Numerical modeling of microplastic interaction with fine sediment under estuarine conditions.

Microplastic (MP) pollution is an important challenge for human life which has consequently affected the natural system of other organisms. Mismanagement and also careless handling of plastics in daily life has led to an accelerating contamination of air, water and soil compartments with MP. Under estuarine conditions, interactions with suspended particulate matter (SPM) like fine sediment in the water column play an important role on the fate of MP. Further studies to better understand the corresponding transport and accumulation mechanisms are required. This paper aims at providing a new modeling approach improving the MP settling velocity formulation based on higher suspended fine sediment concentrations, as i.e. existent in estuarine turbidity zones (ETZ). The capability of the suggested approach is examined through the modeling of released MP transport in water and their interactions with fine sediment (cohesive sediment/fluid mud). The model results suggest higher concentrations of MP in ETZ, both in the water column as well as the bed sediment, which is also supported by measurements. The key process in the modeling approach is the integration of small MP particles into estuarine fine sediment aggregates. This is realized by means of a threshold sediment concentration, above which the effective MP settling velocity increasingly approaches that of the sediment aggregates. The model results are in good agreement with measured MP mass concentrations. Moreover, the model results also show that lighter small MP particles can easier escape the ETZ towards the open sea.

Pulmonary hypertension and valvular heart disease.

Pulmonary hypertension (PH) is an important contributor to morbidity and mortality in patients with left-sided heart disease, including valvular heart disease. In this context, elevated left atrial pressure primarily leads to the development of post-capillary PH. Despite the fact that repair of left-sided valvular heart disease by surgical or interventional approaches will improve PH, recent studies have highlighted that PH (pre- or post-interventional) remains an important predictor of long-term outcome. Here, we review the current knowledge on PH in valvular heart disease taking into account new hemodynamic PH definitions, and the distinction between post- and pre-capillary components of PH. A specific focus is on the precise characterization of hemodynamics and cardiopulmonary interaction, and on potential strategies for the management of residual PH after mitral or aortic valve interventions. In addition, we highlight the clinical significance of tricuspid regurgitation, which may occur as a primary condition or as a consequence of PH and right heart dilatation (functional). In this context, proper patient selection for potential tricuspid valve interventions is crucial. Finally, the article highlights gaps in evidence, and points toward future perspectives.

[Certification : Pro: indispensable component of quality]. / Zertifizierungen : Pro: unabdingbarer Bestandteil von Qualität.

Certification is a critical component of quality assurance in medicine. From the certification of individual persons, through units and up to whole hospitals, certification stimulates testing and optimization of treatment processes, thereby improving the quality of care. Minimum case numbers needed to acquire a certificate are an important and objective attribute of quality. Advantages of certification include an improved treatment of patients, structured training of new employees and enhanced cost efficiency.

[Platelet inhibition in patients with coronary, cerebral and peripheral macroangiopathy : What, when and how long?] / Thrombozytenaggregationshemmer bei koronarer, zerebraler und peripherer Makroangiopathie : Was, wann, wie lange?

BACKGROUND: Inhibition of platelet aggregation can reduce the rate of vascular events in patients with coronary artery disease, carotid artery stenosis and symptomatic peripheral arterial disease. The choice of platelet inhibitors in monotherapy and combination therapy as well as the duration of dual platelet inhibition depend on the clinical situation and individual patient characteristics. GOAL: The present review summarizes the latest data from clinical trials and recommendations regarding platelet inhibition in coronary, cerebral and peripheral arterial disease. DATA: A large number of randomized trials on platelet inhibition in different clinical situations have been performed, allowing evidence-based recommendations on the choice of drugs and duration of treatment. Moreover, new guidelines of European professional societies on platelet inhibition in patients with coronary, cerebral and peripheral arterial disease have been recently published. CONCLUSION: Based on latest randomized trials and major society guidelines, a number of recommendations on platelet inhibition in stable coronary artery disease, after stent implantation, after acute coronary syndromes and in cerebral and peripheral arterial disease can be made.

[Baroreceptor activation therapy for therapy-resistant hypertension: indications and patient selection : Recommendations of the BAT consensus group 2017]. / Barorezeptorakivierungstherapie bei therapierefraktärer Hypertonie: Indikation und Patientenselektion : Empfehlungen der BAT-Konsensusgruppe 2017.

