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Acid sphingomyelinase mediates murine acute lung injury following transfusion of aged platelets
(2017)
Pulmonary complications from stored blood products are the leading cause of mortality related to transfusion. Transfusion-related acute lung injury is mediated by antibodies or bioactive mediators, yet underlying mechanisms are incompletely understood. Sphingolipids such as ceramide regulate lung injury, and their composition changes as a function of time in stored blood. Here, we tested the hypothesis that aged platelets may induce lung injury via a sphingolipid-mediated mechanism. To assess this hypothesis, a two-hit mouse model was devised. Recipient mice were treated with 2 mg/kg intraperitoneal lipopolysaccharide (priming) 2 h before transfusion of 10 ml/kg stored (1-5 days) platelets treated with or without addition of acid sphingomyelinase inhibitor ARC39 or platelets from acid sphingomyelinase-deficient mice, which both reduce ceramide formation. Transfused mice were examined for signs of pulmonary neutrophil accumulation, endothelial barrier dysfunction, and histological evidence of lung injury. Sphingolipid profiles in stored platelets were analyzed by mass spectrophotometry. Transfusion of aged platelets into primed mice induced characteristic features of lung injury, which increased in severity as a function of storage time. Ceramide accumulated in platelets during storage, but this was attenuated by ARC39 or in acid sphingomyelinase-deficient platelets. Compared with wild-type platelets, transfusion of ARC39-treated or acid sphingomyelinase-deficient aged platelets alleviated lung injury. Aged platelets elicit lung injury in primed recipient mice, which can be alleviated by pharmacological inhibition or genetic deletion of acid sphingomyelinase. Interventions targeting sphingolipid formation represent a promising strategy to increase the safety and longevity of stored blood products.
Background: Post-traumatic stress disorder (PTSD) is one of the more commonly occurring mental disorders following potentially traumatizing events soldiers may encounter when deployed abroad. One of the first-line recommended treatment options is eye movement desensitization and reprocessing (EMDR). The number of studies assessing the effectiveness of EMDR in German soldiers under routine conditions is currently almost nil. Methods: A retrospective, quasi-experimental effectiveness study on EMDR in an inpatient setting is presented using a prepost design. The study compares symptom reduction in soldiers (N = 78) with a wait-list (N = 18). Effect sizes of EMDR were measured for PTSD, symptoms of depression, and general mental health. Results: Effect size for EMDR treatment of PTSD was d = 0.77; 95% confidence interval (CI): 0.51 to 1.36, for symptoms of depression d = 0.99; 95% CI: 0.31 to 1.36, and for general psychiatric symptoms d = 0.53; 95% CI: 0.17 to 1.21. The effects resulting from EMDR treatment were somewhat weaker than those reported in comparable studies in civilians. Conclusion: EMDR therapy is an effective treatment to reduce symptoms of PTSD and depression. However, in the military context it needs to be complemented by treatment options that specifically address further conditions perpetuating the disorders.
Phylogeography of the Small Indian Civet and Origin of Introductions to Western Indian Ocean Islands
(2016)
The biogeographic dynamics affecting the Indian subcontinent, East and Southeast Asia during the Plio-Pleistocene has generated complex biodiversity patterns. We assessed the molecular biogeography of the small Indian civet (Viverricula indica) through mitogenome and cytochrome b + control region sequencing of 89 historical and modern samples to (1) establish a time-calibrated phylogeography across the species’ native range and (2) test introduction scenarios to western Indian Ocean islands. Bayesian phylogenetic analyses identified 3 geographic lineages (East Asia, sister-group to Southeast Asia and the Indian subcontinent + northern Indochina) diverging 3.2–2.3 million years ago (Mya), with no clear signature of past demographic expansion. Within Southeast Asia, Balinese populations separated from the rest 2.6–1.3 Mya. Western Indian Ocean populations were assigned to the Indian subcontinent + northern Indochina lineage and had the lowest mitochondrial diversity. Approximate Bayesian computation did not distinguish between single versus multiple introduction scenarios. The early diversification of the small Indian civet was likely shaped by humid periods in the Late Pliocene–Early Pleistocene that created evergreen rainforest barriers, generating areas of intra-specific endemism in the Indian subcontinent, East, and Southeast Asia. Later, Pleistocene dispersals through drier conditions in South and Southeast Asia were likely, giving rise to the species’ current natural distribution. Our molecular data supported the delineation of only 4 subspecies in V. indica, including an endemic Balinese lineage. Our study also highlighted the influence of prefirst millennium AD introductions to western Indian Ocean islands, with Indian and/or Arab traders probably introducing the species for its civet oil.
