Long‐Term Mechanical Circulatory Support in Pediatric Patients

This retrospective study reviews our results regarding the long‐term support in pediatric patients using two ventricular assist systems between January 2008 and April 2014. We implanted the Berlin Heart EXCOR in 29 patients (median age 3.4 years [interquartile range (IQR) 0.2–16.5], median weight 13 kg [IQR 4.2–67.2]). Twenty‐two patients (75.8%) received a left ventricular assist device. Three patients (10.3%) had single‐ventricle physiology. One patient (3.4%) had mechanical mitral valve prosthesis. The HeartWare System was implanted in nine patients. The median age was 15.6 years (IQR 12.2–17.9), and the median weight was 54.9 kg (IQR 27.7–66). In the Berlin Heart group, the median support time was 65 days (IQR 4–619), with 3647 days of cardiac support. Nineteen patients (65.5%) were transplanted, six patients (20.7%) recovered, one patient (3.4%) is on support, and three patients (10.3%) died on support. Survival rate was 89.7%. Fourteen blood pumps had been exchanged. Four patients (13.8%) had local signs of infection, and three patients (10.3%) had neurological complications. In the HeartWare group, the median support time was 180 days (IQR 1–1124), with 2839 days of cardiac support. Four patients (44.4%) had local signs of infection, and three (33.3%) had neurological complications. Eight patients (88.9%) have been transplanted, and one patient (11.1%) died on support. Survival rate was 88.9%. Excellent survival is possible after long‐term mechanical circulatory support in patients with two‐ and single‐ventricle physiology with a low rate of adverse events.     

Rescuing prefrontal cAMP-CREB pathway reverses working memory deficits during withdrawal from prolonged alcohol exposure

Both human and animal studies indicate that alcohol withdrawal following chronic alcohol consumption (CAC) impairs many of the cognitive functions which rely on the prefrontal cortex (PFC). A candidate signaling cascade contributing to memory deficits during alcohol withdrawal is the protein kinase A (PKA)/cAMP-responsive element binding (CREB) cascade, although the role of PKA/CREB cascade in behavioral and molecular changes during sustained withdrawal period remains largely unknown. We demonstrated that 1 week (1W) or 6 weeks (6W) withdrawal after 6-month CAC impairs working memory (WM) in a T-maze spontaneous alternation task and reduces phosphorylated CREB (pCREB) in the PFC but not the dorsal CA1 region (dCA1) of the hippocampus compared with CAC and water conditions. In contrast, both CAC-unimpaired and withdrawn-impaired mice exhibited decreased pCREB in dCA1 as well as reduced histone H4 acetylation in PFC and dCA1, compared with water controls. Next, we showed that enhancing CREB activity through rolipram administration prior to testing improved WM performance in withdrawn mice but impaired WM function in water mice. In addition, WM improvement correlates positively with increased pCREB level selectively in the PFC of withdrawn mice. Results further indicate that direct infusion of the PKA activator (Sp-cAMPS) into the PFC significantly improves or impairs, respectively, WM performance in withdrawn and water animals. In contrast, Sp-cAMPS had no effect on WM when infused into the dCA1. Collectively, these results provide strong support that dysregulation of PKA/CREB-dependent processes in prefrontal neurons is a critical molecular signature underlying cognitive decline during alcohol withdrawal.     

Dynamic interplays between memory systems depend on practice: the hippocampus is not always the first to provide solution

Previous studies showed that the optimization of behavioral performance through extended training depends on a switch from hippocampus-based memory to striatum-based habit. Here we investigate whether the amount of training within one learning session influences the retention of memory for hippocampal versus striatal strategies. Mice were trained to search for a submerged cue-marked platform which remained in the same spatial location in the water-maze for each of three training regimens (4, 12 or 22 trials). Subsequently, they were either tested for retention of memory 1 h or 24 h later on a probe test or killed at different time points over a 7-h period to determine the kinetic of cAMP response element binding protein (CREB) phosphorylation in both memory systems. During the probe test mice had to choose between a submerged platform located in the same position as during the acquisition phase (spatial solution) and a platform marked by the cue but located in the opposite quadrant of the pool (cue-guided solution). Results showed that the animals first preferred the cue-marked platform, which represents a strategy that was selectively impaired by lesions of the dorsolateral caudate-putamen. With further practice, or context pre-exposure, animals transiently favored the hippocampus-dependent place solution but finally, both strategies became interchangeable and insensitive to either lesion. CREB phosphorylation increased in both memory systems following acquisition but training-dependent changes selectively occurred in the hippocampus wherein biphasic activation was initiated by the four-trial training and blocked by training for 22 trials. These findings indicate that learning in one session consists of three acquisition stages with parallel engagement of multiple memory systems at the beginning of learning. They suggest, however, that, in a later phase, dynamic interplays promote the use of the most adapted brain system depending on practice and this is accompanied by specific patterns of CREB phosphorylation in the hippocampus.     

