Continuous Flow Biocatalytic Reductive Amination by Co-Entrapping Dehydrogenases with Agarose Gel in a 3D-Printed Mould Reactor

Herein, we show how the merge of biocatalysis with flow chemistry aided by 3D-printing technologies can facilitate organic synthesis. This concept was exemplified for the reductive amination of benzaldehyde catalysed by co-immobilised amine dehydrogenase and formate dehydrogenase in a continuous flow micro-reactor. For this purpose, we investigated enzyme co-immobilisation by covalent binding, or ion-affinity binding, or entrapment. Entrapment in an agarose hydrogel turned out to be the most promising solution for this biocatalytic reaction. Therefore, we developed a scalable and customisable approach whereby an agarose hydrogel containing the co-entrapped dehydrogenases was cast in a 3D-printed mould. The reactor was applied to the reductive amination of benzaldehyde in continuous flow over 120 h and afforded 47 % analytical yield and a space-time yield of 7.4 g L day−1 using 0.03 mol% biocatalysts loading. This work also exemplifies how rapid prototyping of enzymatic reactions in flow can be achieved through 3D-printing technology

Cross-cohort change in parent-reported emotional problem trajectories across childhood and adolescence in the UK

Background Over the past three decades, the prevalence of adolescent emotional problems (ie, anxiety and depression) has risen. Although the onset and developmental course of emotional symptoms shows high variability, no study has directly tested secular differences across development. Our aim was to investigate whether and how developmental trajectories of emotional problems have changed across generations. Methods We used data from two UK prospective cohorts assessed 10 years apart: the Avon Longitudinal Study of Parents and Children (ALSPAC) including individuals born in 1991–92, and the Millennium Cohort Study (MCS) with individuals born in 2000–02. Our outcome was emotional problems, assessed using the parent-rated emotional subscale of the Strengths and Difficulties Questionnaire (SDQ-E) at approximate ages 4, 7, 8, 10, 11, 13, and 17 years in ALSPAC and ages 3, 5, 7, 11, 14, and 17 years in MCS. Participants were included if the SDQ-E was completed at least once in childhood and at least once in adolescence. Trajectories were generated using multilevel growth curve models using the repeated assessments of the SDQ-E in children aged 3–17 years. Findings Data were available for 19 418 participants (7012 from ALSPAC and 12 406 from the MCS), of whom 9678 (49·8%) were female and 9740 (50·2%) were male, and 17 572 (90·5%) had White mothers. Individuals born between 2000 and 2002 had higher emotional problem scores from around 9 years (intercept statistic β 1·75, 95% CI 1·71–1·79) than did individuals born in 1991–92 (1·55, 1·51–1·59). The later cohort had an earlier onset of problems than the earlier cohort, and sustained higher average trajectories from around 11 years, with female adolescents showing the steepest trajectories of emotional problems. Differences between cohorts peaked overall at age 14 years. Interpretation Our comparison of two cohorts of young people provides evidence that compared with a cohort assessed 10 years prior, emotional problems emerge earlier in development in the more recent cohort, and these are especially pronounced for females during mid-adolescence. Such findings have implications for public health planning and service provision

Cellular Postconditioning: Allogeneic Cardiosphere-Derived Cells Reduce Infarct Size and Attenuate Microvascular Obstruction When Administered After Reperfusion in Pigs With Acute Myocardial Infarction

Intracoronary (IC) delivery of cardiosphere-derived cells (CDCs) has been demonstrated to be safe and effective in porcine and human chronic myocardial infarction (MI). However, IC delivery of CDCs after reperfusion in acute MI has never been assessed in a clinically-relevant large animal model. We tested CDCs as adjunctive therapy to reperfusion in a porcine model of MI

Allogeneic Cardiospheres Delivered via Percutaneous Transendocardial Injection Increase Viable Myocardium, Decrease Scar Size, and Attenuate Cardiac Dilatation in Porcine Ischemic Cardiomyopathy

BackgroundEpicardial injection of heart-derived cell products is safe and effective post-myocardial infarction (MI), but clinically-translatable transendocardial injection has never been evaluated. We sought to assess the feasibility, safety and efficacy of percutaneous transendocardial injection of heart-derived cells in porcine chronic ischemic cardiomyopathy.Methods and ResultsWe studied a total of 89 minipigs; 63 completed the specified protocols. After NOGA-guided transendocardial injection, we quantified engraftment of escalating doses of allogeneic cardiospheres or cardiosphere-derived cells in minipigs (n = 22) post-MI. Next, a dose-ranging, blinded, randomized, placebo-controlled (“dose optimization”) study of transendocardial injection of the better-engrafting product was performed in infarcted minipigs (n = 16). Finally, the superior product and dose (150 million cardiospheres) were tested in a blinded, randomized, placebo-controlled (“pivotal”) study (n = 22). Contrast-enhanced cardiac MRI revealed that all cardiosphere doses preserved systolic function and attenuated remodeling. The maximum feasible dose (150 million cells) was most effective in reducing scar size, increasing viable myocardium and improving ejection fraction. In the pivotal study, eight weeks post-injection, histopathology demonstrated no excess inflammation, and no myocyte hypertrophy, in treated minipigs versus controls. No alloreactive donor-specific antibodies developed over time. MRI showed reduced scar size, increased viable mass, and attenuation of cardiac dilatation with no effect on ejection fraction in the treated group compared to placebo.ConclusionsDose-optimized injection of allogeneic cardiospheres is safe, decreases scar size, increases viable myocardium, and attenuates cardiac dilatation in porcine chronic ischemic cardiomyopathy. The decreases in scar size, mirrored by increases in viable myocardium, are consistent with therapeutic regeneration

