Learning from the past? : how biased memories of the pandemic endanger preparation for future crises

As the world transitions to a postpandemic phase, societies are looking to evaluate their past responses to COVID-19 and prepare for future crises. However, a recently published series of studies1 sheds light on a concerning issue; sustained societal polarisation between the vaccinated and unvaccinated is distorting the accuracy of people's recall of the pandemic, fuelling societal conflict and complicating preparation for future pandemics. Here, we summarise the key findings and elaborate on the implications for clinical practice

The moderating role of trust in pandemic-relevant institutions on the relation between pandemic fatigue and vaccination intentions

This research helps to clarify the relation between pandemic fatigue (PF) and vaccination intentions (VI). Theoretically, two patterns seem plausible. First, as with any other health protective measure, PF might reduce the motivation to get vaccinated. Second, PF might increase the motivation to get vaccinated because vaccination reduces the number of (other) health protective measure needed. We tested these two opposing predictions and further explored the moderating role of trust in pandemic-relevant institutions on the link between PF and VI in two large-scale survey studies from Denmark and Germany (collected between 2020 and 2021; total N > 22,000). Data was analyzed using multiple regression models. Analyses reveal a negative link between PF and VI that is less pronounced for people high in trust. Results remain stable when accounting for covariates and quadratic trends. Thus, trust might buffer the negative relation between PF and VI

Measuring the 7Cs of Vaccination Readiness

Abstract. Although vaccines are among the most effective interventions used in fighting diseases, vaccination readiness varies substantially among individuals. Vaccination readiness is defined as a set of components that increase or decrease AN individual’s likelihood of getting vaccinated. Building on earlier work that distinguished five components of vaccination readiness (confidence, complacency, constraints, calculation, and collective responsibility), we revised the questionnaire used to measure these components to improve its psychometric properties, specifically criterion validity. In doing so, we also developed two new components of vaccination readiness: compliance and conspiracy. Compliance is the tendency to support monitoring to control adherence to regulations; conspiracy is the tendency to endorse conspiratorial beliefs about vaccination. The newly introduced 7C scale was initially piloted in a cascade of serial cross-sectional studies and then validated with N = 681 participants from the COVID-19 Snapshot Monitoring in Denmark. We report a bifactor measurement model, convergent validity with other questionnaires, and an explanation of 85% variance in the willingness to vaccinate against COVID-19. We also present a 7-item short version of the scale. The instrument is publicly available in several languages ( www.vaccination-readiness.com ), and we seek collaboration to provide translations of our instrument into other languages

Topographically and chemically enhanced textile polycaprolactone scaffolds for tendon and ligament tissue engineering

The use of tissue engineering to address the shortcomings of current procedures for tendons and ligaments is promising, but it requires a suitable scaffold that meets various mechanical, degradation-related, scalability-related, and biological requirements. Macroporous textile scaffolds made from appropriate fiber material have the potential to fulfill the first three requirements. This study aimed to investigate the biocompatibility, sterilizability, and functionalizability of a multilayer braided scaffold. These macroporous scaffolds with dimensions similar to those of the human anterior cruciate ligament consist of fibers with appropriate tensile strength and degradation behavior melt-spun from Polycaprolactone (PCL). Two different cross-sectional geometries resulting in significantly different specific surface areas and morphologies were used at the fiber level, and a Chitosan-graft-PCL (CS-g-PCL) surface modification was applied to the melt-spun substrates for the first time. All scaffolds elicited a positive cell response, and the CS-g-PCL modification provided a platform for incorporating functionalization agents such as drug delivery systems for growth factors, which were successfully released in therapeutically effective quantities. The fiber geometry was found to be a variable that could be manipulated to control the amount released. Therefore, scaled, surface-modified textile scaffolds are a versatile technology that can successfully address the complex requirements of tissue engineering for ligaments and tendons, as well as other structures

Information nudges for influenza vaccination: Evidence from a large-scale cluster-randomized controlled trial in Finland

