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1.
Die Anaesthesiologie - Der Mangel an automatischen externen Defibrillatoren (AED) und die fehlende Kenntnis von Ersthelfern im Umgang mit diesen Geräten haben in Deutschland zu einer...  相似文献   
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MALT1 is a key mediator of NF-κB signaling and a main driver of B-cell lymphomas. Remarkably, MALT1 is expressed in the majority of pancreatic ductal adenocarcinomas (PDACs) as well, but absent from normal exocrine pancreatic tissue. Following, MALT1 shows off to be a specific target in cancer cells of PDAC without affecting regular pancreatic cells. Therefore, we studied the impact of pharmacological MALT1 inhibition in pancreatic cancer and showed promising effects on tumor progression. Mepazine (Mep), a phenothiazine derivative, is a known potent MALT1 inhibitor. Newly, we described that biperiden (Bip) is a potent MALT1 inhibitor with even less pharmacological side effects. Thus, Bip is a promising drug leading to reduced proliferation and increased apoptosis in PDAC cells in vitro and in vivo. By compromising MALT1 activity, nuclear translocation of c-Rel is prevented. c-Rel is critical for NF-κB-dependent inhibition of apoptosis. Hence, off-label use of Bip or Mep represents a promising new therapeutic approach to PDAC treatment. Regularly, the Anticholinergicum Bip is used to treat neurological side effects of Phenothiazines, like extrapyramidal symptoms.  相似文献   
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Lately, experts have turned to historical evidence to uncover the default mode of our sleep pattern. Even though there are some notable exceptions, most historians use a qualitative methodology based on scattered evidence in diaries, letters, novels, medical treatise and other literary sources. To provide fresh perspective in the debate, the present article develops a more quantitative approach. Drawing fresh evidence from early modern criminal records – viz the eyewitness reports of the Hoge Vierschaer or the local criminal court in Antwerp – we are able to debunk some classic stereotypes about premodern sleep patterns. Data reveal that most 18th‐century Antwerpers slept fewer hours than we would expect, slumbered in a monophasic way and rarely if ever took a nap during the day. Moreover, the start and end of sleep were less attuned to the solar cycle than we would imagine. Last but not least, the pattern also shows some fascinating weekly and seasonal variations.  相似文献   
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Sport Sciences for Health - Research pertaining to the superiority of athletes’ visio-spatial expertise when compared to non-athletes is conflicting. This discrepancy may arise due to a...  相似文献   
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The specific function of human skin-resident dendritic cell (DC) subsets in the regulation of immunity or tolerance is still a matter of debate. Langerhans cells (LC) induce anti-viral immune responses but, conversely to dermal DC, maintain tolerance to bacteria. However, the definite function of epidermal LC and cutaneous DC appears even more complex under inflammatory conditions. Here we investigated the immune responses of human immature monocyte-derived DC (MoDC) and LC-like cells (MoLC) upon stimulation with different Toll-like receptor ligands in the presence or absence of pro-inflammatory cytokines tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). In MoDC, bacterial antigens selectively up-regulated CD83 and CD86 expression and induced the release of T helper type 1 (Th1) and Th17 cytokines and led to a higher CCR7-dependent migratory capacity compared with a low responsiveness of MoLC. Importantly, MoLC activation with lipopolysaccharide under inflammatory conditions strongly enhanced a phenotypically mature state, increased IL-12p70, IL-23 and IL-6 production and Th1 cytokine secretion by CD4+ T cells. Treatment with poly(I:C) specifically up-regulated surface expression of co-stimulatory molecules and increased release of IL-12p70 in MoLC and co-stimulation with TNF-α and IL-1β further elevated Th1 and Th17 cytokine production. Poly(I:C)-induced up-regulation of type I interferon mRNA levels in MoLC and MoDC was Toll-like receptor 3-dependent but not, or only weakly, modulated by pro-inflammatory cytokines. Our results indicate that inflammatory conditions greatly facilitate recognition of bacteria by MoLC. Furthermore, we suggest a critical involvement of both subsets in innate defence against viruses, whereas inflammatory skin environments additionally favour MoLC as potent inducers of Th1 and Th17 cytokines.  相似文献   
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We report three families with arterial aneurysms and dissections in which variants predicted to be pathogenic were identified in SMAD2. Moreover, one variant occurred de novo in a proband with unaffected parents. SMAD2 is a strong candidate gene for arterial aneurysms and dissections given its role in the TGF‐β signaling pathway. Furthermore, although SMAD2 and SMAD3 probably have functionally distinct roles in cell signaling, they are structurally very similar. Our findings indicate that SMAD2 mutations are associated with arterial aneurysms and dissections and are in accordance with the observation that patients with pathogenic variants in genes encoding proteins involved in the TGF‐β signaling pathway exhibit arterial aneurysms and dissections as key features  相似文献   
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