Universitätspublikationen
Refine
Year of publication
- 2020 (2523) (remove)
Document Type
- Article (1461)
- Doctoral Thesis (233)
- Part of Periodical (215)
- Preprint (172)
- Contribution to a Periodical (140)
- Working Paper (115)
- Book (88)
- Review (58)
- Bachelor Thesis (11)
- Master's Thesis (11)
Language
- English (1724)
- German (767)
- Portuguese (11)
- French (6)
- Spanish (4)
- Italian (3)
- Multiple languages (3)
- slo (3)
- Turkish (2)
Keywords
- Capital Markets Union (25)
- Financial Markets (25)
- Coronavirus (24)
- ECB (24)
- COVID-19 (23)
- inflammation (18)
- SARS-CoV-2 (15)
- coronavirus (15)
- Financial Institutions (13)
- Banking Regulation (12)
Institute
- Medizin (742)
- Präsidium (278)
- Physik (269)
- Wirtschaftswissenschaften (216)
- Sustainable Architecture for Finance in Europe (SAFE) (167)
- Biowissenschaften (159)
- Frankfurt Institute for Advanced Studies (FIAS) (152)
- Informatik (117)
- Biochemie, Chemie und Pharmazie (104)
- Neuere Philologien (95)
Central banks unexpectedly tightening policy rates often observe the exchange value of their currency depreciate, rather than appreciate as predicted by standard models. We document this for Fed and ECB policy days using event studies and ask whether an information effect, where the public attributes the policy surprise to an unobserved state of the economy that the central bank is signaling by its policy may explain the abnormality. It turns out that many informational assumptions make a standard two- country New Keynesian model match this behavior. To identify the particular mechanism, we condition on multiple asset prices in the event study and model implications for these. We find that there is heterogeneity in this dimension in the event study and no model with a single regime can match the evidence. Further, even after conditioning on possible information effects driving longer term interest rates, there appear to be other drivers of exchange rates. Our results show that existing models have a long way to go in reconciling event study analysis with model-based mechanisms of asset pricing.
Background & Aims: NAFLD is a growing health concern. The aim of the Fatty Liver Assessment in Germany (FLAG) study was to assess disease burden and provide data on the standard of care from secondary care. Methods: The FLAG study is an observational real-world study in patients with NAFLD enrolled at 13 centres across Germany. Severity of disease was assessed by non-invasive surrogate scores and data recorded at baseline and 12 months. Results: In this study, 507 patients (mean age 53 years; 47% women) were enrolled. According to fibrosis-4 index, 64%, 26%, and 10% of the patients had no significant fibrosis, indeterminate stage, and advanced fibrosis, respectively. Patients with advanced fibrosis were older, had higher waist circumferences, and higher aspartate aminotransferase and gamma-glutamyltransferase as well as ferritin levels. The prevalence of obesity, arterial hypertension, and type 2 diabetes increased with fibrosis stages. Standard of care included physical exercise >2 times per week in 17% (no significant fibrosis), 19% (indeterminate), and 6% (advanced fibrosis) of patients. Medication with either vitamin E, silymarin, or ursodeoxycholic acid was reported in 5%. Approximately 25% of the patients received nutritional counselling. According to the FibroScan-AST score, 17% of patients presented with progressive non-alcoholic steatohepatitis (n = 107). On follow-up at year 1 (n = 117), weight loss occurred in 47% of patients, of whom 17% lost more than 5% of body weight. In the weight loss group, alanine aminotransferase activities were reduced by 20%. Conclusions: This is the first report on NAFLD from a secondary-care real-world cohort in Germany. Every 10th patient presented with advanced fibrosis at baseline. Management consisted of best supportive care and lifestyle recommendations. The data highlight the urgent need for systematic health agenda in NAFLD patients. Lay summary: FLAG is a real-world cohort study that examined the liver disease burden in secondary and tertiary care. Herein, 10% of patients referred to secondary care for NAFLD exhibited advanced liver disease, whilst 64% had no significant liver scarring. These findings underline the urgent need to define patient referral pathways for suspected liver disease.
This article discusses the potential of a historical approach to sustainability transformations. Using environmental issues and governance structures as case studies, it first describes how historical “sustainability transformations” can be conceptualized. It then suggests that 19th-century constitutional reforms can be read as attempts at reaching fiscal sustainability, whereas some social reforms can be interpreted as attempts to render the capitalist economy sustainable. In conclusion, the article highlights that the primary value of historical approaches to sustainability transformations will not lie in models, but in encouraging more creative questions.
Primary breast lymphoma accounts for 0.04%-0.5% of all breast malignancies. Primary non-Hodgkin’s lymphomas of the breast are extremely rare and represent approximately 0.38%-0.7% of all cases. Epstein-Barr virus (EBV) has been postulated to play an important role in the pathogenesis of Hodgkin’s lymphoma. We present a case of EBV-positive primary Hodgkin’s lymphoma of the breast. Although there is no sufficient data on this challenging diagnosis, it is known that it could be misdiagnosed with inflammatory breast carcinoma. A crucial part of the proper histopathologic diagnosis is immunohistochemistry. Different modalities of treatment include operative procedure, chemotherapy and radiotherapy. Recent studies suggest chemotherapy and radiotherapy to be initial treatment for patients with primary breast lymphomas.
In the fish embryo toxicity (FET) test with zebrafish (Danio rerio) embryos, 3,4-dichloroaniline (3,4-DCA) is often employed as a positive control substance. Previous studies have characterized bioconcentration and transformation of 3,4-DCA in this test under flow-through conditions. However, the dynamic changes of chemical concentrations in exposure media and embryos were not studied systematically under the commonly used semi-static exposure conditions in multiwell plates. To overcome these limitations, we conducted semi-static exposures experiments where embryolarval zebrafish were exposed to 0.5, 2.0, and 4.0 mg L−1 of 3,4-DCA for up to 120 hpf, with 24-h renewal intervals. During each renewal interval, concentrations of 3,4-DCA were quantified in water samples at 0, 6, 18, and 24 h using high-performance liquid chromatography with diode array detection. Levels of 3,4-DCA in larvae were measured after 120 h exposure. Concentrations of 3,4-DCA in the test vessels decreased rapidly during exposure. Taking these dynamics into account, bioconcentration factors in the present study ranged from 12.9 to 29.8 L kg−1, depending on exposure concentration. In summary, this study contributed to our knowledge of chemical dynamics in the FET test with embryolarval zebrafish, which will aid in defining suitable exposure conditions for future studies.
Drug resistance of childhood cancer neuroblastoma is a serious clinical problem. Patients with relapsed disease have a poor prognosis despite intense treatment. In the present study, we aimed to identify chemoresistance gene expression signatures in vincristine resistant neuroblastoma cells. We found that vincristine-resistant neuroblastoma cells formed larger clones and survived under reduced serum conditions as compared with non-resistant parental cells. To identify the possible mechanisms underlying vincristine resistance in neuroblastoma cells, we investigated the expression profiles of genes known to be involved in cancer drug resistance. This specific gene expression patterns could predict the behavior of a tumor in response to chemotherapy and for predicting the prognosis of high-risk neuroblastoma patients. Our signature could help chemoresistant neuroblastoma patients in avoiding useless and harmful chemotherapy cycles.