Arzneimitteltherapiesicherheit im Krankenhaus

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Arzneimittelbezogene Probleme (ABP) sind eine signifikante und häufig vermeidbare Ursache für Morbidität und...     

Tabakprävention in Deutschland und international

In Germany, several tobacco control policies have been implemented since 2002. These include tobacco tax increases, restrictions on sale and advertising, smoke-free legislation, and health warnings on tobacco products. All of those contributed to the emerging trend towards nonsmoking – especially among youth and young adults – as well as to the impressive decline of cigarette sales from 145.1 billion cigarettes in 2002 to 75.8 billion in 2017. Despite this, still 13% of all deaths are attributable to smoking in Germany.Other countries are acting in a more committed manner and are implementing much stronger tobacco control policies than Germany. Germany is the only EU country that doesn’t yet have a billboard ban on tobacco advertising, the smoke-free legislation is weak due to exceptions, and for more than ten years the tobacco tax has not been markedly increased. Globally, more than 30 countries have implemented at the highest possible level four of the six most important tobacco control policies as defined by the World Health Organization – Germany has implemented only two policies. Therefore, on an international scale, Germany is clearly lagging behind in tobacco control and on the European Tobacco Control Scale it is ranked second last. A more committed and compelling approach towards tobacco control is required in Germany to reach a position in terms of protecting the population from the devastating health hazards of smoking, which would be appropriate for a leading industrial nation.     

Frühe intra- und postoperative Komplikationen der C1-C2-Fixation nach Goel-Harms

Die Unfallchirurgie - Densfrakturen zählen zu den häufigsten Verletzungen der Wirbelsäule. Neben den klassischen Verfahren kann die dorsale C1-C2-Fusion nach Goel-Harms als...     

Modulation of the Initial Mineralization Process of SaOS-2 Cells by Carbonic Anhydrase Activators and Polyphosphate

Ca-phosphate/hydroxyapatite (HA) crystals constitute the mineral matrix of vertebrate bones, while Ca-carbonate is the predominant mineral of many invertebrates, like mollusks. Recent results suggest that CaCO₃ is also synthesized during early bone formation. We demonstrate that carbonic anhydrase-driven CaCO₃ formation in vitro is activated by organic extracts from the demosponge Suberites domuncula as well as by quinolinic acid, one component isolated from these extracts. Further results revealed that the stimulatory effect of bicarbonate (HCO₃ ^?) ions on mineralization of osteoblast-like SaOS-2 cells is strongly enhanced if the cells are exposed to inorganic polyphosphate (polyP), a linear polymer of phosphate linked by energy-rich phosphodiester bonds. The effect of polyP, administered as polyP (Ca²⁺ salt), on HA formation was found to be amplified by addition of the carbonic anhydrase-activating sponge extract or quinolinic acid. Our results support the assumption that CaCO₃ deposits, acting as bio-seeds for Ca-carbonated phosphate formation, are formed as an intermediate during HA mineralization and that the carbonic anhydrase-mediated formation of those deposits is under a positive–negative feedback control by bone alkaline phosphatase-dependent polyP metabolism, offering new targets for therapy of bone diseases/defects.     

Human exposure to airborne aniline and formation of methemoglobin: a contribution to occupational exposure limits

Aniline is an important starting material in the manufacture of polyurethane-based plastic materials. Aniline-derived methemoglobinemia (Met-Hb) is well described in exposed workers although information on the dose–response association is limited. We used an experimental design to study the association between aniline in air with the formation of Met-Hb in blood and the elimination of aniline in urine. A 6-h exposure of 2 ppm aniline in 19 non-smoking volunteers resulted in a time-dependent increase in Met-Hb in blood and aniline in urine. The maximum Met-Hb level in blood (mean 1.21 ± 0.29 %, range 0.80–2.07 %) and aniline excretion in urine (mean 168.0 ± 51.8 µg/L, range 79.5–418.3 µg/L) were observed at the end of exposure, with both parameters rapidly decreasing after the end of exposure. After 24 h, the mean level of Met-Hb (0.65 ± 0.18 %) returned to the basal level observed prior to the exposure (0.72 ± 0.19 %); whereas, slightly elevated levels of aniline were still present in urine (means 17.0 ± 17.1 vs. 5.7 ± 3.8 µg/L). No differences between males and females as well as between slow and fast acetylators were found. The results obtained after 6-h exposure were also comparable to those observed in four non-smoking volunteers after 8-h exposure. Maximum levels of Met-Hb and aniline in urine were 1.57 % and 305.6 µg/L, respectively. Overall, our results contribute to the risk assessment of aniline and as a result, the protection of workers from aniline-derived adverse health effects at the workplace.