Advance Care Planning in der Psychiatrie

Definition of the problem

The term Advance Care Planning describes a concept of comprehensive planning for future health care situations that, amongst others, aims at supporting people to set up advance statements defining goals and desired directions of patient care, using qualified, prospective counseling offers. Another aim is to promote the dissemination and implementation of this concept with the help of structural, mostly regional measures.

Arguments

This article discusses Advance Care Planning in psychiatry. It visualizes different forms of psychiatric advance statements and reports legal regulations from the US, Great Britain and Germany. Furthermore, this article provides an overview of international studies on the implementation of Advance Care Planning in psychiatry. These studies impressively illustrate the need of qualified counseling- and supportive offers, as without such offers, advance statements are hardly implemented and noticed in practice.

Conclusion

Against this background, the authors recommend the experimental implementation of (regional) Advance Care Planning programs as pilot projects, aiming at ameliorating quality and acceptance of advance statements in psychiatry. These projects should be scientifically accompanied, evaluated and where necessary adjusted.

     

Synthesis,Characterization, Antibacterial Properties,and In Vitro Studies of Selenium and Strontium Co-Substituted Hydroxyapatite

In this study, as a measure to enhance the antimicrobial activity of biomaterials, the selenium ions have been substituted into hydroxyapatite (HA) at different concentration levels. To balance the potential cytotoxic effects of selenite ions (SeO₃²⁻) in HA, strontium (Sr²⁺) was co-substituted at the same concentration. Selenium and strontium-substituted hydroxyapatites (Se-Sr-HA) at equal molar ratios of x Se/(Se + P) and x Sr/(Sr + Ca) at (x = 0, 0.01, 0.03, 0.05, 0.1, and 0.2) were synthesized via the wet precipitation route and sintered at 900 °C. The effect of the two-ion concentration on morphology, surface charge, composition, antibacterial ability, and cell viability were studied. X-ray diffraction verified the phase purity and confirmed the substitution of selenium and strontium ions. Acellular in vitro bioactivity tests revealed that Se-Sr-HA was highly bioactive compared to pure HA. Se-Sr-HA samples showed excellent antibacterial activity against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus carnosus) bacterial strains. In vitro cell–material interaction, using human osteosarcoma cells MG-63 studied by WST-8 assay, showed that Se-HA has a cytotoxic effect; however, the co-substitution of strontium in Se-HA offsets the negative impact of selenium and enhanced the biological properties of HA. Hence, the prepared samples are a suitable choice for antibacterial coatings and bone filler applications.     

Effect of Soft Segment Length and Chain Extender Structure on Phase Separation and Morphology in Poly(urethane urea)s

The phase separation and morphology in poly(urethane urea)s were investigated as soft segment length and chain extender structure were varied. Increases in soft segment length led to increased phase separation that resulted in greater mobility of the soft segment. This was shown by lower soft segment glass transition temperatures in differential scanning calorimetry (DSC) as well as a shift of E_max″ and tan δ_max to lower temperatures. Also the structure of the chain extender affected the degree of phase separation and mixing of the soft and the hard blocks in an interphase. Atomic force microscopy (AFM) was used to visualize the structure of the phase‐separated domains. The hard domains were in the form of spheres 5–10 nm, or long needles 5 nm thick and 50–300 nm long. As the soft segment length increased, there were more pure soft segment phase areas between the hard domains. At high hard segment content, a larger scale structure was found, consisting of both hard and soft segments.

DSC thermograms of poly(urethane urea)s containing different soft segment lengths.     

Sulphide-induced deactivation of Pd/Al2O3 as hydrodechlorination catalyst and its oxidative regeneration with permanganate

Pd-based catalysts have become important in environmental catalysis for their ability to hydrodechlorinate a wide range of chlorinated organic contaminants in water under ambient conditions. The success of their application in the remediation practice, e.g. for groundwater treatment, is often hindered by the sensitivity of Pd to poisoning by sulphur compounds. In this study, the stability and sulphide-induced deactivation behaviour of a highly active Pd/Al₂O₃ catalyst was investigated. The specific activity of Pd for the hydrodechlorination of chlorobenzene corresponds to rate coefficients up to k_Pd = 350 L g⁻¹ min⁻¹. The totally deactivated catalyst, resultant of sulphide poisoning, was regenerated with potassium permanganate. The pH value, as a key parameter which may influence the degree of deactivation as well as the efficiency of catalyst regeneration, was evaluated. Results show that in clean water the Pd/Al₂O₃ catalyst showed no inherent deactivation regardless of the ageing time and the pH value of the catalyst suspension. The degree of catalyst poisoning effected by 1.8–5.4 μM sulphide, corresponding to molar ratios of S:Pd_surface = 1.5–8.5, was observed to be higher under neutral and alkaline than under acidic conditions. The exposure of the catalyst to higher sulphide concentration of 14.2 μM resulted in complete catalyst deactivation regardless of the pH conditions. However, the efficacy of permanganate as oxidative regenerant for the fouled catalyst showed strong pH-dependence. A regeneration time of 10–30 min at low pH was sufficient to recover completely the high catalytic activity of Pd/Al₂O₃ for the hydrodechlorination reaction.     

