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Malvidin protection against LPS-induced inflammation was coupled with a decline in the levels of nitric oxide metabolite and malondialdehyde, along with an increase in the ferric reducing antioxidant power, total thiol activity, and also superoxide dismutase and glutathione peroxidase activity. In accordance with this finding, malvidin may represent a promising therapeutic agent for the prevention of inflammation in PBMCs. © 2020 International Union of Biochemistry and Molecular Biology.PURPOSE To evaluate the dosimetric differences between photon intensity-modulated radiation therapy (IMRT) plans, 3D conformal proton therapy (3DCPT), and intensity-modulated proton therapy (IMPT) plans and to investigate the dosimetric impact of different beam spot size and beam apertures in IMPT for pediatric Ewing sarcoma of the chest wall. METHODS AND MATERIALS Six proton pediatric patients with Ewing sarcoma in the upper, middle, and lower thoracic spine regions as well as upper lumbar spine region were treated with 3DCPT and retrospectively planned with photon IMRT and IMPT nozzles of different beam spot sizes with/without beam apertures. The plan dose distributions were compared both on target conformity and homogeneity, and on organs-at-risk (OARs) sparing using QUANTEC metrics of the lung, heart, liver, and kidney. The total integral doses of healthy tissue of all plans were also evaluated. RESULTS Target conformity and homogeneity indices are generally better for the IMPT plans with beam aperture. Doses to the lung, heart, and liver for all patients are substantially lower with the 3DPT and IMPT plans than those of IMRT plans. In the IMPT plans with large spot without beam aperture, some OAR doses are higher than those of 3DCPT plans. The integral dose of each photon IMRT plan ranged from 2 to 4.3 times of proton plans. CONCLUSION Compared to IMRT, proton therapy delivers significant lower dose to almost all OARs and much lower healthy tissue integral dose. Compared to 3DCPT, IMPT with small beam spot size or using beam aperture has better dose conformity to the target. © 2020 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.INTRODUCTION The benefits of physical activity (PA) for people with haemophilia (PWH) may include improvements in joint, bone and muscle health. However, the factor VIII activity level required to avoid a bleeding episode associated with PA is unknown. AIM To elicit the opinion of clinical experts on the minimum level and ideal factor VIII activity ('level') required to avoid a bleeding episode during participation in different types of PA for PWH. METHODS Based on the 2017 National Hemophilia Foundation PA descriptions, clinical experts estimated a minimally acceptable and an ideal factor level at which a bleed could be avoided. The uncertainty around estimates was quantified using an approach to construct a probability distribution to represent expert opinion. RESULTS Minimum and ideal factor level increased with higher risk PA, whether or not joint morbidity was present, as did the experts' uncertainty in their estimates (ie the range between lowest and highest estimates for minimum and ideal levels). Mean minimum levels ranged from 4% to 48% for low to high risk for people without joint morbidity, and from 7% to 47% for those with joint morbidity. For ideal factor levels, corresponding figures were 9%-52% and 12%-64%, respectively. CONCLUSION To support a patient-centric outcome, expert opinion indicates that the clinical norm of 0.01 IU/mL (1%) trough level is insufficient. It is anticipated that introducing a more targeted approach to meet the needs of patients who are increasingly physically active will benefit patients further in addition to recent treatment advances. © 2020 John Wiley & Sons Ltd.AIM Haemophilia A (HA) is a male-predominant disorder, yet women and girls can have factor VIII (FVIII) deficiency with bleeding events requiring treatment. This study aimed to identify and characterize female patients with HA. METHODS Administrative claims dated 01 January 2012-31 July 2016 were accessed for patients with 18 months' coverage by commercial or Medicare Advantage with Part D insurance. Patients were included by HA diagnoses or treatments and/or bleeding-related diagnoses or procedures, and excluded by haemophilia B or qualitative platelet disorder diagnoses. A sample of charts was examined for bleeding history, HA therapies and bleeding treatments. All-cause healthcare utilization and costs were also described. RESULTS Among 353 patients meeting initial inclusion criteria, 86 charts were procured, with 8 patients identified as having HA. RMC-4550 ic50 Their mean age was 60 ± 17 years and most were Medicare-insured. The mean Charlson Comorbidity Index score was 2.50 ± 2.56; the most prevalent comorbid conditions involved coagulation/haemorrhage, fluid/electrolyte balance and non-traumatic joint disorders. Over 18 months, a mean of 54 ambulatory visits and 120 pharmacy fills were observed; mean medical costs were $86 694 and pharmacy costs were $25 396. CONCLUSIONS Identifying females with HA is challenging using healthcare claims, because diagnostic nomenclature is unclear for female patients treated for bleeding events. Although chart abstraction enhanced claims data, very few female patients were identified with HA. Nevertheless, even in a small sample, sizeable burden in comorbidity and healthcare use was observed. Improved nomenclature and coding for HA diagnoses for women and girls is key to improving research and treatment. © 2020 John Wiley & Sons Ltd.In less than six months, COVID-19 has