Job satisfaction has been found to impact behavioral choices at the workplace. Since levels of satisfaction are not guaranteed to remain high, understanding the consequences of job dissatisfaction is essential. Hence, I analyze the relationship between a worker’s job satisfaction and her training investments. Based on my theoretical model, I expect a U-shaped relationship if dissatisfied workers attempt to improve the situation or plan to quit. In contrast, there is an overall positive relationship if dissatisfied workers neglect their duties. Using logit regressions with the Household, Income and Labour Dynamics in Australia (HILDA) survey I find tentative evidence that there is on average an overall positive relationship with a 1 standard deviation increase in job satisfaction being associated with a 1.5% increased likelihood of participating in training. A closer inspection of the reasons for training as well as quit intentions reveals some hints of a U-shaped relationship. My results highlight the importance of considering the source of dissatisfaction as there are heterogeneous effects along different job satisfaction facets.
The Leopard cat Prionailurus bengalensis is a habitat generalist that is widely distributed across Southeast Asia. Based on morphological traits, this species has been subdivided into 12 subspecies. Thus far, there have been few molecular studies investigating intraspecific variation, and those had been limited in geographic scope. For this reason, we aimed to study the genetic structure and evolutionary history of this species across its very large distribution range in Asia. We employed both PCR-based (short mtDNA fragments, 94 samples) and high throughput sequencing based methods (whole mitochondrial genomes, 52 samples) on archival, noninvasively collected and fresh samples to investigate the distribution of intraspecific genetic variation. Our comprehensive sampling coupled with the improved resolution of a mitochondrial genome analyses provided strong support for a deep split between Mainland and Sundaic Leopard cats. Although we identified multiple haplogroups within the species’ distribution, we found no matrilineal evidence for the distinction of 12 subspecies. In the context of Leopard cat biogeography, we cautiously recommend a revision of the Prionailurus bengalensis subspecific taxonomy: namely, a reduction to 4 subspecies (2 mainland and 2 Sundaic forms).
We investigate the effect of the COVID-19 pandemic on self-employed people’s mental health. Using representative longitudinal survey data from Germany, we reveal differential effects by gender: whereas self-employed women experienced a substantial deterioration in their mental health, self-employed men displayed no significant changes up to early 2021. Financial losses are important in explaining these differences. In addition, we find larger mental health responses among self-employed women who were directly affected by government-imposed restrictions and bore an increased childcare burden due to school and daycare closures. We also find that self-employed individuals who are more resilient coped better with the crisis.
In light of climate change mitigation efforts, revenues from climate policies are growing, with no consensus yet on how they should be used. Potential efficiency gains from reducing distortionary taxes and the distributional implications of different revenue recycling schemes are currently debated. To account for households heterogeneity and dynamic trade-offs, we study the macroeconomic and welfare performance of different revenue recycling schemes using an Environmental Two-Agent New-Keynesian model, calibrated on the German economy. We find that, in the long run, welfare gains are higher when revenues are used to reduce distortionary taxes on capital, but this comes at the cost of higher inequality: while all households prefer labor income tax reductions to lump-sum transfers, only financially unconstrained households are better off when reducing taxes on capital income. Interestingly, we find that over the transition period relevant to meet short-medium run climate targets, labor income tax cuts are the most efficient and equitable instrument.
