Fifteen cases of chondrodysplasia characterized by disproportionate dwarfism occurred in the progeny of a single Holstein bull. A de novo mutation event in the germline of the sire was suspected as cause. Whole-genome sequencing revealed a single protein-changing variant in the stop codon of FGFR3 gene on chromosome 6. Sanger sequencing of EDTA blood proved that this variant occurred de novo and segregates perfectly with the observed phenotype in the affected cattle family. FGFR3 is an important regulator gene in bone formation owing to its key role in the bone elongation induced by FGFR3-dimers. The detected paternally inherited stop-lost variant in FGFR3 is predicted to add 93 additional amino acids to the protein's C-terminus. This study provides a second example of a dominant FGFR3 stop-lost variant as a pathogenic mutation of a severe form of chondrodysplasia. Even though FGFR3 is known to be associated with dwarfism and growth disorders in human and sheep, this study is the first to describe FGFR3-associated chondrodysplasia in cattle. © 2020 Stichting International Foundation for Animal Genetics.PURPOSE This study aimed to investigate the influence of diagnosis, body weight, sex, age, smoking, formulations, and concomitant drugs on steady-state dose-corrected serum concentrations (C/D) of venlafaxine (VEN) and O-desmethylvenlafaxine (ODV). METHODS A retrospective analysis of therapeutic drug monitoring (TDM) was carried out. Patients' demographic data, therapeutic regimens, and concentrations were collected. RESULTS We included 91 verified samples from 80 patients. Females had by average 13% smaller body weight, 50% higher C/D of VEN, and VEN + ODV and 25% smaller ODV/VEN than males. Patients >60 years had by average 33-59% higher C/D levels of ODV and VEN + ODV than younger patients. The concomitant use of valproic acid caused an average 51% higher C/D of ODV and a 2.2-fold larger ODV/VEN, while clozapine was related with 40% smaller ratio of ODV/VEN and 38% lower C/D levels of ODV. Positive correlations were detected between valproic acid concentrations and the C/D of VEN and VEN + ODV. In a multiple linear regression analysis, variance in the C/D of VEN + ODV was partly attributed to the daily dose of VEN, sex, age and valproic acid concentration. CONCLUSION Our results suggested daily dose of VEN, sex, age, and valproic acid as indicators for the C/D of VEN + ODV in Chinese patients. TDM as a valuable tool was suggested in elderly female patients and patients receiving polypharmacy. © 2020 John Wiley & Sons Ltd.Allylboration chemistry has provided very reliable tools to organic synthesis, but complex applications such as stereogenic fragment couplings have remained underexplored. We disclose a general synthesis of complex, trifunctionalized allylboronates and extensive investigations of their stereocontrolled transformations. A peculiar transition in stereocontrol from the polar Felkin-Anh (PFA) to the Cornforth-Evans (CE) model was observed for alkoxy- and epoxy-substituted aldehydes. CE-type transition states were uniformly identified in advanced, DFT-based computational studies of allylboration reactions of epoxy aldehydes, conforming well to the experimental data, and highlighting the underestimated relevance of this model. Furthermore, a mechanism-based rationale for the substitution pattern of the epoxide was delineated that ensures predictable stereocontrol and renders α,β-epoxy aldehydes generally applicable substrates for target synthesis. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Oxylipins constitute a family of oxidized fatty acids, that are well known as tissue hormones in mammals. They contribute to inflammation and its resolution. Major classes of these lipid mediators are inflammatory prostaglandins (PGs) and leukotrienes (LTs) as well as pro-resolving resolvins (Rvs). Understanding their biosynthetic pathways and modes of action is important for anti-inflammatory interventions. Besides mammals, also marine algae biosynthesize mammalian-like oxylipins and thereby offer new opportunities for oxylipin research. They provide prolific sources for these compounds and offer unique opportunities to study alternative biosynthetic pathways to the well-known lipid mediators. Herein, we discuss recent findings on the biosynthesis of oxylipins in mammals and algae including an alternative pathway to prostaglandin E2, a novel pathway to a precursor of leukotriene B4 as well as the production of resolvins in algae. We evaluate the pharmacological potential of the algal metabolites with implications in health and disease. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Fluorine's absence from most biomolecules renders it an excellent probe for NMR spectroscopy to monitor inhibitor-protein interactions. However, predicting the binding mode of a fluorinated ligand from a chemical shift (or vice versa) has been challenging due to the high electron density of the fluorine atom.  Nonetheless, reliable 19F chemical shift predictions to deduce ligand binding modes hold great potential for in silico drug design. Here, we present a systematic QM/MM study to predict the 19F NMR chemical shifts of a covalently bound fluorinated inhibitor to the essential oxidoreductase tryparedoxin (Tpx) from African trypanosomes, the causative agent of African Sleeping Sickness. We include many protein-inhibitor conformations as well as monomeric and dimeric inhibitor-protein complexes, thus rendering it the largest computational study on chemical shifts of 19F nuclei in a biological context to date. https://www.selleckchem.com/products/azd-1208.html Our predicted shifts agree well with those obtained experimentally and pave the way for future work in this area. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.BACKGROUND Meralgia paresthetica is a mononeuropathy of the lateral femoral cutaneous nerve. A common therapy is injection with corticosteroids. The goal of this study was to analyze the effect of injection with methylprednisolone/lidocaine vs placebo. METHODS After randomization, 10 patients received a nerve stimulator-guided injection with methylprednisolone/lidocaine, and 10 patients received saline. The primary outcome measure was pain (visual analogue scale, VAS). RESULTS In the placebo group, there was a significant pain reduction (baseline VAS, 6.8; VAS week 12, 4.3; P = .014). The VAS score in the methylprednisolone group did not show a significant reduction (baseline VAS, 7.4; VAS week 12, 4.8; P = .053). There was no significant difference in pain reduction between the groups. CONCLUSIONS We found no objective evidence for benefit from nerve stimulator-guided injection with corticosteroids in meralgia paresthetica, although this study is limited by a small sample size. Future placebo-controlled studies using ultrasound-guided injection are warranted.