Our primary objective is to construct a plausible, unified model of inflation, dark energy and dark matter from a fundamental Lagrangian action first principle, wherein all fundamental ingredients are systematically dynamically generated starting from a very simple model of modified gravity interacting with a single scalar field employing the formalism of non-Riemannian spacetime volume-elements. The non-Riemannian volume element in the initial scalar field action leads to a hidden, nonlinear Noether symmetry which produces an energy-momentum tensor identified as the sum of a dynamically generated cosmological constant and dust-like dark matter. The non-Riemannian volume-element in the initial Einstein–Hilbert action upon passage to the physical Einstein-frame creates, dynamically, a second scalar field with a non-trivial inflationary potential and with an additional interaction with the dynamically generated dark matter. The resulting Einstein-frame action describes a fully dynamically generated inflationary model coupled to dark matter. Numerical results for observables such as the scalar power spectral index and the tensor-to-scalar ratio conform to the latest 2018 PLANCK data.
Our knowledge of early evolution of snakes is improving, but all that we can infer about the evolution of modern clades of snakes such as boas (Booidea) is still based on isolated bones. Here, we resolve the phylogenetic relationships of Eoconstrictor fischeri comb. nov. and other booids from the early-middle Eocene of Messel (Germany), the best-known fossil snake assemblage yet discovered. Our combined analyses demonstrate an affinity of Eoconstrictor with Neotropical boas, thus entailing a South America-to-Europe dispersal event. Other booid species from Messel are related to different New World clades, reinforcing the cosmopolitan nature of the Messel booid fauna. Our analyses indicate that Eoconstrictor was a terrestrial, medium- to large-bodied snake that bore labial pit organs in the upper jaw, the earliest evidence that the visual system in snakes incorporated the infrared spectrum. Evaluation of the known palaeobiology of Eoconstrictor provides no evidence that pit organs played a role in the predator–prey relations of this stem boid. At the same time, the morphological diversity of Messel booids reflects the occupation of several terrestrial macrohabitats, and even in the earliest booid community the relation between pit organs and body size is similar to that seen in booids today.
Fifty years ago, Zajonc, Heingartner, and Herman (1969) conducted a famous experiment on social enhancement and inhibition of performance in cockroaches. A moderating effect of task difficulty on the effect of the presence of an audience, as revealed by impaired performance in complex tasks and enhanced performance in simple tasks, was presented as the major conclusion of this research. However, the researchers did not test this interaction statistically. We conducted a preregistered direct replication using a 2 (audience: present vs. absent) × 2 (task difficulty: runway vs. maze) between-subjects design. Results revealed main effects for task difficulty, with faster running times in the runway than the maze, and for audience, with slower running times when the audience was present than when it was absent. There was no interaction between the presence of an audience and task difficulty. Although we replicated the social-inhibition effect, there was no evidence for a social-facilitation effect.
Ein halbes Jahrhundert Judaistik in Frankfurt : das »kleine Fach« feiert 50-jähriges Bestehen
(2020)
Predictability and the cross-section of expected returns: a challenge for asset pricing models
(2020)
Many modern macro finance models imply that excess returns on arbitrary assets are predictable via the price-dividend ratio and the variance risk premium of the aggregate stock market. We propose a simple empirical test for the ability of such a model to explain the cross-section of expected returns by sorting stocks based on the sensitivity of expected returns to these quantities. Models with only one uncertainty-related state variable, like the habit model or the long-run risks model, cannot pass this test. However, even extensions with more state variables mostly fail. We derive criteria models have to satisfy to produce expected return patterns in line with the data and discuss various examples.
The possibility to investigate the impact of news on stock prices has observed a strong evolution thanks to the recent use of natural language processing (NLP) in finance and economics. In this paper, we investigate COVID-19 news, elaborated with the ”Natural Language Toolkit” that uses machine learning models to extract the news’ sentiment. We consider the period from January till June 2020 and analyze 203,886 online articles that deal with the pandemic and that were published on three platforms: MarketWatch.com, Reuters.com and NYtimes.com. Our findings show that there is a significant and positive relationship between sentiment score and market returns. This result indicates that an increase (decrease) in the sentiment score implies a rise in positive (negative) news and corresponds to positive (negative) market returns. We also find that the variance of the sentiments and the volume of the news sources for Reuters and MarketWatch, respectively, are negatively associated to market returns indicating that an increase of the uncertainty of the sentiment and an increase in the arrival of news have an adverse impact on the stock market.
This article discusses the counterpart of interactive machine learning, i.e., human learning while being in the loop in a human-machine collaboration. For such cases we propose the use of a Contradiction Matrix to assess the overlap and the contradictions of human and machine predictions. We show in a small-scaled user study with experts in the area of pneumology (1) that machine-learning based systems can classify X-rays with respect to diseases with a meaningful accuracy, (2) humans partly use contradictions to reconsider their initial diagnosis, and (3) that this leads to a higher overlap between human and machine diagnoses at the end of the collaboration situation. We argue that disclosure of information on diagnosis uncertainty can be beneficial to make the human expert reconsider her or his initial assessment which may ultimately result in a deliberate agreement. In the light of the observations from our project, it becomes apparent that collaborative learning in such a human-in-the-loop scenario could lead to mutual benefits for both human learning and interactive machine learning. Bearing the differences in reasoning and learning processes of humans and intelligent systems in mind, we argue that interdisciplinary research teams have the best chances at tackling this undertaking and generating valuable insights.
Using experimental data from a comprehensive field study, we explore the causal effects of algorithmic discrimination on economic efficiency and social welfare. We harness economic, game-theoretic, and state-of-the-art machine learning concepts allowing us to overcome the central challenge of missing counterfactuals, which generally impedes assessing economic downstream consequences of algorithmic discrimination. This way, we are able to precisely quantify downstream efficiency and welfare ramifications, which provides us a unique opportunity to assess whether the introduction of an AI system is actually desirable. Our results highlight that AI systems’ capabilities in enhancing welfare critically depends on the degree of inherent algorithmic biases. While an unbiased system in our setting outperforms humans and creates substantial welfare gains, the positive impact steadily decreases and ultimately reverses the more biased an AI system becomes. We show that this relation is particularly concerning in selective-labels environments, i.e., settings where outcomes are only observed if decision-makers take a particular action so that the data is selectively labeled, because commonly used technical performance metrics like the precision measure are prone to be deceptive. Finally, our results depict that continued learning, by creating feedback loops, can remedy algorithmic discrimination and associated negative effects over time.
In this paper we adopt the Hamiltonian Monte Carlo (HMC) estimator for DSGE models by implementing it into a state-of-the-art, freely available high-performance software package. We estimate a small scale textbook New-Keynesian model and the Smets-Wouters model on US data. Our results and sampling diagnostics confirm the parameter estimates available in existing literature. In addition we combine the HMC framework with the Sequential Monte Carlo (SMC) algorithm which permits the estimation of DSGE models with ill-behaved posterior densities.
