Psychological and psychosocial determinants of COVID related face covering behaviours: A systematic review.

Background: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has resulted in illness, deaths and societal disruption on a global scale. Societies have implemented various control measures to reduce transmission of the virus and mitigate its impact. Individual behavioural changes are crucial to the successful implementation of these measures. One commonly recommended measure to limit risk of infection is face covering. It is important to identify those factors that can predict the uptake and maintenance of face covering. Objectives: We aimed to identify and synthesise the evidence on malleable psychological and psychosocial factors that determine uptake and adherence to face covering aimed at reducing the risk of infection or transmission of COVID-19. Search Methods: We searched various literature sources including electronic databases (Medline ALL, Child Development & Adolescent Studies, ERIC, PsycInfo, CINAHL & Web of Science), web searches, conference proceedings, government reports, other repositories of literature and grey literature. The search strategy was built around three concepts of interest including (1) context (terms relating to COVID19), (2) behaviour of interest and (3) terms related to psychological and psychosocial determinants of COVID Health-Related Behaviours and adherence or compliance with face covering, to capture malleable determines. Searches capture studies up until October 2021. Selection Criteria: Eligibility criteria included observational studies (both retrospective and prospective) and experimental studies that measure and report malleable psychological and psychosocial determinants and handwashing at an individual level, amongst the general public. Screening was supported by the Cochrane Crowd. Studies titles and abstracts were screened against the eligibility criteria by three independent screeners. Following this, all potentially relevant studies were screened at full-text level by the research team. All conflicts between screeners were resolved by discussion between the core research team. Data Collection and Analysis: All data extraction was managed in EPPI-Reviewer software. All eligible studies, identified through full-text screening were extracted by one author. We extracted data on study information, population, determinant, behaviour and effects. A second author checked data extraction on 20% of all included papers. All conflicts were discussed by the two authors until consensus was reached. We assessed methodological quality of all included studies using an adapted version of the Joanna Briggs Institute Quality appraisal tool for cross-sectional studies. Main Results: Our initial searches yielded 23,587 results, of which 23 were included in this review. The included studies were cross-sectional in design, came from nine countries and had a combined sample of 54,401 participants. The vast majority of studies had samples from the general public, with five of the studies focusing on specific samples. All included studies considered people over the age of 18. The quality of 10 of the studies was rated as unclear, 10 were rated as low, and 3 rated high risk of bias, predominately due to lack of reporting of recruitment, sample characteristics and methodology. Ten studies were included in the meta-analysis and 16 in the narrative synthesis. Findings from the meta-analysis indicated that knowledge of COVID-19 (0.341, 95% confidence interval [CI] = 0.06, 0.530, I 2 = 100%) was the malleable determinant most associated with face covering behaviour. Perceived susceptibility of COVID-19 (r = 0.088, 95% CI = -0.004, 0.180, I 2 = 80%) and COVID-related worry and anxiety (r = 0.064, 95% CI = -0.066, 0.191, I 2 = 93% had little to no effect on face covering behaviour. In the narrative synthesis, the strongest association was found between perceived benefits and effectiveness of behaviours and mask wearing behaviour. Authors' Conclusions: Understanding the effects of various malleable determinants on COVID-related face covering can aid in the development and implementation of interventions and public health campaigns to promote face covering behaviour in potential new waves of COVID-19 or other respiratory infections. Knowledge of COVID and perceived benefits of face coverings warrant further consideration in future research and policy.

Psychological and psychosocial determinants of COVID-related handwashing behaviours: A systematic review.

