Men and women are equal, but parliaments are dominated by men. In Europe, there has been a debate since the 1990s how to change this and promote gender parity in parliamentary representation. This ...contribution presents the approaches taken and discussed in Germany and France, and the considerable constitutional obstacles on the way to achieving this goal.
Aristophanes’ Frogs, first performed in 405 BCE, is an important milestone in Greek cultural history. The play is evidence of the beginnings of the establishment of a literary canon in Athens. The ...paper shows that the deaths of Euripides and Sophocles, in combination with the emergence of a reading culture, marked a break in the ways in which tragedy was perceived in Athens. It makes use of Jan Assmann’s concept of a transition from ritual to textual continuity to explore this capital step in the process of the canonization of ‘classical’ tragedy that would arrive at its fulfilment in the course of the fourth century BCE.
Newborn infants face a rapid surge of oxygen and a more protracted rise of unconjugated bilirubin after birth. Bilirubin has a strong antioxidant capacity by scavenging free radicals, but it also ...exerts direct toxicity. This study investigates whether cultured rat alveolar epithelial cells type II (AEC II) react differently to bilirubin under different oxygen concentrations. The toxic threshold concentration of bilirubin was narrowed down by means of a cell viability test. Subsequent analyses of bilirubin effects under 5% oxygen and 80% oxygen compared to 21% oxygen, as well as pretreatment with bilirubin after 4 h and 24 h of incubation, were performed to determine the induction of apoptosis and the gene expression of associated transcripts of cell death, proliferation, and redox-sensitive transcription factors. Oxidative stress led to an increased rate of cell death and induced transcripts of redox-sensitive signaling pathways. At a non-cytotoxic concentration of 400 nm, bilirubin attenuated oxidative stress-induced responses and possibly mediated cellular antioxidant defense by influencing Nrf2/Hif1α- and NFκB-mediated signaling pathways. In conclusion, the study demonstrates that rat AEC II cells are protected from oxidative stress-induced impairment by low-dose bilirubin.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In Germany, as in most modern democracies, the funding of political parties is a sensitive issue and even after a changeful history of party funding with many scandals the present model is not ...perfect. There is a combination of private funding and partial public funding (which must, however, not affect the freedom of the political parties from state influence Staatsfreiheit der Parteien), flanked by strict rules of financial accountability. Donations are the most controversial element. There is neither a ban on donations from companies nor an absolute limit for donations. Only donations of more than 50 000 € must be reported immediately and will be made public in a timely manner so that it is ensured that the citizens are informed about them before the next elections. Concerning public funding, there is an indirect funding through income tax reductions on membership fees and (limited) on donations, plus a direct public funding (per vote and per contribution), which must not be higher than the revenue from private funding. Since 2017, parties seeking to undermine or abolish the free and democratic constitutional order shall be excluded from the public funding. In order to ensure transparency, every party must submit for each calender year a correct and exhaustive audited public statement of accounts. In case of illegal donations or incorrectness of the statement there are sanctions, which are, however, rather soft. The Council of Europe’s Group of States against Corruption (GRECO) has criticised the intransparency arising from the fact that party donations up to 50 000 € do not need to be reported immediately but only in the annual statement of accounts, which may be published several months after the elections influenced by them. So there is still room for improvement.
Paracetamol is commonly used to treat fever and pain in pregnant women, but there are growing concerns that this may cause attention deficit hyperactivity disorder and autism spectrum disorder in the ...offspring. A growing number of epidemiological studies suggests that relative risks for these disorders increase by an average of about 25% following intrauterine paracetamol exposure. The data analyzed point to a dose-effect relationship but cannot fully account for unmeasured confounders, notably indication and genetic transmission. Only few experimental investigations have addressed this issue. Altered behavior has been demonstrated in offspring of paracetamol-gavaged pregnant rats, and paracetamol given at or prior to day 10 of life to newborn mice resulted in altered locomotor activity in response to a novel home environment in adulthood and blunted the analgesic effect of paracetamol given to adult animals. The molecular mechanisms that might mediate these effects are unknown. Paracetamol has diverse pharmacologic actions. It reduces prostaglandin formation via competitive inhibition of the peroxidase moiety of prostaglandin H2 synthase, while its metabolite
-arachidonoyl-phenolamine activates transient vanilloid-subtype 1 receptors and interferes with cannabinoid receptor signaling. The metabolite
-acetyl-p-benzo-quinone-imine, which is pivotal for liver damage after overdosing, exerts oxidative stress and depletes glutathione in the brain already at dosages below the hepatic toxicity threshold. Given the widespread use of paracetamol during pregnancy and the lack of safe alternatives, its impact on the developing brain deserves further investigation.