Background: Posttraumatic stress disorder (PTSD) is one of the psychopathological consequences of sexual and/or physical abuse. The economic burden is assumed to be high, whereas health-related quality of life and education is negatively affected. This study aims to determine health care costs, health-related quality of life, and educational interruption in adolescents and young adults with PTSD after sexual and/or physical abuse in Germany.
Methods: This analysis used data of 87 participants aged 14–21 years of a randomized controlled trial. Health care utilization, health-related quality of life (EQ-5D-5L), sick leave days, productivity, and delay or failure to achieve educational aims were assessed. Health care costs from a payer perspective were calculated using unit costs for the year 2014.
Results: Mean health care costs for a six-month period were 5,243€ (SE 868€). In particular, costs of inpatient stays in psychiatric hospitals, general hospitals and rehabilitation as well as child welfare institutions were high. In addition, health-related quality of life was lower due to anxiety/depression, resulting in a mean EQ-5D index and EQ-VAS score of 0.70 and 61.0, respectively. Furthermore, participants reported on average 27 sick leave days, a productivity loss of 61%, and a delay in education attainment as well as having been unable to achieve educational aims.
Conclusion: PTSD in adolescents and young adults is associated with a high economic burden. Health-related quality of life was substantially reduced. Furthermore, delay and productivity losses in education were observed.
Clinical Trial Registration: German Clinical Trials Register identifier: DRKS00004787; date of registration: 18th March 2013; https://www.drks.de.
Previous studies in developing Xenopus and zebrafish reported that the phosphate transporter slc20a1a is expressed in pronephric kidneys. The recent identification of SLC20A1 as a monoallelic candidate gene for cloacal exstrophy further suggests its involvement in the urinary tract and urorectal development. However, little is known of the functional role of SLC20A1 in urinary tract development. Here, we investigated this using morpholino oligonucleotide knockdown of the zebrafish ortholog slc20a1a. This caused kidney cysts and malformations of the cloaca. Moreover, in morphants we demonstrated dysfunctional voiding and hindgut opening defects mimicking imperforate anus in human cloacal exstrophy. Furthermore, we performed immunohistochemistry of an unaffected 6-week-old human embryo and detected SLC20A1 in the urinary tract and the abdominal midline, structures implicated in the pathogenesis of cloacal exstrophy. Additionally, we resequenced SLC20A1 in 690 individuals with bladder exstrophy-epispadias complex (BEEC) including 84 individuals with cloacal exstrophy. We identified two additional monoallelic de novo variants. One was identified in a case-parent trio with classic bladder exstrophy, and one additional novel de novo variant was detected in an affected mother who transmitted this variant to her affected son. To study the potential cellular impact of SLC20A1 variants, we expressed them in HEK293 cells. Here, phosphate transport was not compromised, suggesting that it is not a disease mechanism. However, there was a tendency for lower levels of cleaved caspase-3, perhaps implicating apoptosis pathways in the disease. Our results suggest SLC20A1 is involved in urinary tract and urorectal development and implicate SLC20A1 as a disease-gene for BEEC.
We estimate the feeddown contributions from decays of unstable A=4 and A=5 nuclei to the final yields of protons, deuterons, tritons, 3He, and 4He produced in relativistic heavy-ion collisions at sNN>2.4 GeV, using the statistical model. The feeddown contribution effects do not exceed 5% at LHC and top RHIC energies due to the large penalty factors involved, but are substantial at intermediate collision energies. We observe large feeddown contributions for tritons, 3He, and 4He at sNN≲10 GeV, where they may account for as much as 70% of the final yield at the lower end of the collision energies considered. Sizable (>10%) effects for deuteron yields are observed at sNN≲4 GeV. The results suggest that the excited nuclei feeddown cannot be neglected in the ongoing and future analysis of light nuclei production at intermediate collision energies, including HADES and CBM experiments at FAIR, NICA at JINR, RHIC beam energy scan and fixed-target programmes, and NA61/SHINE at CERN. We further show that the freeze-out curve in the T-μB plane itself is affected significantly by the light nuclei at high baryochemical potential.
In this paper, we discuss the damping of density oscillations in dense nuclear matter in the temperature range relevant to neutron star mergers. This damping is due to bulk viscosity arising from the weak interaction “Urca” processes of neutron decay and electron capture. The nuclear matter is modelled in the relativistic density functional approach. The bulk viscosity reaches a resonant maximum close to the neutrino trapping temperature, then drops rapidly as temperature rises into the range where neutrinos are trapped in neutron stars. We investigate the bulk viscous dissipation timescales in a post-merger object and identify regimes where these timescales are as short as the characteristic timescale ∼10 ms, and, therefore, might affect the evolution of the post-merger object. Our analysis indicates that bulk viscous damping would be important at not too high temperatures of the order of a few MeV and densities up to a few times saturation density.
This article elucidates the spatial order that underpins the politics of the Anthropocene – the ecological nomos of the earth – and criticizes its imperial origins and legacies. It provides a critical reading of Carl Schmitt’s spatial thought to not only illuminate the spatio-political ontology but also the violence and usurpations that characterize the Anthropocene condition. The article first shows how with the emergence of the ecological nomos seemingly ‘natural’ spaces like the biosphere and the atmosphere became politically charged. This challenges the modernist separation between natural facts and political norms. It then underlines the imperial origins of this nomos by introducing the concept of air-appropriation understood as the colonization of atmospheric space by CO2 emissions. Instead of assuming that the ecological nomos represents a transition from a colonial to an ecological and cosmopolitan world order, focusing on air-appropriation highlights forms of ecological imperialism that go along with the new nomos. Accordingly, the article calls for a just redistribution of ecospace that takes into account the imperial legacies and ongoing effects of air-appropriation.
Objective: To determine the impact of an exercise-based prehabilitation (EBPrehab) program on preand postoperative exercise capacity, functional capacity (FC) and quality of life (QoL) in patients awaiting elective coronary artery bypass graft surgery (CABG).
Design: A two-group randomized controlled trail.
Setting: Ambulatory prehabilitation.
Subjects: Overall 230 preoperative elective CABG-surgery patients were randomly assigned to an intervention (IG, n=88; n=27 withdrew after randomization) or control group (CG, n=115).
Intervention: IG: two-week EBPrehab including supervised aerobic exercise. CG: usual care.
Main measures: At baseline (T1), one day before surgery (T2), at the beginning (T3) and at the end of cardiac rehabilitation (T4) the following measurements were performed: cardiopulmonary exercise test, six-minute walk test (6MWT), Timed-Up-and-Go Test (TUG) and QoL (MacNew questionnaire).
Results: A total of 171 patients (IG, n=81; CG, n=90) completed the study. During EBPrehab no complications occurred. Preoperatively FC (6MWTIG: 443.0±80.1m to 493.5±75.5m, P=0.003; TUGIG: 6.9±2.0 s to 6.1±1.8 s, P=0.018) and QoL (IG: 5.1±0.9 to 5.4±0.9, P<0.001) improved significantly more in IG compared to CG. Similar effects were observed postoperatively in FC (6MWDIG: Δ-64.7m, pT1–T3=0.013; Δ+47.2m, pT1–T4<0.001; TUGIG: Δ+1.4s, pT1–T3=0.003).
Conclusions: A short-term EBPrehab is effective to improve perioperative FC and preoperative QoL in patients with stable coronary artery disease awaiting CABG-surgery.
