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Rebecca Robillard Karianne Dion Marie‐Helene Pennestri Elizaveta Solomonova Elliott Lee Mysa Saad Anthony Murkar Roger Godbout Jodi D. Edwards Lena Quilty Alexander R. Daros Raj Bhatla Tetyana Kendzerska 《Journal of sleep research》2021,30(1):e13231
This study aimed to evaluate changes in sleep during the COVID‐19 outbreak, and used data‐driven approaches to identify distinct profiles of changes in sleep‐related behaviours. Demographic, behavioural and psychological factors associated with sleep changes were also investigated. An online population survey assessing sleep and mental health was distributed between 3 April and 24 June 2020. Retrospective questions were used to estimate temporal changes from before to during the outbreak. In 5,525 Canadian respondents (67.1% females, 16–95 years old: Mean ± SD = 55.6 ± 16.3 years), wake‐up times were significantly delayed relative to pre‐outbreak estimates (p < .001, = 0.04). Occurrences of clinically meaningful sleep difficulties significantly increased from 36.0% before the outbreak to 50.5% during the outbreak (all p < .001, g ≥ 0.27). Three subgroups with distinct profiles of changes in sleep behaviours were identified: “Reduced Time in Bed”, “Delayed Sleep” and “Extended Time in Bed”. The “Reduced Time in Bed” and “Delayed Sleep” subgroups had more adverse sleep outcomes and psychological changes during the outbreak. The emergence of new sleep difficulties was independently associated with female sex, chronic illnesses, being employed, family responsibilities, earlier wake‐up times, higher stress levels, as well as heavier alcohol use and television exposure. The heterogeneity of sleep changes in response to the pandemic highlights the need for tailored interventions to address sleep problems. 相似文献
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Calwing Liao BSc Faezeh Sarayloo MSc Daniel Rochefort MSc Gabrielle Houle BSc Fulya Akçimen MSc Qin He PhD Alexandre D. Laporte MSc Dan Spiegelman MSc Werner Poewe MD Daniela Berg MD Stefanie Müller PhD Franziska Hopfner MD PhD Günther Deuschl MD PhD Gregor Kuhlenbäeumer MD PhD Alex Rajput MD Patrick A. Dion PhD Guy A. Rouleau MD PhD 《Movement disorders》2020,35(7):1153-1162
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Michelle Z. Dion Y. John Wang Daniel Bregante Wayman Chan Nisana Andersen Amy Hilderbrand Danielle Leiske Cleo M. Salisbury 《Journal of pharmaceutical sciences》2018,107(2):550-558
Protein oxidation is a major pathway for degradation of biologic drug products. Past literature reports have suggested that 2,2-azobis (2-amidinopropane) dihydrochloride (AAPH), a free radical generator that produces alkoxyl and alkyl peroxyl radicals, is a useful model reagent stress for assessing the oxidative susceptibility of proteins. Here, we expand the applications of the AAPH model by pairing it with a rapid peptide map method to enable site-specific studies of oxidative susceptibility of monoclonal antibodies and their derivatives for comparison between formats, the evaluation of formulation components, and comparisons across the stress models. Comparing the free radical–induced oxidation model by AAPH with a light-induced oxidation model suggests that light-sensitive residues represent a subset of AAPH-sensitive residues and therefore AAPH can be used as a preliminary screen to highlight molecules that need further assessment by light models. In sum, these studies demonstrate that AAPH stress can be used in multiple ways to evaluate labile residues and oxidation sensitivity as it pertains to developability and manufacturability. 相似文献
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Michelle Z. Dion Danielle Leiske Vikas K. Sharma Christina L. Zuch de Zafra Cleo M. Salisbury 《Pharmaceutical research》2018,35(11):222
Purpose
Biotherapeutics can be susceptible to oxidation during manufacturing and storage. Free L-methionine is known to protect methionine residues in proteins from oxidation. Similarly, free tryptophan and other indole derivatives have been shown to protect tryptophan residues from oxidation. N-acetyl-DL-tryptophan was previously identified as a potentially superior antioxidant to tryptophan as it has a lower oxidation potential and produces less peroxide upon light exposure. This study sought to confirm the antioxidant efficacy and safety of N-acetyl-DL-tryptophan and L-methionine as formulation components for biotherapeutic drugs.Methods
Antibodies were subjected to AAPH and light exposure in the presence of N-acetyl-DL-tryptophan and L-methionine. Oxidation in relevant CDR and Fc residues was quantified by peptide map. In silico, in vitro, and in vivo studies were performed to evaluate the safety of N-acetyl-DL-tryptophan and L-methionine.Results
Peptide mapping demonstrated that N-acetyl-DL-tryptophan was effective at protecting tryptophans from AAPH stress, and that the combination of N-acetyl-DL-tryptophan and L-methionine protected both tryptophan and methionine from AAPH stress. The safety assessment suggested an acceptable safety profile for both excipients.Conclusions
N-acetyl-tryptophan and L-methionine effectively reduce the oxidation of susceptible tryptophan and methionine residues in antibodies and are safe for use in parenteral biotherapeutic formulations.7.
A nephelometric immunoassay was developed to quantify immunoglobulin A (IgA) in children's stools. This method enables IgA in faecal protein extracts to be measured over a large range of concentrations (1.61-51.50 mg/L) with good accuracy (linear recovery in dilution-overloading assay) and precision (within- and between-run coefficients of variation (CVs) of 1-6%). An excellent recovery (105%) was obtained in stool samples overloaded by purified colostral IgA, demonstrating that the method used for faecal IgA extraction is adapted, not to induce significant IgA degradation, and probably allow a complete extraction of IgA. The amount of faecal IgA, as determined in stool samples from 125 children (6-24 months old), was an average of 14 mg per 100 g of stools (about 10% of the total protein stool content), with large individual variation (3-30 mg per 100 g of stools). No correlation was observed between faecal IgA amounts and the children's age or sex. Such an immunoassay could enable exhaustive noninvasive investigations of the maturation of the intestinal immune system, as well as accurate studies of the effect of oral dietary supplementation on IgA regulation. 相似文献
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Objective: To evaluate cardiac performance following coronary artery surgery using two different techniques of cardioplegia¶Design: Randomized prospective study¶Setting: Adult cardiothoracic intensive care unit in a university hospital¶Study population: Thirty patients undergoing isolated coronary surgery¶Interventions: Patients were randomized to receive either intermittent antegrade warm blood cardioplegia with normothermic bypass (group 1) or combined antegrade and retrograde cold crystalloid cardioplegia with hypothermic bypass (group 2). Hemodynamic evaluation included conventional measurements from a pulmonary artery catheter and data obtained by thermal dye dilution utilizing an arterial thermistor-tipped fiberoptic catheter¶Results: The only major difference between groups was a significantly higher right atrial pressure in group 2, from 4 h to 24 h after surgery (8.8 ± 2.6 vs. 11.8 ± 3.2 mmHg at 4 h and 11 ± 3.1 vs. 8.5 ± 1.8 mmHg at 24 h, P = 0.04). After cold cardioplegia a significant increase in right atrial pressure was observed (7.5 ± 3.1 before surgery vs. 11.4 ± 3 mmHg at 8 h, P = 0.003) whereas right ventricular end diastolic volume index did not increase significantly, suggesting impaired right ventricular diastolic compliance in this group¶Conclusions: Until 24 h after surgery cold cardioplegia is associated with impaired right ventricular filling, which seems better preserved by intermittent antegrade warm blood cardioplegia. End-diastolic volume measurement with the double-indicator technique allows differentiation between systolic and diastolic dysfunction. 相似文献