In vitro embryo production (IVP) suffers from excessive developmental failure. Its inefficiency is linked, in part, to reactive oxygen species (ROS) brought on by high ex vivo oxygen (O(2)) tensions. To further delineate the effects of ROS on IVP, the intracellular ROS levels of early bovine embryos were modulated by: (1) varying O(2) tension; (2) exogenous H(2)O(2) treatment; and (3) antioxidant supplementation. Although O(2) tension did not significantly affect blastocyst frequencies (P>0.05), 20% O(2) accelerated the rate of first cleavage division and significantly decreased and increased the proportion of permanently arrested 2- to 4-cell embryos and apoptotic 9- to 16-cell embryos, respectively, compared with embryos cultured in 5% O(2) tension. Treatment with H(2)O(2), when applied separately to oocytes, zygotes, 2- to 4-cell embryos or 9- to 16-cell embryos, resulted in a significant (P<0.05) dose-dependent decrease in blastocyst development in conjunction with a corresponding increase in the induction of either permanent embryo arrest or apoptosis in a stage-dependent manner. Polyethylene glycol-catalase supplementation reduced ROS-induced embryo arrest and/or death, resulting in a significant (P<0.05) increase in blastocyst frequencies under high O(2) culture conditions. Together, these results indicate that intracellular ROS may be signalling molecules that, outside an optimal range, result in various developmentally regulated modes of embryo demise.

The in vitro production of mammalian embryos suffers from high frequencies of developmental failure due to excessive levels of permanent embryo arrest and apoptosis caused by oxidative stress. The p66Shc stress adaptor protein controls oxidative stress response of somatic cells by regulating intracellular ROS levels through multiple pathways, including mitochondrial ROS generation and the repression of antioxidant gene expression. We have previously demonstrated a strong relationship with elevated p66Shc levels, reduced antioxidant levels and greater intracellular ROS generation with the high incidence of permanent cell cycle arrest of 2–4 cell embryos cultured under high oxygen tensions or after oxidant treatment. The main objective of this study was to establish a functional role for p66Shc in regulating the oxidative stress response during early embryo development. Using RNA interference in bovine zygotes we show that p66Shc knockdown embryos exhibited increased MnSOD levels, reduced intracellular ROS and DNA damage that resulted in a greater propensity for development to the blastocyst stage. P66Shc knockdown embryos were stress resistant exhibiting significantly reduced intracellular ROS levels, DNA damage, permanent 2–4 cell embryo arrest and diminished apoptosis frequencies after oxidant treatment. The results of this study demonstrate that p66Shc controls the oxidative stress response in early mammalian embryos. Small molecule inhibition of p66Shc may be a viable clinical therapy to increase the developmental potential of in vitro produced mammalian embryos.

As COVID-19 vaccinations became available and were proven effective in preventing serious infection, uptake amongst individuals varied, including in medically vulnerable populations. This cross-sectional multi-site study examined vaccine uptake, hesitancy, and explanatory factors amongst people with serious and/or chronic health conditions, including the impact of underlying disease on attitudes to vaccination. A 42-item survey was distributed to people with cancer, diabetes, or multiple sclerosis across ten Australian health services from 30 June to 5 October 2021. The survey evaluated sociodemographic and disease-related characteristics and incorporated three validated scales measuring vaccine hesitancy and vaccine-related beliefs generally and specific to their disease: the Oxford COVID-19 Vaccine Hesitancy Scale, the Oxford COVID-19 Vaccine Confidence and Complacency Scale and the Disease Influenced Vaccine Acceptance Scale-Six. Among 4683 participants (2548 [54.4%] female, 2108 [45.0%] male, 27 [0.6%] other; mean [SD] age, 60.6 [13.3] years; 3560 [76.0%] cancer, 842 [18.0%] diabetes, and 281 [6.0%] multiple sclerosis), 3813 (81.5%) self-reported having at least one COVID-19 vaccine. Unvaccinated status was associated with younger age, female sex, lower education and income, English as a second language, and residence in regional areas. Unvaccinated participants were more likely to report greater vaccine hesitancy and more negative perceptions toward vaccines. Disease-related vaccine concerns were associated with unvaccinated status and hesitancy, including greater complacency about COVID-19 infection, and concerns relating to vaccine efficacy and impact on their disease and/or treatment. This highlights the need to develop targeted strategies and education about COVID-19 vaccination to support medically vulnerable populations and health professionals.

Introduction People with cancer are at higher risk of serious illness and death from COVID‐19 infection. We investigated COVID‐19 vaccine uptake among patients with solid organ and blood cancers and explored factors related to hesitancy. Methods Cross‐sectional online survey of adults with a history of cancer at three health services across metropolitan and regional Victoria. Vaccine hesitancy was measured by the validated Oxford COVID‐19 vaccine hesitancy scale. Results There were 1073 respondents: 56% female; median age 62 years (range 23 ‐ 91). Commonest tumor types included breast 29%, gastrointestinal 19%, hematological 15%, genitourinary 15%, and lung 8%. Thirty‐six percent had metastatic disease, and 54% were receiving active anticancer treatment. Eighty‐four percent of respondents indicated positive intent toward COVID‐19 vaccination, 10% were undecided, and 6% indicated negative attitudes. At least one vaccine dose had been received by 65% of respondents, leaving 35% unvaccinated. Fifty‐eight percent of unvaccinated patients answered that they would “definitely” or “probably” take a vaccine. Higher vaccine uptake was significantly associated with older age, male gender, English as first language, longer time since cancer diagnosis, and not being on current anticancer treatment. Concerns regarding vaccine side effects, particularly thrombosis, and the desire for clear medical advice were prominent among unvaccinated respondents. Conclusion Despite being eligible for COVID‐19 vaccination since March 2021, a substantial minority of patients with cancer remained unvaccinated as of August 2021. Targeted communication and educational resources addressing vaccine safety in the context of cancer are key to promoting vaccine uptake in this vulnerable population.

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