Simple Summary
The interaction between tumors and immune cells influences tumor fate, i.e., regression, growth, or even metastases. The evaluation of tumor infiltrating lymphocytes (TILs) in human breast cancer has prognostic value. Pet rabbits develop spontaneous mammary carcinomas and have an immune system that is comparable with that of humans, so that they have the potential to provide an animal model for human breast cancer. To further substantiate this similarity, this study examined TILs in 107 pet rabbit mammary carcinomas according to criteria established for human breast cancer. For TIL evaluation routinely stained microscopic sections were examined by light microscopy. Relevant histological and immunohistochemical tumor characteristics were obtained from a data base. Results showed that increased presence of stromal TILs was statistically associated with histological tumor features indicative of a less aggressive biological behavior, i.e., reduced tumor cell proliferation and a lower histological grade. The expression by tumor cells of calponin, a presumed tumor suppressor protein, was also associated with their reduced proliferation and a higher percentage of stromal TILs. Data suggest that higher percentages of stromal TILs may have the potential to serve as favorable prognostic indicator in rabbit mammary carcinomas and support the value of pet rabbits for comparative research.
Abstract
Tumor infiltrating lymphocytes (TILs) serve as prognostic biomarker in human breast cancer. Rabbits have the potential to act as animal model for human breast cancer, and close similarities exist between the rabbit and human immune system. The aim of this study is to characterize TILs in pet rabbit mammary carcinomas and to statistically correlate results with histological and immunohistochemical tumor characteristics. Microscopic evaluation of TILs was performed in hematoxylin and eosin stained sections of 107 rabbit mammary carcinomas according to international guidelines for human breast cancer. Data on histological features of malignancy, estrogen and progesterone receptor status and calponin expression were obtained from the data base. This study revealed a statistical association between stromal TILs in the central tumor (CT) and infiltrative margin. Higher maximal percentages of stromal TILs at the CT were statistically correlated with decreased mitotic count and lower tumor grade. An increased number of calponin positive tumor cells was statistically associated with a lower mitotic count and a higher percentage of stromal TILs. Results suggest that higher percentages of stromal TILs are useful biomarkers that may point toward a favorable prognosis in rabbit mammary carcinomas and support the concept of the use of rabbits for translational research
Degeneration of neurons, such as the inner ear spiral ganglion neurons (SGN), may be decelerated or even stopped by neurotrophic factor treatment, such as brain-derived neurotrophic factor (BDNF), as well as electrical stimulation (ES). In a clinical setting, drug treatment of the SGN could start directly during implantation of a cochlear implant, whereas electrical stimulation begins days to weeks later. The present study was conducted to determine the effects of consecutive BDNF and ES treatments on SGN density and electrical responsiveness. An electrode drug delivery device was implanted in guinea pigs 3 weeks after deafening and five experimental groups were established: two groups received intracochlear infusion of artificial perilymph (AP) or BDNF; two groups were treated with AP respectively BDNF in addition to ES (AP + ES, BDNF + ES); and one group received BDNF from the day of implantation until day 34 followed by ES (BDNF ⇨ ES). Electrically evoked auditory brainstem responses were recorded. After one month of treatment, the tissue was harvested and the SGN density was assessed. The results show that consecutive treatment with BDNF and ES was as successful as the simultaneous combined treatment in terms of enhanced SGN density compared to the untreated contralateral side but not in regard to the numbers of protected cells.
Workaholism and overcommitment are often used as interchangeable constructs describing an individual’s over-involvement toward their own job. Employees with high levels in both constructs are characterized by an excessive effort and attachment to their job, with the incapability to detach from it and negative consequences in terms of poor health and job burnout. However, few studies have simultaneously measured both constructs, and their relationships are still not clear. In this study, we try to disentangle workaholism and overcommitment by comparing them with theoretically related contextual and personal antecedents, as well as their health consequences. We conducted a nonprobability mixed mode research design on 133 employees from different organizations in Italy using both self- and other-reported measures. To test our hypothesis that workaholism and overcommitment are related yet different constructs, we used partial correlations and regression analyses. The results confirm that these two constructs are related to each other, but also outline that overcommitment (and not workaholism) is uniquely related to job burnout, so that overcommitment rather than workaholism could represent the true negative aspect of work drive. Additionally, workaholism is more related to conscientiousness than overcommitment, while overcommitment shows a stronger relationship with neuroticism than workaholism. The theoretical implications are discussed.
This paper provides new geochemical data focusing on valuable elements in the coal, parting, and floor samples in the No. 5 coal seam of the Taiyuan Formation from the Wujiawan mine, Datong coalfield, northern China. The minerals mainly consist of kaolinite, calcite, and pyrite, as well as trace amounts of quartz and illite. The No. 5 coal is enriched in Li, Ga, high field strength elements (HFSEs), and rare earth elements and yttrium (REY) when compared with world hard coals. Of particular interest is the high average concentration of Li (67.66 μg/g), which is around seven times higher than the value for world hard coals. Lithium, Ga, and HFSEs have strong inorganic affinities, whereas REY have organic affinities. The main carrier of Li, Ga, and HFSEs is aluminosilicate minerals, while REY appear to occur with organophosphorus. These HFSEs are enriched, both in the parting and in the adjacent coal samples. This suggests that these elements are likely to leach out during the diagenetic process. The distribution patterns of REY, along with the ratio of Al2O3/TiO2 and the figure of Zr/TiO2 vs. Nb/Y are suggestive of their derivation from felsic parent material. In the northern and eastern part of the Datong coalfield, there are several regions where the Li content is higher than the mineable grade, in particular in the northern Datong coalfield where there is a mine with an Li content of 294.6 μg/g. This is significantly higher than the mineable grade. Therefore, there is a potential for financially viable recovery of Li in these coals of the Datong coalfield.
Virtual reality (VR) headsets offer a large and immersive workspace for displaying visualizations with stereoscopic vision, as compared to traditional environments with monitors or printouts. The controllers for these devices further allow direct three-dimensional interaction with the virtual environment. In this paper, we make use of these advantages to implement a novel multiple and coordinated view (MCV) system in the form of a vertical stack, showing tilted layers of geospatial data. In a formal study based on a use-case from urbanism that requires cross-referencing four layers of geospatial urban data, we compared it against more conventional systems similarly implemented in VR: a simpler grid of layers, and one map that allows for switching between layers. Performance and oculometric analyses showed a slight advantage of the two spatial-multiplexing methods (the grid or the stack) over the temporal multiplexing in blitting. Subgrouping the participants based on their preferences, characteristics, and behavior allowed a more nuanced analysis, allowing us to establish links between e.g., saccadic information, experience with video games, and preferred system. In conclusion, we found that none of the three systems are optimal and a choice of different MCV systems should be provided in order to optimally engage users.