Twenty two species of ectoparasites (Family Nycteribiidae: Nycteribia (Listropoda) schmidlii schmidlii, Nycteribia (Nycteribia) latreillii, Nycteribia (Nycteribia) pedicularia, Penicillidia (Penicillidia) dufourii, and Phthiridium biarticulatum; Family Streblidae: Brachytarsina (Brachytarsina) flavipennis and Raymondia huberi; Order Siphonaptera: Rhinolophopsylla unipectinata arabs, Nycteridopsylla longiceps, Araeopsylla gestroi, Ischnopsyllus intermedius, and Ischnopsyllus octactenus; Order Heteroptera: Cimex pipistrelli, Cimex lectularius, and Cacodmus vicinus; Class Arachnida: Order Mesostigmata: Spinturnix myoti and Eyndhovenia euryalis; Order Ixodida: Family Argasidae: Argas transgariepinus and Argas vespertilionis; Family Ixodidae: Hyalomma dromedarii, Ixodes ricinus, and Ixodes vespertilionis) were recovered from 19 bat species in Algeria. New host records for bats are recorded for the first time: N. schmidlii from Rh. clivosus and R. cystops; N. latreillii from Rh. blasii and P. gaisleri; R. huberi from Rh. clivosus; C. pipistrelli from E. isabellinus and H. savii; C. vicinus from E. isabellinus; S. myoti from P. gaisleri; E. euryalis from P. gaisleri and Rh. blasii; A. vespertilionis from P. gaisleri; I. ricinus from T. teniotis and Rh. hipposideros and H. dromedarii from P. kuhlii. Raymondia huberi is recorded for the first time from Algeria.
Background: The purpose of this study was to analyze the prevalence of long-term benzodiazepine use in older adults treated in general and neuropsychiatric practices in Germany. Methods: This study included 32,182 patients over the age of 65 years who received benzodiazepine prescriptions for the first time between January 2010 and December 2014 in general and neuropsychiatric practices in Germany. Follow up lasted until July 2016. The main outcome measure was the proportion of patients treated with benzodiazepines for >6 months. Results: The proportion of patients with benzodiazepine therapy for >6 months increased with age (65-70 years: 12.3%; 71-80 years: 15.5%; 81-90 years: 23.7%; >90 years: 31.6%) but did not differ significantly between men (15.5%) and women (17.1%). The proportion of patients who received benzodiazepines for >6 months was higher among those with sleep disorders (21.1%), depression (20.8%) and dementia (32.1%) than among those with anxiety (15.5%). By contrast, this proportion was lower among people diagnosed with adjustment disorders (7.7%) and back pain (3.8%). Conclusion: Overall, long-term use of benzodiazepines is common in older people, particularly in patients over the age of 80 and in those diagnosed with dementia, sleep disorders, or depression.
Diabetic nephropathy is one of the most frequent, devastating and costly complications of diabetes. The available therapeutic approaches are limited. Dipeptidyl peptidase type 4 (DPP-4) inhibitors represent a new class of glucose-lowering drugs that might also have reno-protective properties. DPP-4 exists in two forms: a plasma membranebound form and a soluble form, and can exert many biological actions mainly through its peptidase activity and interaction with extracellular matrix components. The kidneys have the highest DPP-4 expression level in mammalians. DPP-4 expression and urinary activity are up-regulated in diabetic nephropathy, highlighting its role as a potential target to manage diabetic nephropathy. Preclinical animal studies and some clinical data suggest that DPP-4 inhibitors decrease the progression of diabetic nephropathy in a blood pressure-and glucose-independent manner. Many studies reported that these reno-protective effects could be due to increased half-life of DPP-4 substrates such as glucagon-like peptide-1 (GLP-1) and stromal derived factor-1 alpha (SDF-1a). However, the underlying mechanisms are far from being completely understood and clearly need further investigations.
A new isoflavone, 8-prenylmilldrone (1), and four new rotenoids, oblarotenoids A-D (2-5), along with nine known compounds (6-14), were isolated from the CH2Cl2/CH3OH (1:1) extract of the leaves of Millettia oblata ssp. teitensis by chromatographic separation. The purified compounds were identified by NMR spectroscopic and mass spectrometric analyses, whereas the absolute configurations of the rotenoids were established on the basis of chiroptical data and in some cases by single-crystal X-ray crystallography. Maximaisoflavone J (11) and oblarotenoid C (4) showed weak activity against the human breast cancer cell line MDA-MB-231 with IC50 values of 33.3 and 93.8 mu M, respectively.