Baroreceptor activation therapy (BAT) has been available for several years for treatment of therapy-refractory hypertension (trHTN). This procedure is currently being carried out in a limited number of centers in Germany, also with the aim of offering a high level of expertise through sufficient experience; however, a growing number of patients who are treated with BAT experience problems that treating physicians are confronted with in routine medical practice. In order to address these problems, a consensus conference was held with experts in the field of trHTN in November 2016, which summarizes the current evidence and experience as well as the problem areas in handling BAT patients.

[Baroreflex activation therapy. A novel interventional approach to treat heart failure with reduced ejection fraction]. / Baroreflexaktivierungstherapie. Ein neuer interventioneller Ansatz zur Behandlung der systolischen Herzinsuffizienz.

Sympathovagal imbalance plays an important role in the progression of heart failure with reduced ejection fraction. Baroreflex activation therapy (BAT), i. e. electrical stimulation of baroreceptors located at the carotid sinus, can reduce sympathetic and enhance parasympathetic tone. Large animal studies on BAT demonstrated improvements in cardiac function, arrhythmogenic risk and a survival benefit compared to untreated controls. The recently published Neo Randomized Heart Failure Study, the first multicenter, randomized and controlled trial of optimal medical and device therapy alone or plus BAT in patients with a left ventricular ejection fraction ≤ 35 %, demonstrated a reasonable safety profile of BAT in this severely ill patient population and no relevant interactions with other devices. The study found significant improvements in the New York Heart Association (NYHA) class of heart failure, quality of life as well as 6 min walking distance and data pointed to a reduction in hospitalization rates. Moreover, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were significantly reduced. This review gives an overview on BAT for the treatment of heart failure with reduced ejection fraction, from the rationale and animal experiments to the most recent clinical data and future perspectives.

Genetic ablation of ataxin-2 increases several global translation factors in their transcript abundance but decreases translation rate.

Spinocerebellar ataxia type 2 (SCA2) and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders, caused or modified by an unstable CAG-repeat expansion in the SCA2 gene, which encodes a polyglutamine (polyQ) domain expansion in ataxin-2 (ATXN2). ATXN2 is an RNA-binding protein and interacts with the poly(A)-binding protein PABPC1, localizing to ribosomes at the rough endoplasmic reticulum. Under cell stress, ATXN2, PABPC1 and small ribosomal subunits are relocated to stress granules, where mRNAs are protected from translation and from degradation. It is unknown whether ATXN2 associates preferentially with specific mRNAs or how it modulates RNA processing. Here, we investigated the RNA profile of the liver and cerebellum from Atxn2 knockout (Atxn2 (-/-)) mice at two adult ages, employing oligonucleotide microarrays. Prominent increases were observed for Lsm12/Paip1 (>2-fold), translation modulators known as protein interactor/competitor of ATXN2 and for Plin3/Mttp (>1.3-fold), known as apolipoprotein modulators in agreement with the hepatosteatosis phenotype of the Atxn2 (-/-) mice. Consistent modest upregulations were also observed for many factors in the ribosome and the translation/secretion apparatus. Quantitative reverse transcriptase PCR in liver tissue validated >1.2-fold upregulations for the ribosomal biogenesis modulator Nop10, the ribosomal components Rps10, Rps18, Rpl14, Rpl18, Gnb2l1, the translation initiation factors Eif2s2, Eif3s6, Eif4b, Pabpc1 and the rER translocase factors Srp14, Ssr1, Sec61b. Quantitative immunoblots substantiated the increased abundance of NOP10, RPS3, RPS6, RPS10, RPS18, GNB2L1 in SDS protein fractions, and of PABPC1. In mouse embryonal fibroblasts, ATXN2 absence also enhanced phosphorylation of the ribosomal protein S6 during growth stimulation, while impairing the rate of overall protein synthesis rates, suggesting a block between the enhanced translation drive and the impaired execution. Thus, the physiological role of ATXN2 subtly modifies the abundance of cellular translation factors as well as global translation.

Development of electrical activity in cardiac myocyte aggregates derived from mouse embryonic stem cells.