The morbidity and mortality of severely injured patients are commonly affected by multiple factors. Especially, severe chest trauma has been shown to be a significant factor in considering outcome. Contemporaneously, weight-associated endocrinological, haematological, and metabolic deviations from the norm seem to have an impact on the posttraumatic course. Therefore, the aim of this study was to determine the influence of body weight on severely injured patients by emphasizing chest trauma. A total of 338 severely injured patients were included. Multivariate regression analyses were performed on patients with severe chest trauma (AIS ≥ 3) and patients with minor chest trauma (AIS < 3). The influence of body weight on in-hospital mortality was evaluated. Of all the patients, 70.4% were male, the median age was 52 years (IQR 36–68), the overall Injury Severity Score (ISS) was 24 points (IQR 17–29), and a median BMI of 25.1 points (IQR 23–28) was determined. In general, chest trauma was associated with prolonged ventilation, prolonged ICU treatment, and increased mortality. For overweight patients with severe chest trauma, an independent survival benefit was found (OR 0.158; p = 0.037). Overweight seems to have an impact on the mortality of severely injured patients with combined chest trauma. Potentially, a nutritive advantage or still-unknown immunological aspects in these patients affecting the intensive treatment course could be argued.
Focused electron beam induced deposition (FEBID) is a direct-write nanofabrication technique able to pattern three-dimensional magnetic nanostructures at resolutions comparable to the characteristic magnetic length scales. FEBID is thus a powerful tool for 3D nanomagnetism which enables unique fundamental studies involving complex 3D geometries, as well as nano-prototyping and specialized applications compatible with low throughputs. In this focused review, we discuss recent developments of this technique for applications in 3D nanomagnetism, namely the substantial progress on FEBID computational methods, and new routes followed to tune the magnetic properties of ferromagnetic FEBID materials. We also review a selection of recent works involving FEBID 3D nanostructures in areas such as scanning probe microscopy sensing, magnetic frustration phenomena, curvilinear magnetism, magnonics and fluxonics, offering a wide perspective of the important role FEBID is likely to have in the coming years in the study of new phenomena involving 3D magnetic nanostructures.
Importance Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide. Case reports of hospitalized patients suggest that COVID-19 prominently affects the cardiovascular system, but the overall impact remains unknown.
Objective To evaluate the presence of myocardial injury in unselected patients recently recovered from COVID-19 illness.
Design, Setting, and Participants In this prospective observational cohort study, 100 patients recently recovered from COVID-19 illness were identified from the University Hospital Frankfurt COVID-19 Registry between April and June 2020.
Exposure Recent recovery from severe acute respiratory syndrome coronavirus 2 infection, as determined by reverse transcription–polymerase chain reaction on swab test of the upper respiratory tract.
Main Outcomes and Measures Demographic characteristics, cardiac blood markers, and cardiovascular magnetic resonance (CMR) imaging were obtained. Comparisons were made with age-matched and sex-matched control groups of healthy volunteers (n = 50) and risk factor–matched patients (n = 57).
Results Of the 100 included patients, 53 (53%) were male, and the mean (SD) age was 49 (14) years. The median (IQR) time interval between COVID-19 diagnosis and CMR was 71 (64-92) days. Of the 100 patients recently recovered from COVID-19, 67 (67%) recovered at home, while 33 (33%) required hospitalization. At the time of CMR, high-sensitivity troponin T (hsTnT) was detectable (greater than 3 pg/mL) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (greater than 13.9 pg/mL) in 5 patients (5%). Compared with healthy controls and risk factor–matched controls, patients recently recovered from COVID-19 had lower left ventricular ejection fraction, higher left ventricle volumes, and raised native T1 and T2. A total of 78 patients recently recovered from COVID-19 (78%) had abnormal CMR findings, including raised myocardial native T1 (n = 73), raised myocardial native T2 (n = 60), myocardial late gadolinium enhancement (n = 32), or pericardial enhancement (n = 22). There was a small but significant difference between patients who recovered at home vs in the hospital for native T1 mapping (median [IQR], 1119 [1092-1150] ms vs 1141 [1121-1175] ms; P = .008) and hsTnT (4.2 [3.0-5.9] pg/dL vs 6.3 [3.4-7.9] pg/dL; P = .002) but not for native T2 mapping. None of these measures were correlated with time from COVID-19 diagnosis (native T1: r = 0.07; P = .47; native T2: r = 0.14; P = .15; hsTnT: r = −0.07; P = .50). High-sensitivity troponin T was significantly correlated with native T1 mapping (r = 0.33; P < .001) and native T2 mapping (r = 0.18; P = .01). Endomyocardial biopsy in patients with severe findings revealed active lymphocytic inflammation. Native T1 and T2 were the measures with the best discriminatory ability to detect COVID-19–related myocardial pathology.
Conclusions and Relevance In this study of a cohort of German patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis. These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.
Aortic stenosis is the most common valvular disease worldwide. With transcatheter aortic valve replacement (TAVR) being increasingly expanded to lower-risk populations, several challenging issues remain to be solved. The present review aims at discussing modern approaches to such issues as well as the current status of TAVR. TAVR has undergone several developments in the recent years: an increased use of transfemoral access, the development of prostheses in order to adapt to challenging anatomies, improved delivery systems with repositioning features, and outer skirts aiming at reducing paravalvular leak. The indication of TAVR is increasingly being expanded to patients with lower surgical risk. The main clinical trials supporting such expansion are reviewed and the latest data on low-risk patients are discussed. A number of challenges need still to be addressed and are also reviewed in this paper: the need for updated international guidelines including the latest evidence; a reduction of main complications such as permanent pacemaker implantation, paravalvular leak, and stroke (and its potential prevention by using anti-embolic protection devices); the appropriate role of TAVR in patients with concomitant cardiac ischemic disease; and durability of bio-prosthetic implanted valves. Finally, the future perspectives for TAVR use and next device developments are discussed.
Background: Aortic stenosis (AS) is the most prevalent primary heart valve disease and the third most prevalent cardiovascular disease in the world, having a severe and slowly progressive evolution. The implementation of Transcatheter Aortic Valve Implantation (TAVI) is necessary because the population is constantly ageing, and most elderly people have various comorbidities, which places them among patients with high surgical risk. The aim was to report immediate and 9 months follow-up results of first TAVI implantations in the Republic of Moldova.
Material and methods: Three patients with severe symptomatic AS and high surgical risk underwent TAVI implantation using Portico valves.
Results: The mean age was 76.7 ± 1.2 years, 2 women and 1 man. The mean Logistic EuroSCORE II was 5.68 ± 0.67%. Procedural success was achieved in all (100%) patients. After the intervention, it was shown that the GP mean decreased by an average of 20.27±1.61 mmHg, the Vmax of the jet through AoV decreased on average by 2.05±0.19 m/s, and they were maintained all over the nine months follow-up period. Quality of life, using the TASQ (Toronto Aortic Stenosis Quality of Life) questionnaire, was improved by 62.3 ± 2.2 points.
Conclusions: TAVI, as a new minimally invasive method of treatment for aortic valve stenosis appears to be safe, with a low rate of early and late complications in elderly patients at high surgical risk, with good clinical outcomes at 9 months. Its implementation in the Republic of Moldova is welcome in the conditions of continuously ageing population and the prevalence of associated comorbidities.