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While additional oxygen supply is often required for the survival of very premature infants in intensive care, this also brings an increasing risk of progressive lung diseases and poor long-term lung ...outcomes. Caffeine is administered to neonates in neonatal intensive care for the prevention and treatment of apneas and has been shown to reduce BPD incidence and the need for mechanical ventilation, although it is still unclear whether this is due to a direct pulmonary action via antagonism of adenosine receptors and/or an indirect action. This experimental study aims to investigate the action of caffeine on the oxidative stress response in pulmonary tissue in a hyperoxia-based model of bronchopulmonary dysplasia in newborn rats.
Newborn Wistar rats were exposed to 21% or 80% oxygen for 3 (P3) or 5 (P5) postnatal days with or without recovery on room air until postnatal day 15 (P15) and treated with vehicle or caffeine (10 mg/kg) every 48 h beginning on the day of birth. The lung tissue of the rat pups was examined for oxidative stress response at P3 and P5 immediately after oxygen exposure or after recovery in ambient air (P15) by immunohistological staining and analysis of lung homogenates by ELISA and qPCR.
Lungs of newborn rats, corresponding to the saccular stage of lung development and to the human lung developmental stage of preterms, showed increased rates of total glutathione and hydrogen peroxide, oxidative damage to DNA and lipids, and induction of second-phase mediators of antioxidative stress response (superoxide dismutase, heme oxygenase-1, and the Nrf2/Keap1 system) in response to hyperoxia. Caffeine reduced oxidative DNA damage and had a protective interference with the oxidative stress response.
In addition to the pharmacological antagonism of adenosine receptors, caffeine appears to be a potent antioxidant and modulates the hyperoxia-induced pulmonary oxidative stress response and thus protective properties in the BPD-associated animal model. Free-radical-induced damage caused by oxidative stress seems to be a biological mechanism progress of newborn diseases. New aspects of antioxidative therapeutic strategies to passivate oxidative stress-related injury should be in focus of further investigations.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Extracorporeal membrane oxygenation (ECMO) became an accepted therapy for the treatment of severe acute respiratory distress syndrome and chronic obstructive pulmonary disease. However, ...ECMO systems are still prone to thrombus formation and decrease of gas exchange over time. Therefore, it is necessary to conduct qualified studies to identify parameters for optimization of ECMO systems, and especially the oxygenator. However, commercially marketed oxygenators are not always appropriate and available for certain research use cases. Therefore, we aimed to design an oxygenator, which is suitable for various test conditions such as blood tests, numerical simulation, and membrane studies, and can be modified in membrane area size and manufactured in laboratory.
Methods
Main design criteria are a homogeneous blood flow without stagnation zones, low pressure drop, manufacturability in the lab, size variability with one set of housing parts and cost‐efficiency. Our newly designed oxygenator was tested comparatively regarding blood cell damage, gas transfer performance and pressure drop to prove the validity of the design in accordance with a commercial device.
Results
No statistically significant difference between the tested oxygenators was detected and our new oxygenator demonstrated sufficient hemocompatibility. Furthermore, our variable oxygenator has proven that it can be easily manufactured in the laboratory, allows to use various membrane fiber configurations and can be reopened easily and non‐destructively for analysis after use, and the original geometry is available for numerical simulations.
Conclusion
Therefore, we consider this newly developed device as a valuable tool for basic experimental and numerical research on the optimization of oxygenators.
Development and evaluation of a variable oxygenator.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Left atrial appendage (LAA) occlusion with WATCHMAN has emerged as viable alternative to vitamin K antagonists in randomized controlled trials.
EWOLUTION was designed to provide data in routine ...practice from a prospective multicenter registry.
A total of 1025 patients scheduled for a WATCHMAN implant were prospectively and sequentially enrolled at 47 centers. Indication for LAA closure was based on European Society of Cardiology guidelines. Follow-up and transesophageal echocardiography (TEE) were performed per local practice.
The baseline CHA
DS
-VASc score was 4.5 ± 1.6; the mean age was 73.4 ± 9 years; previous transient ischemic attack/ischemic stroke was present in 312 (30.5%), 155 (15.1%) had previous hemorrhagic stroke, and 320 (31.3%) had a history of major bleeding; and 750 (73%) were deemed unsuitable for oral anticoagulation therapy. WATCHMAN implant succeeded in 1005 (98.5%) of patients, without leaks >5 mm in 1002 (99.7%) with at least 1 TEE follow-up in 875 patients (87%). Antiplatelet therapy was used in 784 (83%), while vitamin K antagonists were used in only 75 (8%). At 1 year, mortality was 98 (9.8%), reflecting the advanced age and comorbidities in this population. Device thrombus was observed in 28 patients at routine TEE (3.7%) and was not correlated with the drug regimen (P = .14). Ischemic stroke rate was 1.1% (relative risk 84% vs estimated historical data); the major bleeding rate was 2.6% and was predominantly (2.3%) nonprocedure/device related.