Bioelectrocatalytic properties of Agrocybe aegerita peroxygenase

A biosensor for detecting the aromatic substance 4-nitrophenol based on Agrocybe aegerita peroxygenase (AaP) immobilized with chitosan-stabilized gold nanoparticles is presented here. This biosensor measures the enzymatic product of 4-nitrophenol peroxygenation, 4-nitrocatechol, which is electrochemically detected in the presence of hydrogen peroxide. Cyclic voltammetry and amperometry were used to characterize the proposed biosensor. The linear range of the AaP biosensor for the detection of 4-nitrophenol was between 10 and 30 μM with a detection limit of 0.2 μM (based on the S/N = 3). The catalytic property of AaP to oxidize 4-nitrophenol was compared with two other heme proteins, a camphor-hydroxylating cytochrome P450 monooxygenase (P450_cam, CYP101) and horseradish peroxidase (HRP). The results revealed that only AaP is capable of catalyzing the hydroxylation of 4-nitrophenol into 4-nitrocatechol. Consequently, AaP could be a particularly potent biocatalyst that may fill the gap between cytochrome P450s and common heme peroxidases.     

Composites of polyamide 6 and silicate nanotubes of the mineral halloysite: Influence of molecular weight on thermal, mechanical and rheological properties

In this work, the potential of silicate nanotubes of the naturally occurring mineral halloysite as filler for polyamide 6 (PA 6) nanocomposites is evaluated. Several PA 6/halloysite composites with 0 wt% to 30 wt% filler loading using two different grades of PA 6 were prepared. In order to elucidate the influence of molecular weight on the properties of the nanocomposites, mechanical resp. rheological experiments (i) below the glass transition temperature T_g of PA 6, (ii) between T_g and the melting temperature T_m of PA 6 and (iii) above T_m were performed. Our investigations reveal that the addition of halloysite nanotubes favours the formation of the γ-modification for the low molar mass PA 6. Furthermore, the storage modulus, the tensile modulus and the yield stress of the composites increase with concentration of halloysite, an effect which is strongly pronounced at very low filler fractions for the low molar mass PA 6 composites. The increase of the storage modulus which was measured in dynamic-mechanical experiments is mostly dominant in the temperature interval from 55 °C to 100 °C, i.e. above the glass transition temperature of PA 6. Rheological investigations showed that the shear viscosity is only moderately increased by the addition of a low fraction of halloysite to PA 6, and nanocomposites with 30 wt% halloysite can be still processed. In summary, halloysite nanotubes are promising and inexpensive candidates for increasing the stiffness of PA 6 while maintaining very good flow properties.     

Rational Design of a Minimal and Highly Enriched CYP102A1 Mutant Library with Improved Regio‐, Stereo‐ and Chemoselectivity

Monooxygenase mutants : A minimal and highly enriched CYP102A1 mutant library was constructed by combining five hydrophobic amino acids in two positions. The library was screened with four different terpene substrates. Eleven variants demonstrated either a strong shift or improved regio‐ or stereoselectivity during oxidation of at least one substrate as compared to CYP102A1 wild type.

     

Strategien zur gezielten Verbesserung des anodenseitigen Elektronentransfers in mikrobiellen Brennstoffzellen

The concept of the microbial fuel cell (MFC) has existed for over 100 years, but only since the last decade its practical implementation in waste water treatment has been realized in scales up to 1000 L. This review article shows available strategies to increase the limiting extracellular electron transfer (EET) for anode space of MFCs. Therefore, organism‐based improvements as well as the effect of (bio)polymers and redox mediators on ETT will be demonstrated.     

From a library of MAG antagonists to nanomolar CD22 ligands

Siglec-2, also known as CD22, is involved in the regulation and survival of B-cells and has been successfully targeted in cell depletion therapies with antibody-based approaches. Sialic acid derivatives, already known to bind with high affinity to myelin-associated glycoprotein (MAG, Siglec-4), were screened for their binding affinity for CD22 by surface plasmon resonance. The best compound identified was further modified with various hydrophobic substituents at the 2-, 5-, and 9-positions of the sialic acid scaffold, leading to nanomolar derivatives, of which ligand 17 b shows the most promising pharmacodynamic and pharmacokinetic profiles. Isothermal titration calorimetry measurements demonstrate that the binding is enthalpy driven. Interestingly, the thermodynamic fingerprints reveal an excellent correlation between gains in enthalpy and compensation by increased entropy costs. Moreover, 17 b exhibits a residence time in the range of a few seconds, clearly prolonged relative to residence times typically observed for carbohydrate-lectin interactions. Finally, initial tests regarding drug-like properties of 17 b demonstrate the required high plasma protein binding yet a lack of oral availability, although its distribution coefficient (log D) is in the required range.     

FimH antagonists: structure-activity and structure-property relationships for biphenyl α-D-mannopyranosides

Urinary tract infections (UTIs) are caused primarily by uropathogenic Escherichia coli (UPEC), which encode filamentous surface‐adhesive organelles called type 1 pili. FimH is located at the tips of these pili. The initial attachment of UPEC to host cells is mediated by the interaction of the carbohydrate recognition domain (CRD) of FimH with oligomannosides on urothelial cells. Blocking these lectins with carbohydrates or analogues thereof prevents bacterial adhesion to host cells and therefore offers a potential therapeutic approach for prevention and/or treatment of UTIs. Although numerous FimH antagonists have been developed so far, few of them meet the requirement for clinical application due to poor pharmacokinetics. Additionally, the binding mode of an antagonist to the CRD of FimH can switch from an in‐docking mode to an out‐docking mode, depending on the structure of the antagonist. In this communication, biphenyl α‐D ‐mannosides were modified to improve their binding affinity, to explore their binding mode, and to optimize their pharmacokinetic properties. The inhibitory potential of the FimH antagonists was measured in a cell‐free competitive binding assay, a cell‐based flow cytometry assay, and by isothermal titration calorimetry. Furthermore, pharmacokinetic properties such as log D, solubility, and membrane permeation were analyzed. As a result, a structure–activity and structure–property relationships were established for a series of biphenyl α‐D ‐mannosides.