derived predictive factors. Radioimmunotherapy with yttrium-90-ibritumomab tiuxetan in follicular non Hodgkin's lymphoma.

AIM: Although predictive factors (PF) for conventional lymphoma therapy are established and frequently used in clinical practice and medical research, the PF for radioimmunotherapy (RIT) have not been fully defined until now. The aim of this multicenter evaluation is to prove the feasibility of the multicenter web-based data collection and to preliminary explore imaging findings and prediction of therapy response in patients with follicular lymphoma (FL) following radioimmunotherapy (RIT) with 90Y-ibritumomab tiuxetan. PATIENTS, METHODS: We retrospectively analyzed and correlated clinical and imaging data (CT and FDG-PET) before and after RIT as documented by the RIT-Network. Evaluation of treatment response was done on both patient and lesion basis. Every measurable lesion was analyzed in terms of standardized uptake value (SUV), volume (CT and PET) and response. PF were identified using a uni- and multivariate model. A web-based system was used for the documentation and evaluation of clinical and imaging data. RESULTS: 16 patients with at least one PET before and after RIT were eligible for analysis. Concerning response three months postRIT, 5 patients achieved a CR, 6 patients a PR and 4 patients remained with NC. A total of 159 lesions were measured (mean 10±8). In the multivariate model the log lesion volume (p < 0.0001), the total (p = 0.03) and maximum lesion volume (p = 0.05) were predictors for response (CR + PR). Concerning the lesional CR initial small lesion volume (p = 0.009) and its high metabolic activity (p = 0.01) were identified as predictors. The web-based system showed no major disturbances allowing secure data transfer and central image interpretation in a reasonable time. CONCLUSION: The use of a web-based multicenter archiving system for clinical and imaging data is technically feasible in a multicenter setting and allows a central analysis. This preliminary analysis suggests that FDG-PET may predict the likelihood of response to RIT.

Engineering new limits to magnetostriction through metastability in iron-gallium alloys.

Magnetostrictive materials transduce magnetic and mechanical energies and when combined with piezoelectric elements, evoke magnetoelectric transduction for high-sensitivity magnetic field sensors and energy-efficient beyond-CMOS technologies. The dearth of ductile, rare-earth-free materials with high magnetostrictive coefficients motivates the discovery of superior materials. Fe1-xGax alloys are amongst the highest performing rare-earth-free magnetostrictive materials; however, magnetostriction becomes sharply suppressed beyond x = 19% due to the formation of a parasitic ordered intermetallic phase. Here, we harness epitaxy to extend the stability of the BCC Fe1-xGax alloy to gallium compositions as high as x = 30% and in so doing dramatically boost the magnetostriction by as much as 10x relative to the bulk and 2x larger than canonical rare-earth based magnetostrictors. A Fe1-xGax - [Pb(Mg1/3Nb2/3)O3]0.7-[PbTiO3]0.3 (PMN-PT) composite magnetoelectric shows robust 90° electrical switching of magnetic anisotropy and a converse magnetoelectric coefficient of 2.0 × 10-5 s m-1. When optimally scaled, this high coefficient implies stable switching at ~80 aJ per bit.

Is there an intrinsic limit to the charge-carrier-induced increase of the Curie temperature of EuO?

Rare earth doping is the key strategy to increase the Curie temperature (T(C)) of the ferromagnetic semiconductor EuO. The interplay between doping and charge carrier density (n), and the limit of the T(C) increase, however, are yet to be understood. We report measurements of n and T(C) of Gd-doped EuO over a wide range of doping levels. The results show a direct correlation between n and T(C), with both exhibiting a maximum at high doping. On average, less than 35% of the dopants act as donors, raising the question about the limit to increasing T(C).

Co-expression of Hif1alpha and CAIX is associated with poor prognosis in oral squamous cell carcinoma patients.

BACKGROUND: This study investigates the prognostic impact of the expression of hypoxia-inducible factor 1alpha (Hif1alpha) and carbonic anhydrase IX (CAIX) detected by immunohistochemistry in oral squamous cell carcinoma (OSCC). METHODS: Statistical analysis of immunohistochemical results with clinical parameters including survival outcomes was performed for 80 OSCC patients. RESULTS: Patients with a low expression of both proteins survived on average 54.8 months, whereas those with an increased expression of Hif1alpha in their tumors combined with a low expression of CAIX survived on average only 37.6 months (P = 0.026). In multivariate Cox's regression hazard analysis, again patients with a low expression of Hif1alpha/CAIX had the best prognosis, whereas patients with increased Hif1alpha and low CAIX expression carried a 4.97-fold increased risk of tumor-related death (P = 0.042). CONCLUSION: A co-detection of low Hif1alpha/CAIX expression is significantly correlated with a better prognosis for OSCC patients, which may have implications for therapy options for these patients.

Use of simulation patients in the third section of the medical examination.

In order to protect patients and students during the Covid 19 pandemic, the third section of the medical examination (M3) in Halle (Saale) was conducted in a modified form in accordance with the "Verordnung zur Abweichung von der Approbationsordnung für Ärzte bei einer epidemischen Lage von nationaler Tragweite" [1]. The one-day examination took place at the Dorothea Erxleben Learning Center (DELH) of the Martin Luther University Halle-Wittenberg on standardized simulation subjects. In contrast to previous years, all examiners were examined individually in internal medicine, surgery and their elective subject of the practical year. In the evaluations carried out, the standardized cases were assessed as consistent and fair by examiners and exam takers. Approximately 90% of the examiners could imagine to test a state examination with simulated patients again. After successful pilot testing, a study will be conducted in the coming exam to determine whether the substitution of real patients with simulated patients in the M3 exam can contribute to better standardization and objectivity while maintaining the same high level of acceptance in the exam. Whether the high acceptance will remain constant can only be checked in the course of the study.