Transient receptor potential channels (TRP channels) are cation selective transmembrane receptors with diverse structures, activation mechanisms and physiological functions. TRP channels act as cellular sensors for a plethora of stimuli, including temperature, membrane voltage, oxidative stress, mechanical stimuli, pH and endogenous as well as exogenous ligands, thereby illustrating their versatility. As such, TRP channels regulate various functions in both excitable and non-excitable cells, mainly by mediating Ca2+ homeostasis. Dysregulation of TRP channels is implicated in many pathologies, including cardiovascular diseases, muscular dystrophies and hyperalgesia. However, the importance of TRP channel expression, physiological function and regulation in chondrocytes and intervertebral disc (IVD) cells is largely unexplored. Osteoarthritis (OA) and degenerative disc disease (DDD) are chronic age-related disorders that significantly affect the quality of life by causing pain, activity limitation and disability. Furthermore, currently available therapies cannot effectively slow-down or stop progression of these diseases. Both OA and DDD are characterised by reduced tissue cellularity, enhanced inflammatory responses and molecular, structural and mechanical alterations of the extracellular matrix, hence affecting load distribution and reducing joint flexibility. However, knowledge on how chondrocytes and IVD cells sense their microenvironment and respond to its changes is still limited. In this review, we introduced six families of mammalian TRP channels, their mechanisms of activation as well as activation-driven cellular consequences. We summarised the current knowledge on TRP channel expression and activity in chondrocytes and IVD cells and the significance of TRP channels as therapeutic targets for the treatment of OA and DDD.
Clinical supervision is regarded as one of the most important components of psychotherapy training. In clinical practice, it has been found that the implementation of clinical supervision varies substantially and often differs from the recommendations made in the literature. The objective of the current study was to investigate the frequency of topics (e.g. ethical issues) and techniques (e.g. role play) in the clinical supervision of psychotherapy trainees in Germany. To this end, we considered supervisions in cognitive behavioural therapy (CBT) and psychodynamic therapy (PT). A total of 791 psychotherapy trainees (533 CBT and 242 PT) were asked via the internet to provide information about their current supervision sessions. We found that clinical supervision in psychotherapy training addressed topics that are central for the effective treatment of supervised patients (i.e. therapeutic interventions, therapeutic alliance, maintaining factors, and therapeutic goals). However, the most frequently used intervention in clinical supervision in psychotherapy training was case discussion. Rarely were techniques used that allowed the supervisor to give the supervisee feedback based on the supervisee's demonstrated competencies. For example, 46% of the supervisors never used audiotapes or videotapes in the supervision. Differences between CBT and PT were rather small. Current practice regarding the techniques used in clinical supervision for psychotherapy trainees contradicts recommendations for active and feedback-oriented clinical supervision. Thus the potential of clinical supervision might not be fully used in clinical practice.
We study the degree of second-order coherence of the emission of a high-power multi-quantum well superluminescent diode with a lateral tapered amplifier section with and without optical feedback. When operated in an external cavity, the degree of second-order coherence changed from the almost thermal case of g((2))(0)approximate to 1.9 towards the mostly coherent case of g((2)) (0) approximate to 1.2 when the injection current at the tapered section was increased. We found good agreement with semi-classical laser theory near and below threshold while above laser threshold a slightly higher g((2))(0) was observed. As a free running device, the superluminescent diode yielded more than 400 mW of optical output power with good spatial beam quality of M-slow(2) < 1.6. In this case, the degree of second-order coherence dropped only slightly from 1.9 at low powers to 1.6 at the maximum output power. To our knowledge, this is the first investigation of a high-power tapered superluminescent diode concerning the degree of second-order coherence. Such a device might be useful for real-world applications probing the second order coherence function, such as ghost imaging.