Embryonic stem cells differentiate into cardiac myocytes, repeating in vitro the structural and molecular changes associated with cardiac development. Currently, it is not clear whether the electrophysiological properties of the multicellular cardiac structure follow cardiac maturation as well. In long-term recordings of extracellular field potentials with microelectrode arrays consisting of 60 substrate-integrated electrodes, we examined the electrophysiological properties during the ongoing differentiation process. The beating frequency of the growing preparations increased from 1 to 5 Hz concomitant to a decrease of the action potential duration and action potential rise time. A developmental increase of the conduction velocity could be attributed to an increased expression of connexin43 gap junction channels. Whereas isoprenalin elicited a positive chronotropic response from the first day of spontaneous beating onward, a concentration-dependent negative chronotropic effect of carbachol only developed after approximately 4 days. The in vitro development of the three-dimensional cardiac preparation thus closely follows the development described for the mouse embryonic heart, making it an ideal model to monitor the differentiation of electrical activity in embryonic cardiomyocytes.

Nasopharyngeally and vertex recorded P300's in normal subjects.

The P300 waveform has been associated with cognitive activity during information processing, and the hippocampus has been discussed as a possible generator of this waveform. This being the case some would argue that it should be possible to record the P300 with a shorter latency and greater amplitude from an electrode placed as near the hippocampus as possible. Under local anaesthesia we inserted a specially constructed needle electrode through the left nostril in the recessus pharyngeus close to the hippocampus. The results did not support the hippocampal hypothesis. Nasopharyngeally recorded P300's were found to have significantly decreased amplitudes and extended latencies when compared to vertex recordings.

Abnormal glucocorticoid dependent increase of spiperone binding sites on lymphocytes from schizophrenics in vitro.

The attempt was made to revise experimentally the concept of spiperone binding to human peripheral lymphocytes as a peripheral marker for schizophrenic disorder. Although it was not possible to detect differences in spiperone binding in freshly isolated lymphocytes from schizophrenics and controls, a significant increase in spiperone binding became apparent when the lymphocytes from patients were cultured in vitro in the presence of physiological concentrations of glucocorticoids. From our findings we have to assume that glucocorticoid-dependent regulation of the gene(s) containing the coding for spiperone binding sites could be functionally affected in distinct forms of schizophrenic psychosis. The glucocorticoid-induced increase of spiperone binding of human lymphocytes could represent a dynamic peripheral marker system. It further has to be investigated whether this concept of a regulatory dysfunction, as observed in lymphocytes from schizophrenic patients, can be applied to the CNS in general.

Neuromuscular, autonomic and central cholinergic hyperactivity associated with thymoma and acetylcholine receptor-binding antibody.

Two cases of a neuromuscular hyperactivity syndrome associated with a proliferative thymoma and high serum titres of acetylcholine receptor (AChR) antibody with no signs of myasthenia are reported. The clinical and electrodiagnostic findings indicated generalized cholinergic hyperactivity at the neuromuscular junction and in the autonomic and central nervous system, resulting in generalized myokymia, excessive sweating and intermittent psychotic behaviour. The association with thymoma and raised AChR antibody suggests that this syndrome represents a unique type of autoimmune disease, in which antibodies against the AChR facilitate rather than inhibit cholinergic action. This conclusion is supported by the remission of symptoms after thymectomy and with immunosuppressive therapy in one case.

Impairment of hormone dependent signal transfer by chronic SSPE virus infection.

In a CNS-derived cell line, the cellular response to hormonal stimulation, represented by the rise of intracellular cAMP levels, is impaired under the influence of a persisting neurotropic virus infection. This dysfunction is caused by the decrease in adenylate cyclase activity, most probably due to the virus-induced loss of active catalytic units.

Rabies virus infection selectively impairs membrane receptor functions in neuronal model cells.

A persistent infection with rabies virus (HEP-Flury) was established in the CNS-derived hybrid cell line 108CC15 which possesses specific membrane receptors for prostaglandins, catecholamines and acetylcholine. We report a differential virus influence on the specific receptor response to PGE, isoproterenol and acetycholine as indicated by typical changes of the intracellular cyclic AMP levels. As the adenylate cyclase activity was unchanged in infected cells in vitro, a selective virus influence on specific receptors themselves or their coupling to the cAMP synthesizing system must be considered.