Background: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has resulted in illness, deaths and societal disruption on a global scale. Societies have implemented various control measures to reduce transmission of the virus and mitigate its impact. Individual behavioural changes are crucial to the successful implementation of these measures. One commonly recommended measure to limit risk of infection is frequent handwashing. It is important to identify those factors that can predict the uptake and maintenance of handwashing. Objectives: We aimed to identify and synthesise the evidence on malleable psychological and psychosocial factors that determine uptake and adherence to handwashing aimed at reducing the risk of infection or transmission of COVID-19. Search Methods: We searched various literature sources including electronic databases (Medline ALL, Child Development & Adolescent Studies, ERIC, PsycInfo, CINAHL and Web of Science), web searches, conference proceedings, government reports, other repositories of literature and grey literature. The search strategy was built around three concepts of interest including (1) context (terms relating to COVID-19), (2) behaviour of interest and (3) terms related to psychological and psychosocial determinants of COVID Health-Related Behaviours and adherence or compliance with handwashing, to capture malleable determines. Searches capture studies up until October 2021. Selection Criteria: Eligibility criteria included observational studies (both retrospective and prospective) and experimental studies that measure and report malleable psychological and psychosocial determinants and handwashing at an individual level, amongst the general public. Screening was supported by the Cochrane Crowd. Titles and abstracts were screened against the eligibility criteria by three independent screeners. Following this, all potentially relevant studies were screened at full-text level by the research team. All conflicts between screeners were resolved by discussion between the core research team. Data Collection and Analysis: All data extraction was managed in EPPI-Reviewer software. All eligible studies, identified through full-text screening were extracted by one author. We extracted data on study information, population, determinant, behaviour and effects. A second author checked data extraction on 20% of all included papers. All conflicts were discussed by the two authors until consensus was reached.We assessed methodological quality of all included studies using an adapted version of the Joanna Briggs Institute Quality appraisal tool for cross-sectional studies. Main Results: Our initial searches yielded 23,587 results, of which 56 studies were included in this review. The included studies were cross sectional in design, came from 22 countries and had a combined sample of 199,376 participants. The vast majority of studies had samples from the general public, with eight of the studies focusing on specific samples. All included studies considered people over the age of 18. The quality of the majority of the studies was good (n = 30 rated low risk of bias), with 8 rated high risk of bias, predominately due to lack of reporting of recruitment, sample characteristics and methodology. Thirty-four studies were included in the narrative synthesis and 28 in the meta-analysis.Findings indicated that emotions about COVID-19 (worry [0.381, confidence interval [CI] = 0.270-0.482, I 2 = 92%) and anxiety (0.308, CI = 0.154-0.448, I 2 = 91%]), knowledge of COVID-19 (0.323, CI = 0.223-0.417, I 2 = 94%), and perceived social norms (0.303, CI = 0.184-0.413, I 2 = 92%) were among the malleable determinants most associated with handwashing. Perceived severity (0.006, CI = -0.011-0.023) and susceptibility of COVID-19 (0.041, CI = -0.034 to 0.115) had little to no effect on handwashing behaviour. Authors' Conclusions: Understanding the effects of various malleable determinants on COVID-related handwashing can aid in the development and implementation of interventions and public health campaigns to promote handwashing behaviour in potential new waves of COVID-19 or other respiratory infections. Emotions about COVID, knowledge of COVID and perceived social norms warrant further consideration in future research and policy.

Single nuclei RNA-seq reveals a medium spiny neuron glutamate excitotoxicity signature prior to the onset of neuronal death in an ovine Huntington's disease model.

Huntington's disease (HD) is a neurodegenerative genetic disorder caused by an expansion in the CAG repeat tract of the huntingtin (HTT) gene resulting in behavioural, cognitive, and motor defects. Current knowledge of disease pathogenesis remains incomplete, and no disease course-modifying interventions are in clinical use. We have previously reported the development and characterisation of the OVT73 transgenic sheep model of HD. The 73 polyglutamine repeat is somatically stable and therefore likely captures a prodromal phase of the disease with an absence of motor symptomatology even at 5-years of age and no detectable striatal cell loss. To better understand the disease-initiating events we have undertaken a single nuclei transcriptome study of the striatum of an extensively studied cohort of 5-year-old OVT73 HD sheep and age matched wild-type controls. We have identified transcriptional upregulation of genes encoding N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors in medium spiny neurons, the cell type preferentially lost early in HD. Further, we observed an upregulation of astrocytic glutamate uptake transporters and medium spiny neuron GABAA receptors, which may maintain glutamate homeostasis. Taken together, these observations support the glutamate excitotoxicity hypothesis as an early neurodegeneration cascade-initiating process but the threshold of toxicity may be regulated by several protective mechanisms. Addressing this biochemical defect early may prevent neuronal loss and avoid the more complex secondary consequences precipitated by cell death.

Proof of concept for multiplex amplicon sequencing for mutation identification using the MinION nanopore sequencer.