Paclitaxel is a commonly used cytotoxic anticancer drug with potentially life-threatening toxicity at therapeutic doses and high interindividual pharmacokinetic variability. Thus, drug and effect monitoring is indicated to control dose-limiting neutropenia. Joerger et al. (2016) developed a dose individualization algorithm based on a pharmacokinetic (PK)/pharmacodynamic (PD) model describing paclitaxel and neutrophil concentrations. Furthermore, the algorithm was prospectively compared in a clinical trial against standard dosing (Central European Society for Anticancer Drug Research Study of Paclitaxel Therapeutic Drug Monitoring; 365 patients, 720 cycles) but did not substantially improve neutropenia. This might be caused by misspecifications in the PK/PD model underlying the algorithm, especially without consideration of the observed cumulative pattern of neutropenia or the platinum-based combination therapy, both impacting neutropenia. This work aimed to externally evaluate the original PK/PD model for potential misspecifications and to refine the PK/PD model while considering the cumulative neutropenia pattern and the combination therapy. An underprediction was observed for the PK (658 samples), the PK parameters, and these parameters were re-estimated using the original estimates as prior information. Neutrophil concentrations (3274 samples) were over-predicted by the PK/PD model, especially for later treatment cycles when the cumulative pattern aggravated neutropenia. Three different modeling approaches (two from the literature and one newly developed) were investigated. The newly developed model, which implemented the bone marrow hypothesis semiphysiologically, was superior. This model further included an additive effect for toxicity of carboplatin combination therapy. Overall, a physiologically plausible PK/PD model was developed that can be used for dose adaptation simulations and prospective studies to further improve paclitaxel/ carboplatin combination therapy.
Der Leserbrief fokussiert in weiten Teilen auf das Gutachterwesen, weshalb wir ausschließlich auf die inhaltlichen Punkte im Zusammenhang mit unserer Arbeit eingehen. Untersucht wurden schmerzpsychologische Interventionen, wie beschrieben definiert als psychologische Interventionen, deren primäres Ziel die Schmerzreduktion war.
Die extrahierten Zielgrößen, wie Lebensqualität oder Depressivität, ergaben sich aus den in den Primärstudien untersuchten Hauptoutcomes und nicht aus der Suchstrategie.
Zur Einschätzung der methodischen Qualität der Primärstudien konnte ein Kriterium des von Johannsen und Kollegen [2] gebildeten Scores nicht berücksichtigt werden, da die eingeschlossenen Primärstudien keine metaanalytische Zusammenfassung erlaubten. Stellt man dies in Rechnung, bleibt die Vergleichbarkeit beider Werte erhalten.
Die Evidenzsynthese erfolgte narrativ in Text- und Tabellenform, d. h. in Form einer strukturierten Zusammenfassung und Diskussion von Studien [1].
Um unsere Arbeit zu fokussieren, hätten wir eine weitergehende Gegenüberstellung wie auch eine Überprüfung von Zitaten und Übersetzungen selbstverständlich vorgenommen, wenn wir den Hinweis dazu vor Publikation erhalten hätten.
The ecological relevance of fungi in freshwater ecosystems is becoming increasingly evident, particularly in processing the extensive amounts of polymeric organic carbon such as cellulose, chitin, and humic substances (HS). We isolated several fungal strains from oligo-mesotrophic Lake Stechlin, Brandenburg, Germany, and analyzed their ability to degrade polymeric-like substrates. Using liquid chromatography-organic carbon detection, we determined the byproducts of HS transformation by the freshwater fungus Cladosporium sp. KR14. We demonstrate the ability of this fungus to degrade and simultaneously synthesize HS, and that transformation processes were intensified when iron, as indicator of the occurrence of Fenton reactions, was present in the medium. Furthermore, we showed that structural complexity of the HS produced changed with the availability of other polymeric substances in the medium. Our study highlights the contribution of freshwater Ascomycetes to the transformation of complex organic compounds. As such, it has important implications for understanding the ecological contribution of fungi to aquatic food webs and related biogeochemical cycles.