Pandemic Boredom: Little Evidence That Lockdown-Related Boredom Affects Risky Public Health Behaviors Across 116 Countries

Some public officials have expressed concern that policies mandating collective public health behaviors (e.g., national/regional "lockdown ") may result in behavioral fatigue that ultimately renders such policies ineffective. Boredom, specifically, has been singled out as one potential risk factor for noncompliance. We examined whether there was empirical evidence to support this concern during the COVID-19 pandemic in a large cross-national sample of 63,336 community respondents from 116 countries. Although boredom was higher in countries with more COVID-19 cases and in countries that instituted more stringent lockdowns, such boredom did not predict longitudinal within-person decreases in social distancing behavior (or vice versa; n = 8,031) in early spring and summer of 2020. Overall, we found little evidence that changes in boredom predict individual public health behaviors (handwashing, staying home, self-quarantining, and avoiding crowds) over time, or that such behaviors had any reliable longitudinal effects on boredom itself. In summary, contrary to concerns, we found little evidence that boredom posed a public health risk during lockdown and quarantine

Concern with COVID-19 pandemic threat and attitudes towards immigrants: The mediating effect of the desire for tightness

Tightening social norms is thought to be adaptive for dealing with collective threat yet it may have negative consequences for increasing prejudice. The present research investigated the role of desire for cultural tightness, triggered by the COVID-19 pandemic, in increasing negative attitudes towards immigrants. We used participant-level data from 41 countries (N = 55,015) collected as part of the PsyCorona project, a crossnational longitudinal study on responses to COVID-19. Our predictions were tested through multilevel and SEM models, treating participants as nested within countries. Results showed that people’s concern with COVID19 threat was related to greater desire for tightness which, in turn, was linked to more negative attitudes towards immigrants. These findings were followed up with a longitudinal model (N = 2,349) which also showed that people’s heightened concern with COVID-19 in an earlier stage of the pandemic was associated with an increase in their desire for tightness and negative attitudes towards immigrants later in time. Our findings offer insight into the trade-offs that tightening social norms under collective threat has for human groups

Trust in government regarding COVID-19 and its associations with preventive health behaviour and prosocial behaviour during the pandemic: a cross-sectional and longitudinal study

Background. The effective implementation of government policies and measures for controlling the coronavirus disease 2019 (COVID-19) pandemic requires compliance from the public. This study aimed to examine cross-sectional and longitudinal associations of trust ingovernment regarding COVID-19 control with the adoption of recommended health behaviours and prosocial behaviours, and potential determinants of trust in government duringthe pandemic.Methods. This study analysed data from the PsyCorona Survey, an international project onCOVID-19 that included 23 733 participants from 23 countries (representative in age andgender distributions by country) at baseline survey and 7785 participants who also completedfollow-up surveys. Specification curve analysis was used to examine concurrent associationsbetween trust in government and self-reported behaviours. We further used structural equation model to explore potential determinants of trust in government. Multilevel linear regressions were used to examine associations between baseline trust and longitudinal behavioural changes.Results. Higher trust in government regarding COVID-19 control was significantly associatedwith higher adoption of health behaviours (handwashing, avoiding crowded space, self-quarantine) and prosocial behaviours in specification curve analyses (median standardised β =0.173 and 0.229, p < 0.001). Government perceived as well organised, disseminating clear messages and knowledge on COVID-19, and perceived fairness were positively associated withtrust in government (standardised β = 0.358, 0.230, 0.056, and 0.249, p < 0.01). Higher trustat baseline survey was significantly associated with lower rate of decline in health behavioursover time ( p for interaction = 0.001).Conclusions. These results highlighted the importance of trust in government in the control of Covid-19

.Using machine learning to identify important predictors of COVID-19 infection prevention behaviors during the early phase of the pandemic

Before vaccines for coronavirus disease 2019 (COVID-19) became available, a set of infection-prevention behaviors constituted the primary means to mitigate the virus spread. Our study aimed to identify important predictors of this set of behaviors. Whereas social and health psychological theories suggest a limited set of predictors, machine-learning analyses can identify correlates from a larger pool of candidate predictors. We used random forests to rank 115 candidate correlates of infection-prevention behavior in 56,072 participants across 28 countries, administered in March to May 2020. The machine-learning model predicted 52% of the variance in infection-prevention behavior in a separate test sample—exceeding the performance of psychological models of health behavior. Results indicated the two most important predictors related to individuallevel injunctive norms. Illustrating how data-driven methods can complement theory, some of the most important predictors were not derived from theories of health behavior—and some theoretically derived predictors were relatively unimportant

‘We are all in the same boat’ : how societal discontent affects intention to help during the COVID-19 pandemic

The coronavirus disease 2019 (COVID-19) pandemic has caused a global health crisis. Consequently, many countries have adopted restrictive measures that caused a substantial change in society. Within this framework, it is reasonable to suppose that a sentiment of societal discontent, defined as generalized concern about the precarious state of society, has arisen. Literature shows that collectively experienced situations can motivate people to help each other. Since societal discontent is conceptualized as a collective phenomenon, we argue that it could influence intention to help others, particularly those who suffer from coronavirus. Thus, in the present study, we aimed (a) to explore the relationship between societal discontent and intention to help at the individual level and (b) to investigate a possible moderating effect of societal discontent at the country level on this relationship. To fulfil our purposes, we used data collected in 42 countries (N = 61,734) from the PsyCorona Survey, a cross-national longitudinal study. Results of multilevel analysis showed that, when societal discontent is experienced by the entire community, individuals dissatisfied with society are more prone to help others. Testing the model with longitudinal data (N = 3,817) confirmed our results. Implications for those findings are discussed in relation to crisis management. Please refer to the Supplementary Material section to find this article's Community and Social Impact Statement