spread from a marketplace in Wuhan, China to over 150 countries and territories of the world. Therapeutics are desperately needed to reduce the morbidity and mortality of this pandemic disease. It has been reported that hydroxychloroquine (HCQ) is active against SARS-CoV-2 in vitro, and this finding was quickly supported by an open label non-randomized clinical trial that provided the first published clinical evidence HCQ may be a treatment option. This article is protected by copyright. All rights reserved.The substrate promiscuity of microbial transglutaminase (mTG) has been exploited in various applications in biotechnology, in particular for the attachment of alkyl amines to glutamine-containing peptides and proteins. Here we expand the substrate repertoire to include hydrazines, hydrazides, and alkoxyamines, resulting in the formation of isopeptide bonds with varied susceptibilities to hydrolysis or exchange by mTG. Furthermore, we demonstrate that simple unsubstituted hydrazine and dihydrazides can be used to install reactive hydrazide handles onto the side chain of internal glutamine residues. The distinct hydrazide handles can be further coupled with carbonyls, including ortho-carbonylphenylboronic acids, to form site-specific and functional bioconjugates with tunable hydrolytic stability. The extension of the substrate scope of mTG beyond canonical amines thus substantially broadens the versatility of the enzyme, providing a new approach to facilitate novel applications. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.PURPOSE In this study, we developed a simple but useful computer program, called TomoMQA, to offer an automated quality assurance for mega-voltage computed tomography (MVCT) images generated via helical tomotherapy. METHODS TomoMQA is written in MATLAB and contains three steps for analysis (a) open the DICOM dataset folder generated via helical tomotherapy (i.e., TomoTherapy® and Radixact™), (b) call the baseline data for the consistency test and click the "Analysis" button (or click the "Analysis" button without the baseline data and export the results as the baseline data), and (c) print an analyzed report. The overall procedure for the QA analysis included in TomoMQA is referred from the TG-148 recommendation. Here, the tolerances for MVCT QA were implemented from TG-148 recommended values as default; however, it can be modified by a user manually. RESULTS To test the performance of the TomoMQA program, 15 MVCTs were prepared from five helical tomotherapy machines (1 of TomoTherapy® HD, 2 of TomoTherapy® HDA, and 2 of Radixact™) in 3 months and the QA procedures were performed using TomoMQA. From our results, the evaluation revealed that the developed program can successfully perform the MVCT QA analysis irrespective of the type of helical tomotherapy equipment. CONCLUSION We successfully developed a new automated analysis program for MVCT QA of a helical tomotherapy platform, called TomoMQA. The developed program will be made freely downloadable from the TomoMQA-dedicated website. © 2020 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.BACKGROUND Emerging evidence indicated that sleep characteristics may play important roles in the development of metabolic disorders. However, little is known as to the association between bedtime and the risk of non-alcoholic fatty liver disease (NAFLD) in individuals with pre-diabetes and diabetes. METHODS In a prospective cohort of 10 375 adults aged ≥40 years, 1960 of 3484 eligible pre-diabetic and diabetic individuals were identified for the current study. NAFLD was diagnosed using liver ultrasonography at baseline and at follow-up. Information on bedtime was obtained at baseline using a standard questionnaire. RESULTS We documented 433 incident cases of NAFLD among this study population. In multivariable-adjusted logistic regression model, later bedtime was associated with increased risk of NAFLD (29% increased risk per hour of later bedtime). Compared to individuals with bedtime ≤2000, the odds ratios (95% confidence intervals) of NAFLD for bedtime of 2000-2200 and ≥2200 were 1.56 (1.04-2.34) and 2.05 (1.31-3.20), respectively. In the subgroup analysis, significant associations were observed among those who were overweight or physically inactive, or those with metabolic syndrome or elevated 10-year risks for atherosclerotic cardiovascular disease. When estimating the joint effect of bedtime and other sleep characteristics, higher risk of incident NAFLD was observed in groups of late bed/early rise, late bed/napping (yes), late bed/bad sleeper, or late bed/shorter sleep durations. CONCLUSIONS Later bedtime was significantly associated with an increased risk of incident NAFLD in adults with pre-diabetes and diabetes, underscoring the importance of sleep behaviour management in the prevention of NAFLD. © 2020 John Wiley & Sons Ltd.Lithium (Li) bond, which is an analogue of hydrogen (H) bond, is supposed to have similar characteristics and functions as H bond. Simultaneously, the metallic nature and large radius of Li afford Li bond with special features. As one of the most important applications of Li element, Li batteries can afford emerging opportunities for the exploration of Li bond chemistry. In this contribution, the general historical development and the concept of Li bond are reviewed. Then a hopeful perspective of the application of Li bond in Li batteries is presented. This viewpoint renders a comprehensive understanding of Li bond in Li batteries and also an outlook of its future development. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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