Chronic Kidney Disease and Pregnancy. Guideline of the DGGG, OEGGG, DGfN (S2k Level, AWMF Registry No. 015 - 090).

Aim As diagnostic and therapeutic options have improved in recent years, women with limited renal function of varying etiologies are now able to become pregnant. Depending on the extent of disease and the patients' comorbidities, the care of these women can be especially challenging. This guideline aims to improve the interdisciplinary care offered to pregnant women with kidney disease. Methods A selective literature search was carried out. This S2k guideline was then compiled using a structured consensus-based process which included representatives from different medical specialties and professional societies. Recommendations Recommendations for the care of pregnant women with renal disease were developed to cover preconception counseling, the recording of risks, special aspects of prenatal care and prenatal screening, as well as the specific treatment options for the underlying disease in women wanting to have children and pregnant women.

Assessing the spatial scale of context effects: The example of neighbourhoods' educational composition and its relevance for individual aspirations.

The neighbourhood environment has repeatedly proven to be a relevant context for central aspects of individuals' lives, such as educational attainment. The conventional approach of measuring neighbourhood characteristics within disjunct geographical units fixed at a particular scale is less suitable for representing the characteristics of individual action spaces in everyday activities and for detecting scale-dependent relationships. We, therefore, adapted an ego-centred context approach by aggregating contextual characteristics within (approximately) circular areas around individual respondents' places of residence (ego-hoods). We also used an analytical framework that considers the quality of hierarchical context effects. This allowed us to derive conclusions about the spatial reference of micro-level mechanisms from the scale of context effects observed as a macro-micro relationship. We linked contextual indicators to individual-level data from the German Socio-Economic Panel. Comparing ego-hoods of different ranges, we confirmed the expectation of distance decay in the relevance of neighbours for individual educational aspirations.

Ugi Reaction-Derived α-Acyl Aminocarboxamides Bind to Phosphatidylinositol 3-Kinase-Related Kinases, Inhibit HSF1-Dependent Heat Shock Response, and Induce Apoptosis in Multiple Myeloma Cells.

Heat shock transcription factor 1 (HSF1) has been identified as a therapeutic target for pharmacological treatment of multiple myeloma (MM). However, direct therapeutic targeting of HSF1 function seems to be difficult due to the shortage of clinically suitable pharmacological inhibitors. We utilized the Ugi multicomponent reaction to create a small but smart library of α-acyl aminocarboxamides and evaluated their ability to suppress heat shock response (HSR) in MM cells. Using the INA-6 cell line as the MM model and the strictly HSF1-dependent HSP72 induction as a HSR model, we identified potential HSF1 inhibitors. Mass spectrometry-based affinity capture experiments with biotin-linked derivatives revealed a number of target proteins and complexes, which exhibit an armadillo domain. Also, four members of the tumor-promoting and HSF1-associated phosphatidylinositol 3-kinase-related kinase (PIKK) family were identified. The antitumor activity was evaluated, showing that treatment with the anti-HSF1 compounds strongly induced apoptotic cell death in MM cells.

One-pot Ugi/Aza-Michael synthesis of highly substituted 2,5-diketopiperazines with anti-proliferative properties.

The well-known Ugi reaction of aldehydes with amines, carboxylic acids and isocyanides leads to the formation of acyclic α-acylaminocarboxamides. Replacement of the carboxylic acid derivatives with ß-acyl substituted acrylic acids gives access to highly substituted 2,5-diketopiperazines in one single reaction-step without additives or complex reaction procedures. The obtained diketopiperazines show anti-proliferative effects on activated T cells and represent therefore potential candidates for targeting unwanted T cell-mediated immune responses.

Valeriana wallichii root extracts and fractions with activity against Leishmania spp.

Leishmanial diseases, posing a public health problem worldwide, are caused by Leishmania parasites with a dimorphic life cycle alternating between the promastigote and amastigote forms. Promastigotes transmitted by the vector are transformed into amastigotes residing in the host tissue macrophages. Presently, new antiparasitic agents are needed against Leishmania donovani and Leishmania major, the respective organisms causing visceral and cutaneous leishmaniasis, since the available treatments are unsatisfactory due to toxicity, high cost, and emerging drug resistance. Over the years, traditional medicinal flora throughout the world enriched the modern pharmacopeia. Hence, roots of 'Indian Valerian' (Valeriana wallichii DC) were studied for its antileishmanial activity for the first time. The methanol and chloroform extracts showed activity against L. donovani promastigotes and both promastigotes and amastigotes of L. major. The most active fraction, F3, obtained from the chloroform extract, showed IC(50) at ∼ 3-7 µg/ml against both the promastigotes and 0.3 µg/ml against L. major amastigotes. On investigation of the mechanism of cytotoxicity in L. donovani promastigotes, the 'hall-mark' events of morphological degeneration, DNA fragmentation, externalization of phosphatidyl serine, and mitochondrial membrane depolarization indicated that F3 could induce apoptotic death in leishmanial cells. Therefore, the present study revealed a novel and unconventional property of V. wallichii root as a prospective source of effective antileishmanial agents.

Advantages of synthesizing trans-1,2-cyclohexanediol in a continuous flow microreactor over a standard glass apparatus.

Comparison is made between the preparation of trans-1,2-cyclohexanediol in standard glassware (conventional batch production) and in a microreactor (continuous flow production). The reaction sequence involved two exothermic steps where the standard procedure demands slow reagent addition and careful temperature control. In the microreactor, the reaction could be carried out safely with up to 3 times higher reagent concentration. Synthetic benefits were a faster reaction rate and a higher purity product free of colored impurities (a feature of the batch procedure).