Relapsing fever (RF) is claimed a neglected arthropod-borne disease caused by a number of diverse human pathogenic Borrelia (B.) species. These RF borreliae are separated into the groups of tick-transmitted species including B. duttonii, B. hermsii, B. parkeri, B. turicatae, B. hispanica, B. persica, B. caucasica, and B. myiamotoi, and the louse-borne Borrelia species B. recurrentis. As typical blood-borne pathogens achieving high cell concentrations in human blood, RF borreliae (RFB) must outwit innate immunity, in particular complement as the first line of defense. One prominent strategy developed by RFB to evade innate immunity involves inactivation of complement by recruiting distinct complement regulatory proteins, e.g., C1 esterase inhibitor (C1-INH), C4b-binding protein (C4BP), factor H (FH), FH-like protein-1 (FHL-1), and factor H-related proteins FHR-1 and FHR-2, or binding of individual complement components and plasminogen, respectively. A number of multi-functional, complement and plasminogen-binding molecules from distinct Borrelia species have previously been identified and characterized, exhibiting considerable heterogeneity in their sequences, structures, gene localization, and their capacity to bind host-derived proteins. In addition, RFB possess a unique system of antigenic variation, allowing them to change the composition of surface-exposed variable major proteins, thus evading the acquired immune response of the human host. This review focuses on the current knowledge of the immune evasion strategies by RFB and highlights the role of complement-interfering and infection-associated molecules for the pathogenesis of RFB.
Drug resistance is an obstacle in the therapy of acute lymphoblastic leukemia (ALL). Whether the physical properties such as the motility of the cells contribute to the survival of ALL cells after drug treatment has recently been of increasing interest, as they could potentially allow the metastasis of solid tumor cells and the migration of leukemia cells. We hypothesized that chemotherapeutic treatment may alter these physical cellular properties. To investigate the motility of chemotherapeutics-treated B-cell ALL (B-ALL) cells, patient-derived B-ALL cells were treated with chemotherapy for 7 days and left for 12 h without chemotherapeutic treatment. Two parameters of motility were studied, velocity and migration distance, using a time-lapse imaging system. The study revealed that compared to non-chemotherapeutically treated B-ALL cells, B-ALL cells that survived chemotherapy treatment after 7 days showed reduced motility. We had previously shown that Tysabri and P5G10, antibodies against the adhesion molecules integrins α4 and α6, respectively, may overcome drug resistance mediated through leukemia cell adhesion to bone marrow stromal cells. Therefore, we tested the effect of integrin α4 or α6 blockade on the motility of chemotherapeutics-treated ALL cells. Only integrin α4 blockade decreased the motility and velocity of two chemotherapeutics-treated ALL cell lines. Interestingly, integrin α6 blockade did not affect the velocity of chemoresistant ALL cells. This study explores the physical properties of the movements of chemoresistant B-ALL cells and highlights a potential link to integrins. Further studies to investigate the underlying mechanism are warranted.
Psoriasis (PsO) is one of the common chronic inflammatory skin diseases. Approximately 3% of the European Caucasian population is affected. Psoriatic arthritis (PsA) is a chronic immune-mediated disease associated with PsO characterized by distinct musculoskeletal inflammation. Due to its heterogeneous clinical manifestations (e.g., oligo- or polyarthritis, enthesitis, dactylitis, and axial inflammation), early diagnosis of PsA is often difficult and delayed. Approximately 30% of PsO patients will develop PsA. The responsible triggers for the transition from PsO only to PsA are currently unclear, and the impacts of different factors (e.g., genetic, environmental) on disease development are currently discussed. There is a high medical need, recently unmet, to specifically detect those patients with an increased risk for the development of clinically evident PsA early to initiate sufficient treatment to inhibit disease progression and avoid structural damage and loss of function or even intercept disease development. Increased neoangiogenesis and enthesial inflammation are hypothesized to be early pathological findings in PsO patients with PsA development. Different disease states describe the transition from PsO to PsA. Two of those phases are of value for early detection of PsA at-risk patients to prevent later development of PsA as changes in biomarker profiles are detectable: the subclinical phase (soluble and imaging biomarkers detectable, no clinical symptoms) and the prodromal phase (imaging biomarkers detectable, unspecific musculoskeletal symptoms such as arthralgia and fatigue). To target the unmet need for early detection of this at-risk population and to identify the subgroup of patients who will transition from PsO to PsA, imaging plays an important role in characterizing patients precisely. Imaging techniques such as ultrasound (US), magnetic resonance imaging (MRI), and computerized tomography (CT) are advanced techniques to detect sensitively inflammatory changes or changes in bone structure. With the use of these techniques, anatomic structures involved in inflammatory processes can be identified. These techniques are complemented by fluorescence optical imaging as a sensitive method for detection of changes in vascularization, especially in longitudinal measures. Moreover, high-resolution peripheral quantitative CT (HR-pQCT) and dynamic contrast-enhanced MRI (DCE-MRI) may give the advantage to identify PsA-related early characteristics in PsO patients reflecting transition phases of the disease.
Physical activity counseling in primary health care is regarded as a useful complementary preventive and therapeutic measure and is advocated by leading public health institutions. This integrative review summarizes the available data on physical activity counseling in primary care in Germany. A systematic literature search in various databases (peer reviewed and grey literature) was carried out for quantitative and qualitative studies on physical activity counseling and use of “Exercise on Prescription”. The 25 studies included show a very high methodological diversity and, in some cases, considerable risks of bias, with limited comparability across studies. Counseling was provided in all studies by physicians. They report frequent physical activity counseling, which is partly confirmed and partly refuted by patient data. The use of “Exercise on Prescription” is at a very low level. Information on the frequency of physical activity counseling in Germany varies depending on data source and is sometimes contradictory. Our review provides a synthesis of various perspectives on routine physical activity counseling in primary care in Germany. Future studies using standardized and validated instruments in representative samples are needed to further knowledge on counseling and to be able to establish trends in prevalence. Strengthening the topics of physical activity and health and physical activity counseling in medical curriculum is strongly recommended.
Nuclear receptor related 1 (Nurr1) is an orphan ligand-activated transcription factor and considered as neuroprotective transcriptional regulator with great potential as therapeutic target for neurodegenerative diseases. However, the collection of available Nurr1 modulators and mechanistic understanding of Nurr1 are limited. Here, we report the discovery of several structurally diverse non-steroidal anti-inflammatory drugs as inverse Nurr1 agonists demonstrating that Nurr1 activity can be regulated bidirectionally. As chemical tools, these ligands enable unraveling the co-regulatory network of Nurr1 and the mode of action distinguishing agonists from inverse agonists. In addition to its ability to dimerize, we observe an ability of Nurr1 to recruit several canonical nuclear receptor co-regulators in a ligand-dependent fashion. Distinct dimerization states and co-regulator interaction patterns arise as discriminating factors of Nurr1 agonists and inverse agonists. Our results contribute a valuable collection of Nurr1 modulators and relevant mechanistic insights for future Nurr1 target validation and drug discovery.