Context. Massive stars severely influence their environment by their strong ionizing radiation and by the momentum and kinetic energy input provided by their stellar winds and supernovae. Quantitative analyses of massive stars are required to understand how their feedback creates and shapes large scale structures of the interstellar medium. The giant H II region N206 in the Large Magellanic Cloud contains an OB association that powers a superbubble filled with hot X-ray emitting gas, serving as an ideal laboratory in this context. Aims. We aim to estimate stellar and wind parameters of all OB stars in N206 by means of quantitative spectroscopic analyses. In this first paper, we focus on the nine Of-type stars located in this region. We determine their ionizing flux and wind mechanical energy. The analysis of nitrogen abundances in our sample probes rotational mixing. Methods. We obtained optical spectra with the multi-object spectrograph FLAMES at the ESO-VLT. When possible, the optical spectroscopy was complemented by UV spectra from the HST, IUE, and FUSE archives. Detailed spectral classifications are presented for our sample Of-type stars. For the quantitative spectroscopic analysis we used the Potsdam Wolf-Rayet model atmosphere code. We determined the physical parameters and nitrogen abundances of our sample stars by fitting synthetic spectra to the observations. Results. The stellar and wind parameters of nine Of-type stars, which are largely derived from spectral analysis are used to construct wind momentum luminosity relationship. We find that our sample follows a relation close to the theoretical prediction, assuming clumped winds. The most massive star in the N206 association is an Of supergiant that has a very high mass-loss rate. Two objects in our sample reveal composite spectra, showing that the Of primaries have companions of late O subtype. All stars in our sample have an evolutionary age of less than 4 million yr, with the O2-type star being the youngest. All these stars show a systematic discrepancy between evolutionary and spectroscopic masses. All stars in our sample are nitrogen enriched. Nitrogen enrichment shows a clear correlation with increasing projected rotational velocities. Conclusions. The mechanical energy input from the Of stars alone is comparable to the energy stored in the N206 superbubble as measured from the observed X-ray and H alpha emission.
Word recognition in sentence reading is influenced by information from both preview and context. Recently, semantic preview effect (SPE) was observed being modulated by the constraint of context, indicating that context might accelerate the processing of semantically related preview words. Besides, SPE was found to depend on preview time, which suggests that SPE may change with different processing stages of preview words. Therefore, it raises the question of whether preview time-dependent SPE would be modulated by contextual constraint. In this study, we not only investigated the impact of contextual constraint on SPE in Chinese reading but also examined its dependency on preview time. The preview word and the target word were identical, semantically related or unrelated to the target word. The results showed a significant three-way interaction: The SPE depended on contextual constraint and preview time. In separate analyses for low and high contextual constraint of target words, the SPE significantly decreased with an increase in preview duration when the target word was of low constraint in the sentence. The effect was numerically in the same direction but weaker and statistically nonsignificant when the target word was highly constrained in the sentence. The results indicate that word processing in sentences is a dynamic process of integrating information from both preview (bottom-up) and context (top-down).
The visual number world
(2018)
In the domain of language research, the simultaneous presentation of a visual scene and its auditory description (i.e., the visual world paradigm) has been used to reveal the timing of mental mechanisms. Here we apply this rationale to the domain of numerical cognition in order to explore the differences between fast and slow arithmetic performance, and to further study the role of spatial-numerical associations during mental arithmetic. We presented 30 healthy adults simultaneously with visual displays containing four numbers and with auditory addition and subtraction problems. Analysis of eye movements revealed that participants look spontaneously at the numbers they currently process (operands, solution). Faster performance was characterized by shorter latencies prior to fixating the relevant numbers and fewer revisits to the first operand while computing the solution. These signatures of superior task performance were more pronounced for addition and visual numbers arranged in ascending order, and for subtraction and numbers arranged in descending order (compared to the opposite pairings). Our results show that the visual number world-paradigm provides on-line access to the mind during mental arithmetic, is able to capture variability in arithmetic performance, and is sensitive to visual layout manipulations that are otherwise not reflected in response time measurements.