We present the first examples of carbodiphosphorane (CDP) complexes with alkali metal cations (Li+ and Na+). The homoleptic CDPR stabilized Li and Na cations, respectively, were isolated as ...tris(silylamido) ferrates in the solid state. In solution, a chemical exchange process in the Li+ and Na+ complexes are at hand.
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•First examples of carbodiphosphorane (CDP) complexes with alkali metal cations (Li+ and Na+) were synthesised.•Coordination sphere of the cationic group 1 center is provided by two CDP ligands.•Li+ and Na+ complexes are in equilibrium with the starting materials in solution (chemical exchange process).
Reactions of carbodiphosphorane (CDPR) ligands with equimolar quantities of group 1 and Fe(II) bis(trimethylsilyl)amides result in the isolation of discrete CDP-stabilized ion pairs, M(CDPR)2+Fe{N(SiMe3)2}3− (M = Li, Na; R = hexaphenyl, cyclopropyl-tetraphenyl). X-ray diffraction analysis revealed that the coordination sphere of the cationic group 1 center is provided by two CDPR ligands. In the solid state, we investigated the influence of the ligand substituents on the resulting architecture of the title complexes by utilizing different CDP ligands. In solution, we examined the stability of these complexes by variable temperature NMR spectroscopy. This study revealed that all title complexes show lability in solution due to dynamic processes: they are subject to a chemical exchange with the corresponding starting materials.
Abstract Background In children older than 1 year with localised unresectable neuroblastoma (NB), treatment strategies are heterogeneous according to the national groups. The objective of this phase ...III non-randomised study was to evaluate the efficacy of conventional chemotherapy followed by surgery. Patients and methods In the presence of surgical risk factors (SRF), six courses of chemotherapy alternating Carboplatin–Etoposide and Vincristin–Cyclophosphamide–Doxorubicin were given, and surgical resection was attempted after four. Survival analyses were performed using an intention-to-treat approach. The main objective was to achieve a 5-year survival over 80%. Results Out of 191 registered children, 160 were evaluable. There were 62.5% older than 18 months and 52.5% had unfavourable histology according to International Neuroblastoma Pathology Classification (INPC). Chemotherapy reduced the number of SRFs by one third. Delayed surgery was attempted in 86.3% of patients and was complete or nearly complete in 74%. The 5-year EFS and OS were 76.4% and 87.6% respectively, with significant better results for patients younger than 18 months or with favourable histology. Conclusion This strategy provides encouraging results in children older than 1 year or 12 months with localised unresectable NB without MYCN amplification. However, in children older than 18 months and with unfavourable histology, additional treatment is recommended.
In neuroblastoma (NB), the presence of segmental chromosome alterations (SCAs) is associated with a higher risk of relapse.
In order to analyse the role of SCAs in infants with localised ...unresectable/disseminated NB without MYCN amplification, we have performed an array CGH analysis of tumours from infants enrolled in the prospective European INES trials.
Tumour samples from 218 out of 300 enroled patients could be analysed. Segmental chromosome alterations were observed in 11%, 20% and 59% of infants enroled in trials INES99.1 (localised unresectable NB), INES99.2 (stage 4s) and INES99.3 (stage 4) (P<0.0001). Progression-free survival was poorer in patients whose tumours harboured SCA, in the whole population and in trials INES99.1 and INES99.2, in the absence of clinical symptoms (log-rank test, P=0.0001, P=0.04 and P=0.0003, respectively). In multivariate analysis, a SCA genomic profile was the strongest predictor of poorer progression-free survival.
In infants with stage 4s MYCN-non-amplified NB, a SCA genomic profile identifies patients who will require upfront treatment even in the absence of other clinical indication for therapy, whereas in infants with localised unresectable NB, a genomic profile characterised by the absence of SCA identifies patients in whom treatment reduction might be possible. These findings will be implemented in a future international trial.
Pathophysiologic platelet activation leads to thrombo-occlusive diseases such as myocardial infarction or ischemic stroke. Niemann-Pick C1 protein (NPC1) is involved in the regulation of lysosomal ...lipid trafficking and calcium ion (Ca2+) signaling, and its genetic mutation causes a lysosomal storage disorder. Lipids and Ca2+ are key players in the complex orchestration of platelet activation.
The present study aimed to determine the impact of NPC1 on Ca2+ mobilization during platelet activation in thrombo-occlusive diseases.
Using MK/platelet-specific knockout mice of Npc1 (Npc1Pf4∆/Pf4∆), ex vivo and in vitro approaches as well as in vivo models of thrombosis, we investigated the effect of Npc1 on platelet function and thrombus formation.
