6) mL. Four bleeds were reported postsurgery; three were successfully treated with turoctocog alfa pegol (one was not evaluated). On the day of surgery, overall mean (median) dose was 75.5 (74.5) IU/kg and mean (median) number of doses was 1.7 (2.0). Five procedures required 11 transfusions on the day of surgery or days 1-6. No safety concerns or inhibitors were identified. Forty-five minor surgeries in 23 children were performed without complications. CONCLUSION Turoctocog alfa pegol was effective for perioperative haemostatic management of major and minor surgeries in patients across age groups with severe haemophilia A. © 2020 The Authors. Haemophilia published by John Wiley & Sons Ltd.Shwachman-Diamond syndrome (SDS) is an autosomal recessive multisystem disorder characterized by exocrine pancreatic dysfunction, bone marrow failure, and leukemia predisposition. Approximately 90% of cases are due to biallelic mutations in the Shwachman-Bodian-Diamond (SBDS) gene. Additional phenotypic features variably associated with SDS include skeletal, neurologic, hepatic, cardiac, endocrine, and dental abnormalities. We report five subjects with SDS who developed a range of inflammatory manifestations. Three patients developed inflammatory eye conditions. Single cases of juvenile idiopathic arthritis, chronic recurrent multifocal osteomyelitis, and scleroderma were also noted. Clinical presentation and treatment responses are described. Proteomic analysis revealed increased inflammatory signatures in SDS subjects as compared to controls. Treatment of inflammatory manifestations in patients with SDS may be complicated by potential myelosuppressive toxicities of anti-rheumatic medications. Further research is needed to better understand the potential link between inflammatory disorders and SDS to inform effective treatment strategies. © 2020 Wiley Periodicals, Inc.Alkylation of homofullerene [6,6]-C60(CF2)2- dianion with the set of alkyl halides, RX, was established to demonstrate an effect of RX nature on the conversion, product composition, and regioselectivity. The respective C60(CF2)RH, C60(CF2)R2 and C60(CF2)R ‘R ” compounds were obtained in the reaction with sterically unhindered RX, isolated by HPLC and unequivocally characterized. The kinetic studies evidenced SN2 mechanism for both alkylation steps, yielding mono- and dialkylated C60(CF2), respectively, and indicated the negative charge localization at the bridgehead carbon atoms as well as a steric hindrance of the CF2 moiety likely to be a key factors for the S N 2 reaction mechanism and observed regioselectivity. The significant difference in the rate constants of the first and the second steps is attributed to the different activation barriers predicted by DFT calculations which makes possible to develop synthetic methods for the regioselective preparation of monoalkylated C60(CF2)RH and heterodialkylated C60(CF2)R’R” derivatives. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Numerical methods for solving the cardiac electrophysiology model, which describes the electrical activity in the heart, are proposed. The model problem consists of a non-linear reaction-diffusion partial differential equation coupled to systems of ordinary differential equations that describes electrochemical reactions in cardiac cells. The proposed methods combine an operator splitting technique for the reaction-diffusion equation with primal hybrid methods for spatial discretization considering continuous or discontinuous approximations for the Lagrange multiplier. A static condensation is adopted to form a reduced global system in terms of the multiplier only. Convergence studies exhibit optimal rates of convergence and numerical experiments show that the proposed schemes can be more efficient than standard numerical techniques commonly used in this context when preconditioned iterative methods are used for the solution of linear systems. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.The first observations of altered metabolism in malignant cells were made nearly 100 years ago and therapeutic strategies targeting cell metabolism have been in clinical use for several decades.  In this review, we summarize our current understanding of cell metabolism dysregulation in childhood acute lymphoblastic leukemia (cALL). Larotrectinib chemical structure Reprogramming of cellular bioenergetic processes can be expected in the three distinct stages of cALL at diagnosis, during standard chemotherapy, and in cases of relapse. Upregulation of glycolysis, dependency on anaplerotic energy sources, and activation of the electron transport chain have all been observed in cALL. While the current treatment strategies are tackling some of these aberrations, cALL cells are likely to be able to rewire their metabolism in order to escape therapy, which may contribute to a refractory disease and relapse. Finally, here we focus on novel therapeutic approaches emerging from our evolving understanding of the alterations of different metabolic networks in lymphoblasts. © 2020 Wiley Periodicals, Inc.Guanylyl cyclase C (GC-C) is the receptor for the heat-stable enterotoxin, which causes diarrhea, and the endogenous ligands, guanylin and uroguanylin. GC-C is predominantly expressed in the intestinal epithelium and regulates fluid and ion secretion in the gut. The receptor has a complex domain organization, and in the absence of structural information, mutational analysis provides clues to mechanisms of regulation of this protein. Here, we review the mutational landscape of this receptor that reveals regulatory features critical for its activity. We also summarize the available information on mutations in GC-C that have been reported in humans and contribute to severe gastrointestinal abnormalities. Since GC-C is also expressed in extra-intestinal tissues, it is likely that mutations thus far reported in humans may also affect other organ systems, warranting a close observation of these patients in future. © 2020 International Union of Biochemistry and Molecular Biology.In obstetrics we often prioritize studying neonatal over maternal outcomes. Effects of anaemia in pregnancy are no different. ACOG recommends screening all women for anaemia and treating with iron supplementation, based primarily on improving infant outcomes. This article is protected by copyright. All rights reserved.