LAA closure with the WATCHMAN device has a high implant and sealing success. This method of stroke risk reduction appears to be safe and effective with an ischemic stroke rate as low as 1.1%, even though 73% of patients had a contraindication to and were not using oral anticoagulation.
Background
In the total artificial heart (TAH), the inputs to the physiological control unit, preload, and afterload, are detected from intrinsic pump parameters (e.g., motor current). Within this ...study, their detection techniques are developed, and their reliability in pre‐ and afterload prediction is mapped for a broad range of cardiovascular system states.
Methods
We used ReinHeart TAH which is a fully implantable TAH with a plunger coil drive that is alternately emptying the left and right chambers. From the coil currents we first derived a force generated by the piston with respect to its position and then analyzed its pattern to detect (1) preload—chamber filling, found as piston position at begin ejection and (2) afterload—mean outflow pressures, determined as linearly calibrated average piston force during ejection. TAH is then integrated into a mock loop circulation (MLC) which is set to 135 different steady operating points varying in chamber filling (0%–100%, five steps), mean outflow pressures (system circulation: 60–90–120 mm Hg, pulmonary circulation: 15–30‐45 mm Hg), and heart cycle duration (171–600 ms in seven non‐equidistant steps). The detected preload and afterload are compared to MLC set values, and the errors are mapped.
Results
Respectively for the left and right chambers, the preload was detectable in 134 and 118 operating points and the mean error was ±3% and ±2%. The afterload was detectable in 135 and 87 operating points and the mean error was 37% and 30% respectively for left and right circulation. The operational points that are further away from homeostatic equilibrium values generally yielded larger errors. The largest errors were observed for right circulation at long cycle duration, low afterload, and low filling.
Conclusions
The study yields reliable preload estimation in a broad range of physiological states, particularly for left circulation. Detection of afterload needs further improvements. The study revealed a need for piston movement optimization within the ReinHeart TAH during the early phase of systole.
The intrinsic parameter (piston force) in total artificial heart (TAH) is studied to detect the preload and afterload as a ramp in the force profile curve and as a mean value during ejection, respectively. The TAH is integrated into a mock cardiovascular loop set to 135 different operational points varying in preload, afterload, and systole duration. The maps of detection errors reveal lower errors in detected preload, generally in the systemic circulation, at shorter systole duration, and in the vicinity of physiological preload and afterload values.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Schizophrenia is a chronic and debilitating mental illness characterized by a broad range of abnormal behaviors, including delusions and hallucinations, impaired cognitive function, as well as mood ...disturbances and social withdrawal. Due to the heterogeneous nature of the disease, the causes of schizophrenia are very complex; its etiology is believed to involve multiple brain regions and the connections between them, and includes alterations in both gray and white matter regions. The onset of symptoms varies with age and severity, and there is some debate over a degenerative or developmental etiology. Longitudinal magnetic resonance imaging studies have detected progressive gray matter loss in the first years of disease, suggesting neurodegeneration; but there is also increasing recognition of a temporal association between clinical complications at birth and disease onset that supports a neurodevelopmental origin. Presently, neuronal abnormalities in schizophrenia are better understood than alterations in myelin-producing cells of the brain, the oligodendrocytes, which are the predominant constituents of white matter structures. Proper white matter development and its structural integrity critically impacts brain connectivity, which affects sensorimotor coordination and cognitive ability. Evidence of defective white matter growth and compromised white matter integrity has been found in individuals at high risk of psychosis, and decreased numbers of mature oligodendrocytes are detected in schizophrenia patients. Inflammatory markers, including proinflammatory cytokines and chemokines, are also associated with psychosis. A relationship between risk of psychosis, white matter defects and prenatal inflammation is being established. Animal models of perinatal brain injury are successful in producing white matter damage in the brain, typified by hypomyelination and/or dysmyelination, impaired motor coordination and prepulse inhibition of the acoustic startle reflex, recapitulating structural and functional characteristics observed in schizophrenia. In addition, elevated expression of inflammation-related genes in brain tissue and increased production of cytokines by blood cells from patients with schizophrenia indicate immunological dysfunction and abnormal inflammatory responses, which are also important underlying features in experimental models. Microglia, resident immune defenders of the central nervous system, play important roles in the development and protection of neural cells, but can contribute to injury under pathological conditions. This article discusses oligodendroglial changes in schizophrenia and focuses on microglial activity in the context of the disease, in neonatal brain injury and in various experimental models of white matter damage. These include disorders associated with premature birth, and animal models of perinatal bacterial and viral infection, oxygen deprivation (hypoxia) and excess (hyperoxia), and elevated systemic proinflammatory cytokine levels. We briefly review the effects of treatment with antipsychotic and anti-inflammatory agents in models of perinatal brain injury, and comment on the therapeutic potential of these strategies. By understanding the neurobiological basis of oligodendroglial abnormalities in schizophrenia, it is hoped that patients will benefit from the availability of targeted and more efficacious treatment options.
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