Sleep duration and timing in obsessive-compulsive disorder (OCD): evidence for circadian phase delay.

OBJECTIVES: To investigate potential delays in endogenous melatonin in individuals with obsessive-compulsive disorder (OCD). METHODS: First, data are presented for 15 individuals with OCD and matched healthy controls. Next, nine additional participants with OCD who did not have matched controls were added, resulting in a sample of 24 individuals with OCD. All participants were assessed for sleep and circadian rhythm disturbance. Dim light melatonin onset (DLMO) was derived from salivary melatonin and was used in conjunction with sleep diaries, interview measures, and questionnaires. A subset of the OCD group (n = 16) also used actigraphy. RESULTS: In sum, 42% percent (10/24) of the patients with OCD met the criteria for delayed sleep-wake phase disorder (DSWPD) in comparison to 0% in the control sample. DLMO was significantly later in individuals with OCD compared to controls. DLMO and bedtime were not significantly associated with the severity of obsessive-compulsive symptoms or negative affect. CONCLUSIONS: Replication of the findings presented herein, particularly the DLMO results, is warranted. Further, there are now three studies showing that nearly ½ of individuals with OCD meet criteria for a DSWPD. Future studies can explore the mechanisms underlying these connections and the implications of this comorbidity. These findings may increase our understanding of OCD and inform future interventions.

Impact of growth kinetics on the interface morphology and magnetization in La1/3Sr2/3FeO3/La2/3Sr1/3MnO3 heterostructures.

The ability to create atomically perfect, epitaxial heterostructures of correlated complex perovskite oxides using state-of-art thin film deposition techniques has generated new physical phenomena at engineered interfaces. Here we report on the impact of growth kinetics on the magnetic structure and exchange coupling at the interface in heterostructures combining layers of antiferromagnetic La1/3Sr2/3FeO3 (LSFO) and ferromagnetic La2/3Sr1/3MnO3 (LSMO) on (0 0 1)-oriented SrTiO3 (STO) substrates. Two growth orders are investigated, (a) LSMO/LSFO/STO(0 0 1) and (b) LSFO/LSMO/STO(0 0 1), where the LSFO layer is grown by molecular beam epitaxy and the LSMO layer by high oxygen pressure sputtering. The interface has been investigated using electron microscopy and polarized neutron reflectometry. Interdiffusion over seven monolayers is observed in LSMO/LSFO (a) with an almost 50% reduction in magnetization at the interface and showing no exchange coupling. However, the exchange bias effect ([Formula: see text] mT at 10 K) could be realized when the interface is atomically sharp, as in LSFO/LSMO (b). Our study therefore reveals that, even for well ordered and lattice-matched structures, the kinetics involved in the growth processes drastically influences the interface quality with a strong correlation to the magnetic properties.

Radiation of hemocyanin: inactivation and reactivation of oxygen-carrying capacity.

Oxygen-carrying capacity of hemocyanin from Limulus and Busycotypus (Busycon) decreases with increasing radiation, giving initial yield values for G(-O(2),) of 1.1 and 1.0, respectively. High radiation doses regenerate this capacity of Busycotypus hemocyanin. These effects are attributed largely to the dual nature of hydrogen peroxide, which, at low concentrations, oxidizes protein-bound copper and at high concentrations, that is, at high doses, reduces oxidized copper. The ability of hemocyanin to decompose hydrogen peroxide is relatively unaffected by irradiation, which suggests that copper atoms at the active sites are not all equivalent. The catalase-like activity of Busycotypus hemocyanin can be simulated by amino acid chelates of copper, including arginine, histidine, and glycine.

High tunability of the soft mode in strained SrTiO(3)/DyScO(3) multilayers.

SrTiO(3)/DyScO(3) epitaxial multilayers with variable number and thickness (10-100 nm) of bilayers deposited on DyScO(3) substrates were investigated by means of time-domain terahertz spectroscopy at room temperature. A tensile strain develops in the SrTiO(3) films and shifts the eigenfrequency of the ferroelectric soft mode down by ∼25-45 cm(-1) with respect to the value found for single crystals. In all films the soft mode strongly hardens upon the electrical bias and a linear coupling to a silent excitation of relaxation type at 10 cm(-1) is observed. We show that the change in the THz and sub-THz response of the layers with an increasing field is determined solely by the soft mode eigenfrequency and we propose a phenomenological model describing the origin of the tunability and the peculiar properties of the ferroelectric soft mode in the terahertz spectral range.

[Tumor profiling of renal cell tumors: relevance for diagnostics and therapy]. / Molekulares Tumorprofiling von Nierenzelltumoren: Relevanz für Diagnostik und Therapie.

Molecular biological tumor markers and prognostic parameters are necessary for differential diagnosis, individual prognosis, and therapy in patients with renal cell tumors. By using high throughput technologies, it is possible to characterize tumor samples comprehensively. Based on specific genetic alterations, histopathological subtypes were defined as independent tumor entities. Genetic characteristics can be used for diagnosis of primary tumor samples and also of biopsies. Furthermore, specific molecular patterns of metastatic tumors are known, allowing the determination of the primary tumor's metastatic potential. The specific protein patterns of serum samples of tumor patients were analyzed, and several candidate proteins have been identified. One of these is SAA-1, which is elevated in patients with clear cell renal cell carcinomas (RCC). New therapeutic options are now available for patients with metastatic RCC. Therefore, it is necessary to select the best therapy for each patient and to detect therapy resistance very early. Biomarkers in tumor tissue and serum were found to correlate with therapy response.