Pituitary apoplexy of an giant prolactinoma during pregnancy
g., geographic distance, separation by water, population size) and internal (semantic density, salience) sources of variation. The results show that both external and internal factors contribute to variation, but that the exact role of each individual factor differs across semantic domains. These findings highlight the need to incorporate language-internal factors in studies on variation, as well as a need for more comprehensive analysis tools to help better understand its patterns.In this paper we evaluate two unsupervised approaches to denoise Magnetic Resonance Images (MRI) in the complex image space using the raw information that k-space holds. The first method is based on Stein's Unbiased Risk Estimator, while the second approach is based on a blindspot network, which limits the network's receptive field. Both methods are tested on two different datasets, one containing real knee MRI and the other consists of synthetic brain MRI. These datasets contain information about the complex image space which will be used for denoising purposes. Both networks are compared against a state-of-the-art algorithm, Non-Local Means (NLM) using quantitative and qualitative measures. For most given metrics and qualitative measures, both networks outperformed NLM, and they prove to be reliable denoising methods.Endeavors to computationally model language variation and change are ever increasing. While analyses of recent diachronic trends are frequently conducted, long-term trends accounting for sociolinguistic variation are less well-studied. Our work sheds light on the temporal dynamics of language use of British 18th century women as a group in transition across two situational contexts. Our findings reveal that in formal contexts women adapt to register conventions, while in informal contexts they act as innovators of change in language use influencing others. While adopted from other disciplines, our methods inform (historical) sociolinguistic work in novel ways. These methods include diachronic periodization by Kullback-Leibler divergence to determine periods of change and relevant features of variation, and event cascades as influencer models.The present study evaluates the crystal growth rate of amorphous drugs when dispersed in different ternary polymeric amorphous solid dispersions (ASDs) in the presence of surfactants. Specifically, ternary ASDs of aprepitant (APT, selected as a model drug) were prepared via melt-quench cooling by evaluating three commonly used ASDs matrix/carriers, namely hydroxypropyl cellulose (HPC), poly(vinylpyrrolidone) (PVP) and the copolymer Soluplus® (SOL), and two suitable surfactants, namely d-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS) and poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (P407). Results showed that all components were completely miscible (verified via hot stage polarized microscopy) and both surfactants were acting as plasticizers to the API. APT's crystal growth rate was increased in the presence of both P407 and TPGS, while PVP was identified as the matrix/carrier with the greatest impact API's crystal growth rate inhibition. Interestingly, TPGS presented a noticeable synergistic effect when combined with PVP resulting in a further reduction of APT's crystal growth rate. Furthermore, evaluation of APT's nucleation induction time in dissolution medium (PBS pH 6.8) revealed PVP as the most effective crystallization inhibitor, whereas the addition of TPGS showed to improve PVP's ability to inhibit APT's recrystallization. Finally, the formation of intermolecular interactions in the ternary APT-PVP-TPGS provided an explanation for the observed PVP-TPGS synergistic effects, with molecular dynamics simulations being able to unravel the type and extent of these interactions on a theoretical basis.A deep eutectic solvent (DES) is a eutectic system consisting of hydrogen bond donor and acceptor has been suggested as a promising formulation strategy for poorly soluble drugs. A DES consisting of choline chloride and levulinic acid in a 12 molar ratio was used to formulate a liquid solution of the model drug aprepitant. This formulation was tested in vitro (drug release and permeability) and in vivo (rat model) and compared with the performance of amorphous aprepitant and the commercial aprepitant nanocrystalline formulation. In this study a DES formulation is compared for the first time directly to other established enabling formulations. CDK inhibitor The in vitro drug release study demonstrated that the DES formulation and the amorphous form both were able to induce an apparent supersaturation followed by subsequent drug precipitation. To mitigate the risk of precipitation, HPMC was predissolved in the dissolution medium, which successfully reduced the degree of precipitation. In line with the results from the release study, an in vitro permeation study showed superior permeation of the drug from the DES formulation and from the amorphous form compared to the nanocrystalline formulation. However, the promising in vitro findings could not be directly translated into an increased in vivo performance in rats compared to the nanocrystalline formulation. Whilst the DES formulation (34 ± 4%) showed a higher oral bioavailability compared to amorphous aprepitant (20 ± 4%), it was on par with the oral bioavailability obtained from the nanocrystalline formulation (36 ± 2%).
Despite intensive research on the cytokine resistin only few studies investigated mother-newborn-pairs during healthy pregnancy and reported about interactions with clinical obstetric variables or other cytokines. Comparison of existing studies is difficult due to differences between assays, sample collection, gestational age, definition of healthy controls and patient characteristics. Furthermore, differences between rodent models and humans do not allow for a direct comparison.
In this cross-sectional, prospective study 109 healthy mother-newborn pairs were analyzed. Maternal venous blood samples were taken on admission to the labor ward; newborn venous blood samples were drawn from the placental part of the umbilical cord (UC), immediately after clamping. Resistin, leptin, adiponectin, TNF-α, IL-6 and brain derived neurotrophic factor (BDNF) serum concentrations were measured with commercially available immunoassays. Determinants of maternal and newborn resistin levels were analyzed using simple and multiple linear regression.