We showed that Npc1Pf4∆/Pf4∆ platelets display increased sphingosine levels and a locally impaired membrane-associated and SERCA3-dependent Ca2+ mobilisation compared to platelets from wildtype littermates (Npc1lox/lox). Further, we observed decreased platelet.
Our findings highlight that NPC1 regulates membrane-associated and SERCA3-dependent Ca2+ mobilization during platelet activation and that MK/platelet-specific ablation of Npc1 protects against experimental models of arterial thrombosis and myocardial or cerebral ischemia/reperfusion injury.
•Niemann-Pick C1 protein (NPC1) is involved in the regulation of lysosomal lipid trafficking.•We determined the impact of NPC1 on platelet activation and thrombo-occlusive diseases in mice.•NPC1 deficiency impairs platelet function by reducing calcium ion mobilization from the acidic stores.•Platelet-specific deletion of Npc1 protects mice against thrombo-occlusive diseases in vivo.
Abstract
Background
the European Union of Medical Specialists (UEMS-GMS) recommendations for training in Geriatric Medicine were published in 1993. The practice of Geriatric Medicine has developed ...considerably since then and it has therefore become necessary to update these recommendations.
Methods
under the auspices of the UEMS-GMS, the European Geriatric Medicine Society (EuGMS) and the European Academy of Medicine of Ageing (EAMA), a group of experts, representing all member states of the respective bodies developed a new framework for education and training of specialists in Geriatric Medicine using a modified Delphi technique. Thirty-two expert panel members from 30 different countries participated in the process comprising three Delphi rounds for consensus. The process was led by five facilitators.
Results
the final recommendations include four different domains: ‘General Considerations’ on the structure and aim of the syllabus as well as quality indicators for training (6 sub-items), ‘Knowledge in patient care’ (36 sub-items), ‘Additional Skills and Attitude required for a Geriatrician’ (9 sub-items) and a domain on ‘Assessment of postgraduate education: which items are important for the transnational comparison process’ (1 item).
Conclusion
the current publication describes the development of the new recommendations endorsed by UEMS-GMS, EuGMS and EAMA as minimum training requirements to become a geriatrician at specialist level in EU member states.
Employing the Bonn–Gatchina partial wave analysis framework (PWA), we have analyzed HADES data of the reaction p(3.5 GeV)+p→pK+Λ. This reaction might contain information about the kaonic cluster ...“ppK−” (with quantum numbers JP=0− and total isospin I=1/2) via its decay into pΛ. Due to interference effects in our coherent description of the data, a hypothetical K‾NN (or, specifically “ppK−”) cluster signal need not necessarily show up as a pronounced feature (e.g. a peak) in an invariant mass spectrum like pΛ. Our PWA analysis includes a variety of resonant and non-resonant intermediate states and delivers a good description of our data (various angular distributions and two-hadron invariant mass spectra) without a contribution of a K‾NN cluster. At a confidence level of CLs=95% such a cluster cannot contribute more than 2–12% to the total cross section with a pK+Λ final state, which translates into a production cross-section between 0.7 μb and 4.2 μb, respectively. The range of the upper limit depends on the assumed cluster mass, width and production process.
We present data on charged kaons (K±) and ϕ mesons in Au(1.23A GeV)+Au collisions. It is the first simultaneous measurement of K− and ϕ mesons in central heavy-ion collisions below a kinetic beam ...energy of 10A GeV. The ϕ/K− multiplicity ratio is found to be surprisingly high with a value of 0.52±0.16 and shows no dependence on the centrality of the collision. Consequently, the different slopes of the K+ and K− transverse-mass spectra can be explained solely by feed-down, which substantially softens the spectra of K− mesons. Hence, in contrast to the commonly adapted argumentation in literature, the different slopes do not necessarily imply diverging freeze-out temperatures of K+ and K− mesons caused by different couplings to baryons.
Previous reports in the literature describe that the crystallization of hexaphenyl carbodiphosphorane (CDPPh) from a variety of solvents gives a “bent” geometry for the P–C–P moiety as the ...solid-state molecular structure. However, a linear structure is observed when CDPPh is crystallized from benzene. Here, we report detailed spectroscopic and theoretical studies on the linear and bent structures. X-ray powder diffraction examinations show a phase transition of linear CDPPh upon the loss of co-crystallized benzene molecules, which is accompanied by the bending of the P–C–P unit. Studies on the linear and bent structures (i.e., X-ray powder diffraction, solid-state NMR, UV–vis spectroscopy, and IR spectroscopy) show significant differences in their properties. Investigations of the solid-state structures with density functional theory-based methods (PBE-D3) point toward subtle dispersion effects being responsible for this solvent-induced bond-bending isomerism in CDPPh.
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