Background & nbsp;Vaccination is the most effective means of preventing the spread of infectious diseases. Despite the proven benefits of vaccination, vaccine hesitancy keeps many people from getting vaccinated.& nbsp;Methods and findings & nbsp;We conducted a large-scale cluster randomized controlled trial in Finland to test the effectiveness of centralized written reminders (distributed via mail) on influenza vaccination coverage. The study included the entire older adult population (aged 65 years and above) in 2 culturally and geographically distinct regions with historically low (31.8%, n = 7,398, mean age 75.5 years) and high (57.7%, n = 40,727, mean age 74.0 years) influenza vaccination coverage. The study population was randomized into 3 treatments: (i) no reminder (only in the region with low vaccination coverage); (ii) an individual-benefits reminder, informing recipients about the individual benefits of vaccination; and (iii) an individual- and social-benefits reminder, informing recipients about the additional social benefits of vaccination in the form of herd immunity. There was no control treatment group in the region with high vaccination coverage as general reminders had been sent in previous years. The primary endpoint was a record of influenza vaccination in the Finnish National Vaccination Register during a 5-month follow-up period (from October 18, 2018 to March 18, 2019). Vaccination coverage after the intervention in the region with historically low coverage was 41.8% in the individual-benefits treatment, 38.9% in the individual- and social-benefits treatment and 34.0% in the control treatment group. Vaccination coverage after the intervention in the region with historically high coverage was 59.0% in the individual-benefits treatment and 59.2% in the individual- and social-benefits treatment. The effect of receiving any type of reminder letter in comparison to control treatment group (no reminder) was 6.4 percentage points (95% CI: 3.6 to 9.1, p </p

The Surgical Infection Society revised guidelines on the management of intra-abdominal infection

Background: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations. Methods: Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published since 2008. These publications and additional materials published before 2008 were reviewed by the task force as a whole or by individual subgroups as to relevance to individual questions. Recommendations were developed by a process of iterative consensus, with all task force members voting to accept or reject each recommendation. Grading was based on the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) system; the quality of the evidence was graded as high, moderate, or weak, and the strength of the recommendation was graded as strong or weak. Review of the document was performed by members of the SIS who were not on the task force. After responses were made to all critiques, the document was approved as an official guideline of the SIS by the Executive Council. Results: This guideline summarizes the current recommendations developed by the task force on the treatment of patients who have IAI. Evidence-based recommendations have been made regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy. Additional recommendations related to the treatment of pediatric patients with IAI have been included. Summary: The current recommendations of the SIS regarding the treatment of patients with IAI are provided in this guideline

Structural Basis for a Polθ Helicase Small-Molecule Inhibitor Revealed by Cryo-EM

DNA polymerase theta (Polθ) is a DNA helicase-polymerase protein that facilitates DNA repair and is synthetic lethal with homology-directed repair (HDR) factors. Thus, Polθ is a promising precision oncology drug-target in HDR-deficient cancers. Here, we characterize the binding and mechanism of action of a Polθ helicase (Polθ-hel) small-molecule inhibitor (AB25583) using cryo-EM. AB25583 exhibits 6 nM IC50 against Polθ-hel, selectively kills BRCA1/2-deficient cells, and acts synergistically with olaparib in cancer cells harboring pathogenic BRCA1/2 mutations. Cryo-EM uncovers predominantly dimeric Polθ-hel:AB25583 complex structures at 3.0-3.2 Å. The structures reveal a binding-pocket deep inside the helicase central-channel, which underscores the high specificity and potency of AB25583. The cryo-EM structures in conjunction with biochemical data indicate that AB25583 inhibits the ATPase activity of Polθ-hel helicase via an allosteric mechanism. These detailed structural data and insights about AB25583 inhibition pave the way for accelerating drug development targeting Polθ-hel in HDR-deficient cancers

Discovery of a Small-Molecule Inhibitor that Traps Polθ on DNA and Synergizes with PARP Inhibitors

The DNA damage response (DDR) protein DNA Polymerase θ (Polθ) is synthetic lethal with homologous recombination (HR) factors and is therefore a promising drug target in BRCA1/2 mutant cancers. We discover an allosteric Polθ inhibitor (Polθi) class with 4-6 nM IC50 that selectively kills HR-deficient cells and acts synergistically with PARP inhibitors (PARPi) in multiple genetic backgrounds. X-ray crystallography and biochemistry reveal that Polθi selectively inhibits Polθ polymerase (Polθ-pol) in the closed conformation on B-form DNA/DNA via an induced fit mechanism. In contrast, Polθi fails to inhibit Polθ-pol catalytic activity on A-form DNA/RNA in which the enzyme binds in the open configuration. Remarkably, Polθi binding to the Polθ-pol:DNA/DNA closed complex traps the polymerase on DNA for more than forty minutes which elucidates the inhibitory mechanism of action. These data reveal a unique small-molecule DNA polymerase:DNA trapping mechanism that induces synthetic lethality in HR-deficient cells and potentiates the activity of PARPi