Rapid, cost-effective identification of genetic variants in small candidate genomic regions remains a challenge, particularly for less well equipped or lower throughput laboratories. The application of Oxford Nanopore Technologies' MinION sequencer has the potential to fulfil this requirement. We demonstrate a proof of concept for a multiplexing assay that pools PCR amplicons for MinION sequencing to enable sequencing of multiple templates from multiple individuals, which could be applied to gene-targeted diagnostics. A combined strategy of barcoding and sample pooling was developed for simultaneous multiplex MinION sequencing of 100 PCR amplicons. The amplicons are family-specific, spanning a total of 30 loci in DNA isolated from 82 human neurodevelopmental cases and family members. The target regions were chosen for further interrogation because a potentially disease-causative variant had been identified in affected individuals following Illumina exome sequencing. The pooled MinION sequences were deconvoluted by aligning to custom references using the minimap2 aligner software. Our multiplexing approach produced an interpretable and expected sequence from 29 of the 30 targeted genetic loci. The sequence variant which was not correctly resolved in the MinION sequence was adjacent to a five nucleotide homopolymer. It is already known that homopolymers present a resolution problem with the MinION approach. Interestingly despite equimolar quantities of PCR amplicon pooled for sequencing, significant variation in the depth of coverage (127×-19,626×; mean = 8321×, std err = 452.99) was observed. We observed independent relationships between depth of coverage and target length, and depth of coverage and GC content. These relationships demonstrate biases of the MinION sequencer for longer templates and those with lower GC content. We demonstrate an efficient approach for variant discovery or confirmation from short DNA templates using the MinION sequencing device. With less than 130 × depth of coverage required for accurate genotyping, the methodology described here allows for rapid highly multiplexed targeted sequencing of large numbers of samples in a minimally equipped laboratory with a potential cost as much 200 × less than that from Sanger sequencing.

Widespread cis-regulation of RNA editing in a large mammal.

Post-transcriptional RNA editing may regulate transcript expression and diversity in cells, with potential impacts on various aspects of physiology and environmental adaptation. A small number of recent genome-wide studies in Drosophila, mouse, and human have shown that RNA editing can be genetically modulated, highlighting loci that quantitatively impact editing of transcripts. The potential gene expression and physiological consequences of these RNA-editing quantitative trait loci (edQTL), however, are almost entirely unknown. Here, we present analyses of RNA editing in a large domestic mammal (Bos taurus), where we use whole-genome and high-depth RNA sequencing to discover, characterize, and conduct genetic mapping studies of novel transcript edits. Using a discovery population of nine deeply sequenced cows, we identify 2413 edit sites in the mammary transcriptome, the majority of which are adenosine to inosine edits (98.6%). Most sites are predicted to reside in double-stranded secondary structures (85.1%), and quantification of the rates of editing in an additional 355 cows reveals editing is negatively correlated with gene expression in the majority of cases. Genetic analyses of RNA editing and gene expression highlight 152 cis-regulated edQTL, of which 15 appear to cosegregate with expression QTL effects. Trait association analyses in a separate population of 9989 lactating cows also shows 12 of the cis-edQTL coincide with at least one cosegregating lactation QTL. Together, these results enhance our understanding of RNA-editing dynamics in mammals, and suggest mechanistic links by which loci may impact phenotype through RNA editing mediated processes.

Phase I trial of antigen-targeted autologous dendritic cell-based vaccine with in vivo activation of inducible CD40 for advanced prostate cancer.

This phase I trial reports the safety and activity of BPX101, a second-generation antigen-targeted autologous antigen presenting cell (APC) vaccine in men with metastatic castration-resistant prostate cancer (mCRPC). To manufacture BPX101, APCs collected in a single leukapheresis were transduced with adenoviral vector Ad5f35 encoding inducible human (ih)-CD40, followed by incubation with protein PA001, which contains the extracellular domain of human prostate-specific membrane antigen. The ih-CD40 represents a modified chimeric version of the dendritic cell (DC) co-stimulatory molecule, CD40, which responds to a bioinert membrane-permeable activating dimerizer drug, rimiducid (AP1903), permitting temporally controlled, lymphoid-localized, DC-specific activation. Eighteen men with progressive mCRPC following ≤1 prior chemotherapy regimen were enrolled to evaluate three doses of BPX101 (4 × 106, 12.5 × 106 and 25 × 106 cells) administered intradermally every 2-4 weeks followed by rimiducid (0.4 mg/kg) intravenous (IV) infusion 24 h after each BPX101 dose. There were no dose-limiting toxicities. Immune upregulation as well as anti-tumor activity was observed with PSA declines, objective tumor regressions and robust efficacy of post-trial therapy. This novel antigen-targeted and in vivo activated immunotherapy platform may warrant further development as monotherapy and as a component of rational combinations.