Reaction dynamics and residue identification of haemoglobin modification by acrolein, a lipid-peroxidation by-product.

BACKGROUND: Lipid hydroperoxides decompose to reactive aldehydes, such as acrolein. Measurement of oxidative stress markers in the clinic could improve risk stratification for patients. METHODS: To aid the development of diagnostic oxidative stress markers, we defined the acrolein modifications of haemoglobin using mass spectrometry. RESULTS: Acrolein modifications have little effect on the secondary structure of haemoglobin. They do not disrupt the quaternary structure, but instead promote crosslinked octamers. For acrolein modified haemoglobin the response to O2 binding is altered such that cooperativity is lost. Mass spectrometry experiments at a 1:1 acrolein:haemoglobin molar ratio demonstrate that the α-chain quickly forms an aza-Michael adduct (+56 Da), which then forms a more stable adduct, Nε-(3-methylpyridinium)lysine (MP-lysine, +76 Da) over 7 days. The ß-chain remains relatively unchanged over the duration of the 7 days and the aza-Michael adduct is dominant. At 2:1 and 5:1 molar ratios the α-chain was consistently modified at K7, H20, H50, and the ß-chain at C93 and H97 with the aza-Michael adduct. Beyond 5 h, an MP-adduct (+76 Da) was located predominantly at K7 of the α-chain, while an FDP-adduct (+94 Da) was observed at K95 of the ß-chain. CONCLUSIONS: We have generated qualitative evidence identifying the acrolein target sites on haemoglobin, a potential oxidative stress marker that is easily measured in circulation. GENERAL SIGNIFICANCE: We provide data for the community to develop targeted mass spectrometric or immunometric assays for acrolein modified haemoglobin to further validate the potential of haemoglobin as an oxidative stress marker in patients .

Global health classroom: mixed methods evaluation of an interinstitutional model for reciprocal global health learning among Samoan and New Zealand medical students.

BACKGROUND: Global health education partnerships should be collaborative and reciprocal to ensure mutual benefit. Utilisation of digital technologies can overcome geographic boundaries and facilitate collaborative global health learning. Global Health Classroom (GHCR) is a collaborative global health learning model involving medical students from different countries learning about each other's health systems, cultures, and determinants of health via videoconference. Principles of reciprocity and interinstitutional partnership informed the development of the GHCR. This study explores learning outcomes and experiences in the GHCR between students from New Zealand and Samoa. METHODS: This study used a mixed methods approach employing post-GHCR questionnaires and semi-structured face-to-face interviews to explore self-reported learning and experiences among medical students in the GHCR. The GHCR collaboration studied was between the medical schools at the University of Otago, New Zealand and the National University of Samoa, Samoa. RESULTS: Questionnaire response rate was 85% (74/87). Nineteen interviews were conducted among New Zealand and Samoan students. Students reported acquiring the intended learning outcomes relating to patient care, health systems, culture, and determinants of health with regards to their partner country. Interview data was indicative of attitudinal changes in relation to cultural humility and curiosity. Some reported a vision for progress regarding their own health system. Students in the GHCR reported that learning with their international peers in the virtual classroom made learning about global health more real and tangible. The benefits to students from both countries indicated reciprocity. CONCLUSIONS: This study demonstrates GHCR to be a promising model for collaborative and reciprocal global health learning using a student-led format and employing digital technology to create a virtual classroom. The self-reported learning outcomes align favourably with those recommended in the literature. In view of our positive findings, we present GHCR as an adaptable model for equitable, collaborative global health learning between students in internationally partnered institutions.

Paediatric presentations to Christchurch Hospital Emergency Department during COVID-19 lockdown.

AIM: To describe the variation in volumes and types of paediatric presentations to a tertiary emergency department in New Zealand during the national level 4 lockdown for COVID-19. METHODS: A retrospective, comparative cohort study in Christchurch Hospital Emergency Department, New Zealand. RESULTS: There was a 37% reduction in all emergency presentations during the 33-day lockdown period. Paediatric presentations reduced significantly more than non-paediatric presentations (53% paediatric vs. 34% non-paediatric, P < 0.00001). The decrease in both overall and paediatric presentations was significantly different than similar periods in 2019 and 2018 (P < 0.00001). The proportion of New Zealand European paediatric presentations during lockdown increased by 6.09% (P = 0.01), while Pacific peoples decreased by 3.36% (P = 0.005). The proportion of <1-year-old presentations increased by 5.56% (P = 0.001), while 11-15 years decreased by 7.91% (P = 0.0001). Respiratory-related paediatric presentations decreased by 30% and proportional decreased by 4.92% (P = 0.001). CONCLUSION: This study has identified a significant reduction in paediatric presentations to a tertiary emergency department in New Zealand during the national Alert Level 4 Lockdown for COVID-19. The proportional increase in the <1-year-old group may suggest a greater need for community-based child health services during the COVID-19 pandemic. Mental health support services may also need to adapt and expand to provide adequate psychological support for children during this crisis. Recognising the needs of these vulnerable groups will be critical during the ongoing COVID-19 pandemic in addition to informing response plans for similar events in the future.