mRNA-Based Vaccines Are Highly Immunogenic and Confer Protection in the Gnotobiotic Pig Model of Human Rotavirus Diarrhea.

Human rotavirus (HRV) is still a leading cause of severe dehydrating gastroenteritis globally, particularly in infants and children. Previously, we demonstrated the immunogenicity of mRNA-based HRV vaccine candidates expressing the viral spike protein VP8* in rodent models. In the present study, we assessed the immunogenicity and protective efficacy of two mRNA-based HRV trivalent vaccine candidates, encoding VP8* of the genotypes P[8], P[6], or P[4], in the gnotobiotic (Gn) pig model of Wa (G1P[8]) HRV infection and diarrhea. Vaccines either encoded VP8* alone fused to the universal T-cell epitope P2 (P2-VP8*) or expressed P2-VP8* as a fusion protein with lumazine synthase (LS-P2-VP8*) to allow the formation and secretion of protein particles that present VP8* on their surface. Gn pigs were randomly assigned into groups and immunized three times with either P2-VP8* (30 µg) or LS-P2-VP8* (30 µg or 12 µg). A trivalent alum-adjuvanted P2-VP8* protein vaccine or an LNP-formulated irrelevant mRNA vaccine served as the positive and negative control, respectively. Upon challenge with virulent Wa HRV, a significantly shortened duration and decreased severity of diarrhea and significant protection from virus shedding was induced by both mRNA vaccine candidates compared to the negative control. Both LS-P2-VP8* doses induced significantly higher VP8*-specific IgG antibody titers in the serum after immunizations than the negative as well as the protein control. The P[8] VP8*-specific IgG antibody-secreting cells in the ileum, spleen, and blood seven days post-challenge, as well as VP8*-specific IFN-γ-producing T-cell numbers increased in all three mRNA-vaccinated pig groups compared to the negative control. Overall, there was a clear tendency towards improved responses in LS-P2-VP8* compared to the P2-VP8*mRNA vaccine. The demonstrated strong humoral immune responses, priming for effector T cells, and the significant reduction of viral shedding and duration of diarrhea in Gn pigs provide a promising proof of concept and may provide guidance for the further development of mRNA-based rotavirus vaccines.

Shifting threat criterion for morphed facial expressions reduces negative affect.

It is well-established that anxiety and/or depression are associated with a negative bias when interpreting ambiguous information. This study tested the novel hypothesis that the criterion one sets for judging a stimulus as threatening is a core aspect of this bias. A sample of 174 participants were divided into neutral (n = 87) and threatening (n = 87) training conditions. Participants performed a facial expression detection task, in which criterion was shifted in the liberal (threatening condition) or conservative (neutral condition) direction via differential reward contingencies. Training conditions were successful in inducing large shifts in criterion as intended. There was also a small change in sensitivity in the neutral condition, however, the manipulation is still considered successful given the substantive effect size for change in criterion compared to change in sensitivity. As predicted, conservative criterion-training resulted in significantly lower levels of negative affect post-training. No significant change was found for liberal criterion-training on negative affect. Positive affect also decreased across time regardless of condition. Overall, the reduction in negative affect following conservative criterion-training demonstrates that modifying criterion impacts affect and identifies criterion setting as a potential target in the treatment of mental health disorders with prominent negative affect.

Health and Lifestyle Factors of Australian Medical Radiation Workers: A Pilot Study Using Nuclear Medicine Technologists.

The health effects of chronic low-dose radiation exposure are a subject of worldwide debate. These effects are difficult to assess because all low-dose exposure mechanisms must be accounted for, including background exposure, personal medical examinations, and environmental exposure such as aviation, as well as lifestyle choices contributing to disease. The current literature recommends investigation of lifestyle factors to fill in these gaps. The aim of this study was to pilot-test a survey developed to assess health and lifestyle factors for Australian medical radiation workers. Methods: A cohort of nuclear medicine technologists (NMTs) was selected to test the survey. The survey consisted of 53 questions relating to demographics, employment, lifestyle, and health. Data from the 2017-2018 Australian National Health Survey were used to compare the lifestyle choices and health of the participants with those of the Australian general population. Results: In total, 101 participants pilot-tested the survey. Overall, Australian NMTs make better lifestyle choices (more exercise, more vegetable intake, lower rates of smoking and alcohol consumption) resulting in lower rates of obesity than the Australian general population. NMTs had a higher reported health status than the Australian population, with lower levels of psychologic distress. Given the low age of NMTs participating in the study, the cancer incidence rate may be higher than that reported for the Australian general population; however, a larger sample size is required to provide more definitive results. Conclusion: This pilot study demonstrated the feasibility of conducting a widespread survey to assess health and lifestyle factors for the Australian medical radiation worker cohort. Comparison of survey results with data for the entire Australian population have highlighted the potential to increase the number of lifestyle questions.