The coronavirus disease 2019 COVID-19 pandemic is rapidly spreading worldwide and is becoming a major public health crisis. Increasing evidence demonstrates a strong correlation between obesity and the COVID-19 disease. We have summarized recent studies and addressed the impact of obesity on COVID-19 in terms of hospitalization, severity, mortality, and patient outcome. We discuss the potential molecular mechanisms whereby obesity contributes to the pathogenesis of COVID-19. In addition to obesity-related deregulated immune response, chronic inflammation, endothelium imbalance, metabolic dysfunction, and its associated comorbidities, dysfunctional mesenchymal stem cells/adipose-derived mesenchymal stem cells may also play crucial roles in fueling systemic inflammation contributing to the cytokine storm and promoting pulmonary fibrosis causing lung functional failure, characteristic of severe COVID-19. Moreover, obesity may also compromise motile cilia on airway epithelial cells and impair functioning of the mucociliary escalators, reducing the clearance of severe acute respiratory syndrome coronavirus (SARS-CoV-2). Obese diseased adipose tissues overexpress the receptors and proteases for the SARS-CoV-2 entry, implicating its possible roles as virus reservoir and accelerator reinforcing violent systemic inflammation and immune response. Finally, anti-inflammatory cytokines like anti-interleukin 6 and administration of mesenchymal stromal/stem cells may serve as potential immune modulatory therapies for supportively combating COVID-19. Obesity is conversely related to the development of COVID-19 through numerous molecular mechanisms and individuals with obesity belong to the COVID-19-susceptible population requiring more protective measures.
Objective: Spinal epidural abscess (SEA) is a severe and life-threatening disease. Although commonly performed, the effect of timing in surgical treatment on patient outcome is still unclear. With this study, we aim to provide evidence for early surgical treatment in patients with SEA.
Methods: Patients treated for SEA in the authors' department between 2007 and 2016 were included for analysis and retrospectively analyzed for basic clinical parameters and outcome. Pre- and postoperative neurological status were assessed using the American Spinal Injury Association Impairment Scale (AIS). The self-reported quality of life (QOL) based on the Short-Form Health Survey 36 (SF-36) was assessed prospectively. Surgery was defined as "early", when performed within 12 hours after admission and "late" when performed thereafter. Conservative therapy was preferred and recommend in patients without neurological deficits and in patients denying surgical intervention.
Results: One hundred and twenty-three patients were included in this study. Forty-nine patients (39.8%) underwent early, 47 patients (38.2%) delayed surgery and 27 (21.9%) conservative therapy. No significant differences were observed regarding mean age, sex, diabetes, prior history of spinal infection, and bony destruction. Patients undergoing early surgery revealed a significant better clinical outcome before discharge than patients undergoing late surgery (p=0.001) and conservative therapy. QOL based on SF-36 were significantly better in the early surgery cohort in two of four physical items (physical functioning and bodily pain) and in one of four psychological items (role limitation) after a mean follow-up period of 58 months. Readmission to the hospital and failure of conservative therapy were observed more often in patients undergoing conservative therapy.
Conclusion: Our data on both clinical outcome and QOL provide evidence for early surgery within 12 hours after admission in patients with SEA.
Background: The treatment of severely injured patients, especially in older age, is complex, and based on strict guidelines. Methods: We conducted a retrospective study by analyzing our internal registry for mortality risk factors in deceased trauma patients. All patients that were admitted to the trauma bay of our level-1-trauma center from 2014 to 2018, and that died during the in-hospital treatment, were included. The aim of this study was to carry out a quality assurance concerning the initial care of severely injured patients. Results: In the 5-year period, 135 trauma patients died. The median (IQR) age was 69 (38–83) years, 71% were male, and the median (IQR) Injury Severity Score (ISS) was 25 (17–34) points. Overall, 41% of the patients suffered from severe traumatic brain injuries (TBI) (AIShead ≥ 4 points). For 12.7%, therapy was finally limited owing to an existing patient’s decree; in 64.9% with an uncertain prognosis, a ‘therapia minima’ was established in consensus with the relatives. Conclusion: Although the mortality rate was primarily related to the severity of the injury, a significant number of deaths were not exclusively due to medical reasons, but also to a self-determined limitation of therapy for severely injured geriatric patients. The conscientious documentation concerning the will of the patient is increasingly important in supporting medical decisions.
Background: The epidermal growth factor receptor (EGFR) signaling pathway is genetically activated in approximately 50% of glioblastomas (GBs). Its inhibition has been explored clinically but produced disappointing results, potentially due to metabolic effects that protect GB cells against nutrient deprivation and hypoxia. Here, we hypothesized that EGFR activation could disable metabolic adaptation and define a GB cell population sensitive to starvation.
Methods: Using genetically engineered GB cells to model different types of EGFR activation, we analyzed changes in metabolism and cell survival under conditions of the tumor microenvironment.
Results: We found that expression of mutant EGFRvIII as well as EGF stimulation of EGFR-overexpressing cells impaired physiological adaptation to starvation and rendered cells sensitive to hypoxia-induced cell death. This was preceded by adenosine triphosphate (ATP) depletion and an increase in glycolysis. Furthermore, EGFRvIII mutant cells had higher levels of mitochondrial superoxides potentially due to decreased metabolic flux into the serine synthesis pathway which was associated with a decrease in the NADPH/NADP+ ratio.
Conclusions: The finding that EGFR activation renders GB cells susceptible to starvation could help to identify a subgroup of patients more likely to benefit from starvation-inducing therapies.
Background: Unwanted anticholinergic effects are both underestimated and frequently overlooked. Failure to identify adverse drug reactions (ADRs) can lead to prescribing cascades and the unnecessary use of over-thecounter products. The objective of this systematic review and meta-analysis is to explore and quantify the frequency and severity of ADRs associated with amitriptyline vs. placebo in randomized controlled trials (RCTs) involving adults with any indication, as well as healthy individuals. Methods: A systematic search in six electronic databases, forward/backward searches, manual searches, and searches for Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval studies, will be performed. Placebo-controlled RCTs evaluating amitriptyline in any dosage, regardless of indication and without restrictions on the time and language of publication, will be included, as will healthy individuals. Studies of topical amitriptyline, combination therapies, or including <100 participants, will be excluded. Two investigators will screen the studies independently, assess methodological quality, and extract data on design, population, intervention, and outcomes ((non-)anticholinergic ADRs, e.g., symptoms, test results, and adverse drug events (ADEs) such as falls). The primary outcome will be the frequency of anticholinergic ADRs as a binary outcome (absolute number of patients with/without anticholinergic ADRs) in amitriptyline vs. placebo groups. Anticholinergic ADRs will be defined by an experienced clinical pharmacologist, based on literature and data from Martindale: The Complete Drug Reference. Secondary outcomes will be frequency and severity of (non-)anticholinergic ADRs and ADEs. The information will be synthesized in meta-analyses and narratives. We intend to assess heterogeneity using metaregression (for indication, outcome, and time points) and I2 statistics. Binary outcomes will be expressed as odds ratios, and continuous outcomes as standardized mean differences. Effect measures will be provided using 95% confidence intervals. We plan sensitivity analyses to assess methodological quality, outcome reporting etc., and subgroup analyses on age, dosage, and duration of treatment. Discussion: We will quantify the frequency of anticholinergic and other ADRs/ADEs in adults taking amitriptyline for any indication by comparing rates for amitriptyline vs. placebo, hence, preventing bias from disease symptoms and nocebo effects. As no standardized instrument exists to measure it, our overall estimate of anticholinergic ADRs may have limitations.
