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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. Syrosingopine order 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. © 2020 Wiley Periodicals, Inc.Myelination is key to effective message passing in the central nervous system and is likely linked to the pathogenesis of schizophrenia (SZ). Emerging evidence indicates that a large portion of intracortical myelin insulates inhibitory interneurons that are highly relevant to pathogenesis of schizophrenia. Here for the first time, we characterized intracortical myelination across the entire cortical surface in first-episode treatment-naïve patients with schizophrenia (FES) using T1w/T2w ratio of structural MRI, FES patients exhibited significantly higher myelin content in the left inferior parietal lobe, supramarginal gyrus, and superior temporal gyrus in the superficial layer, as well as left IPL in the middle layer, but significantly lower myelin content in the left middle insula and posterior cingulate gyrus. Years of education, a proxy for onset of functional decline, significantly altered the relationship between abnormal parietal and posterior cingulate myelination and clinical symptoms, indicating that the pathoplastic role of myelination hinges on the age of onset of functional decline. In addition, higher myelination generally related to better cognitive function in younger subjects but worse cognitive function in older subjects. We conclude that FES is characterized by increased myelination of the superficial layers of the parietal-temporal association cortex, but reduced myelination of the cingulo-insular midcortical layer cortex. Intracortical myelin content affects both cognitive functioning and symptom burden in FES, with the effect conditional upon age and timing of onset of functional decline. These results suggest myelination might be a critical biological target for procognitive interventions in SZ. © 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.The male genitalia are a common site of dermatoses. Patients with penile diseases often delay or avoid medical care due to anxiety and embarrassment. In this narrative review we describe some of the main benign dermatoses localized to male genital, focusing on their epidemiology, clinical and dermoscopic features, as well as available therapies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Head motion during magnetic resonance imaging (MRI) induces image artifacts that affect virtually every brain measure. In parallel, cross-sectional observations indicate a correlation of head motion with age, psychiatric disease status and obesity, raising the possibility of a systematic artifact-induced bias in neuroimaging outcomes in these conditions, due to the differences in head motion. Yet, a causal link between obesity and head motion has not been tested in an experimental design. Here, we show that a change in body mass index (BMI) (i.e., weight loss after bariatric surgery) systematically decreases head motion during MRI. In this setting, reduced imaging artifacts due to lower head motion might result in biased estimates of neural differences induced by changes in BMI. Overall, our finding urges the need to rigorously control for head motion during MRI to enable valid results of neuroimaging outcomes in populations that differ in head motion due to obesity or other conditions. © 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.Cellular signaling via binding of the cytokines IL-36α, β and γ along with binding of the accessory protein IL-36RAcP, to their cognate receptor IL-36R is believed to play a major role in epithelial and immune cell mediated inflammation responses. Antagonizing the signaling cascade that results from these binding events via a directed monoclonal antibody provides an opportunity to suppress such immune responses. We report here the molecular structure of a complex between an extra-cellular portion of human IL-36R and a Fab derived from a high affinity anti-IL-36R neutralizing monoclonal antibody at 2.3å resolution. This structure, the first of IL-36R, reveals similarities with other structurally characterized IL-1R family members and elucidates the molecular determinants leading to the high affinity binding of the monoclonal antibody. The structure of the complex reveals that the epitope recognized by the Fab is remote from both the putative ligand and accessory protein binding interfaces on IL-36R, suggesting that the functional activity of the antibody is non-competitive for these binding events. This article is protected by copyright. All rights reserved. © 2020 The Protein Society.Mesenchymal stem cells (MSCs) are a major component of various forms of tissue engineering. MSCs have self-renewal and multidifferential potential. Osteogenic differentiation of MSCs is an area of attention in bone regeneration. One form of MSCs are adipose-derived stem cells (ASCs), which can be simply harvested and differentiated into several cell lineages, such as chondrocytes, adipocytes, or osteoblasts. Due to special properties, ASCs are frequently used in vitro and in vivo bone regeneration. Identifying factors involved in osteogenic differentiation of ASCs is important for better understanding the mechanism of osteogenic differentiation. Different methods are used to stimulate osteogenesis of ASCs in literature, including common osteogenic media, growth factors, hormones, hypoxia, mechanical and chemical stimuli, genetic modification, and nanotechnology. This review article provides an overview describing the isolation procedure, characterization, properties, current methods for osteogenic differentiation of ASCs, and their basic biological mechanism. © 2020 Wiley Periodicals, Inc.The enantioselective synthesis of α-thiocarboxylic acids via biocatalytic dynamic kinetic resolution (DKR) of nitrile precursors exploiting nitrilase enzymes is described. A panel of 35 nitrilase biocatalysts were screened and enzymes Nit27 and Nit34 were found to catalyze the DKR of racemic α-thionitriles under mild conditions, affording the corresponding carboxylic acids with high conversions and good-to-excellent ee. The ammonia produced in situ during the biocatalytic transformation favours the racemization of the nitrile enantiomers and, in turn, the DKR without the need of any external additive base. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Tear trough deformity is one of the most common cosmetic concerns when it comes to facial rejuvenation in the Indian population. It is seen in a wide age group from 20 years of age to over 70 years of age. The tear trough deformity is restricted to the tear trough in most younger people but as one ages, the tear trough deformity includes the entire region under the eye and is better known as the infraorbital hollow. Hyaluronic acid fillers have been the fillers of choice in the treatment of the tear trough nonsurgically. Many treatment techniques have been described in literature. Both needles and cannulas have been used with equal efficacy. The author chooses to use both the needle and cannula in the same session to treat tear trough for a better cosmetic outcome with lesser chances of side effects. © 2020 Wiley Periodicals, LLC.BACKGROUND Children with chronic kidney disease require specialist renal paediatric dietetic care, regardless of disease severity or geographical location; however, under-resourcing makes this challenging. Videoconsultation may offer a solution but research exploring its acceptability is limited. The present study explored parent/carer and child perspectives of videoconsultation as an alternative or supplement to existing regional dietetic care. METHODS Children and families using a regional paediatric nephrology service were recruited through purposeful sampling techniques. Renal paediatric dietitians used existing hospital software to host videoconsultations with families. Perspectives were subsequently explored in telephone interviews with the children, their parents and separately with the renal dietitians. Data were transcribed verbatim and an inductive framework analysis conducted. RESULTS Twelve families took part in the study, comprising 13 parents and five children (aged 9 months to 14 years). Two renal dietitians were also interviewed.
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