Background: Essential Tremor (ET) is a progressive neurological disorder characterized by postural and kinetic tremor most commonly affecting the hands and arms. Medically intractable ET can be treated by deep brain stimulation (DBS) of the ventral intermediate nucleus of thalamus (VIM). We investigated whether the location of the effective contact (most tremor suppression with at least side effects) in VIM-DBS for ET changes over time, indicating a distinct mechanism of loss of efficacy that goes beyond progression of tremor severity, or a mere reduction of DBS efficacy.
Methods: We performed programming sessions in 10 patients who underwent bilateral vim-DBS surgery between 2009 and 2017 at our department. In addition to the intraoperative (T1) and first clinical programming session (T2) a third programming session (T3) was performed to assess the effect- and side effect threshold (minimum voltage at which a tremor suppression or side effects occurred). Additionally, we compared the choice of the effective contact between T1 and T2 which might be affected by a surgical induced “brain shift.”
Discussion: Over a time span of about 4 years VIM-DBS in ET showed continuous efficacy in tremor suppression during stim-ON compared to stim-OFF. Compared to immediate postoperative programming sessions in ET-patients with DBS, long-term evaluationshowednorelevantchangeinthechoiceofcontactwithrespecttosideeffects andefficacy.InthemajorityofthecasestheactivecontactatT2didnotcorrespondtothe most effective intraoperative stimulation site T1, which might be explained by a brain-shift due to cerebral spinal fluid loss after neurosurgical procedure.
This case series assessed a commercial airline flight from Tel Aviv, Israel, to Frankfurt, Germany, that occurred on March 9th, 2020. Among 102 passengers on a Boeing 737-900 aircraft were 24 members of a tourist group. Starting 7 days earlier, the group had contact with a hotel manager who later received a diagnosis of coronavirus disease 2019 (COVID-19). No member of the group had received a diagnosis of COVID-19 before the flight, and no measures to prevent transmission (eg, wearing of masks) had been applied. The flight duration was 4 hours 40 minutes.
MicroRNA miR-181 - a rheostat for TCR signaling in thymic selection and peripheral T-Cell function
(2020)
The selection of T cells during intra-thymic d evelopment is crucial to obtain a functional and simultaneously not self-reactive peripheral T cell repertoire. However, selection is a complex process dependent on T cell receptor (TCR) thresholds that remain incompletely understood. In peripheral T cells, activation, clonal expansion, and contraction of the active T cell pool, as well as other processes depend on TCR signal strength. Members of the microRNA (miRNA) miR-181 family have been shown to be dynamically regulated during T cell development as well as dependent on the activation stage of T cells. Indeed, it has been shown that expression of miR-181a leads to the downregulation of multiple phosphatases, implicating miR-181a as ‘‘rheostat’’ of TCR signaling. Consistently, genetic models have revealed an essential role of miR-181a/b-1 for the generation of unconventional T cells as well as a function in tuning TCR sensitivity in peripheral T cells during aging. Here, we review these broad roles of miR-181 family members in T cell function via modulating TCR signal strength.
Physical exercise has been shown to alter sensory functions, such as sensory detection or perceived pain. However, most contributing studies rely on the assessment of single thresholds, and a systematic testing of the sensory system is missing. This randomised, controlled cross-over study aims to determine the sensory phenotype of healthy young participants and to assess if sub-maximal endurance exercise can impact it. We investigated the effects of a single bout of sub-maximal running exercise (30 min at 80% heart rate reserve) compared to a resting control in 20 healthy participants. The sensory profile was assessed applying quantitative sensory testing (QST) according to the protocol of the German Research Network on Neuropathic Pain. QST comprises a broad spectrum of thermal and mechanical detection and pain thresholds. It was applied to the forehead of study participants prior and immediately after the intervention. Time between cross-over sessions was one week. Sub-maximal endurance exercise did not significantly alter thermal or mechanical sensory function (time × group analysis) in terms of detection and pain thresholds. The sensory phenotypes did not indicate any clinically meaningful deviation of sensory function. The alteration of sensory thresholds needs to be carefully interpreted, and only systematic testing allows an improved understanding of mechanism. In this context, sub-maximal endurance exercise is not followed by a change of thermal and mechanical sensory function at the forehead in healthy volunteers.
Atg8-family proteins - structural features and molecular interactions in autophagy and beyond
(2020)
Autophagy is a common name for a number of catabolic processes, which keep the cellular homeostasis by removing damaged and dysfunctional intracellular components. Impairment or misbalance of autophagy can lead to various diseases, such as neurodegeneration, infection diseases, and cancer. A central axis of autophagy is formed along the interactions of autophagy modifiers (Atg8-family proteins) with a variety of their cellular counter partners. Besides autophagy, Atg8-proteins participate in many other pathways, among which membrane trafficking and neuronal signaling are the most known. Despite the fact that autophagy modifiers are well-studied, as the small globular proteins show similarity to ubiquitin on a structural level, the mechanism of their interactions are still not completely understood. A thorough analysis and classification of all known mechanisms of Atg8-protein interactions could shed light on their functioning and connect the pathways involving Atg8-proteins. In this review, we present our views of the key features of the Atg8-proteins and describe the basic principles of their recognition and binding by interaction partners. We discuss affinity and selectivity of their interactions as well as provide perspectives for discovery of new Atg8-interacting proteins and therapeutic approaches to tackle major human diseases.
With obesity having doubled in the last decade, hypertension is on the rise. In one-third of hypertensive patients the metabolic syndrome is present. This might be one factor for the increasing number of prescriptions for angiotensin receptor blockers and calcium-channel blockers besides a more favorable risk-to-benefit ratio. The aim of the present study was to evaluate a therapeutic drug monitoring (TDM) method for assessment of adherence based on cut-offs in inpatients and to compare it to an established urine drug screening in outpatients. A method for quantification of calcium-channel blockers and angiotensin receptor blockers using high-performance liquid chromatography-tandem mass spectrometric analysis (LC-MS/MS) was developed and validated. The method was applied to serum samples of 32 patients under supervised medication to establish cut-off values for adherence assessment based on dose-related concentrations (DRC, calculated from pharmacokinetic data). Furthermore, corresponding urine and blood samples of 42 outpatients without supervised medication were analysed and the results compared with regard to adherence assessment. All serum concentrations measured for amlodipine (n = 40), lercanidipine (n = 14), candesartan (n = 10), telmisartan (n = 4) and valsartan (n = 10) in inpatients were above the patient specific lower DRC confirming adherence. Of 42 outpatients the identification of analytes in urine as well as the quantification in serum exhibited differing results. According to urinalysis, adherence was demonstrated in only 87.0% of prescriptions, compared to 91.3% for serum analyses. Differences were observed for amlodipine, lercanidipine and candesartan which can be explained by a higher specificity of the serum analysis approach due to pharmacokinetics. The present study confirms that assessing adherence based on serum drug concentrations with individually calculated lower DRCs is more accurate than using qualitative urine analysis. In particular, drugs with low bioavailability, low renal excretion or high metabolism rate such as lercanidipine and candesartan may lead to underestimation of adherence via urine analysis.