Avian Pathogenic Escherichia coli (APEC) Strain-Dependent Immunomodulation of Respiratory Granulocytes and Mononuclear Phagocytes in CSF1R-Reporter Transgenic Chickens

Avian pathogenic Escherichia coli (APEC) cause severe respiratory and systemic disease in chickens, commonly termed colibacillosis. Early immune responses after initial infection are highly important for the outcome of the infection. In this study, the early interactions between GFP-expressing APEC strains of serotypes O1:K1:H7 and O2:K1:H5 and phagocytic cells in the lung of CSF1R-reporter transgenic chickens were investigated. CSF1R-reporter transgenic chickens express fluorescent protein under the control of elements of the CSF1R promoter and enhancer, such that cells of the myeloid lineage can be visualized in situ and sorted. Chickens were separately inoculated with APEC strains expressing GFP and culled 6 h post-infection. Flow cytometric analysis was performed to phenotype and sort the cells that harbored bacteria in the lung, and the response of the sorted cells was defined by transcriptomic analysis. Both APEC strains were mainly detected in CSF1R-transgeneneg (CSF1R-tgneg) and CSF1R-tglow MHC IIneg MRC1L-Bneg cells and low numbers of APEC were detected in CSF1R-tghigh MHC IIpos MRC1L-Bpos cells. Transcriptomic and flow cytometric analysis identified the APECpos CSF1R-tgneg and CSF1R-tglow cells as heterophils and the APECpos CSF1R-tghigh cells as macrophages and dendritic cells. Both APEC strains induced strong inflammatory responses, however in both CSF1R-tgneg/low and CSF1R-tghigh cells, many immune related pathways were repressed to a greater extent or less activated in birds inoculated with APEC O2-GFP compared to APEC O1-GFP inoculated birds. Comparison of the immune pathways revealed the aryl hydrocarbon receptor (AhR) pathway, IL17 and STAT3 signaling, heterophil recruitment pathways and the acute phase response, are modulated particularly post-APEC O2-GFP inoculation. In contrast to in vivo data, APEC O2-GFP was more invasive in CSF1R-tghigh cells in vitro than APEC O1-GFP and had higher survival rates for up to 6 h post-infection. Our data indicate significant differences in the responses induced by APEC strains of prevalent serotypes, with important implications for the design and interpretation of future studies. Moreover, we show that bacterial invasion and survival in phagocyte populations in vitro is not predictive of events in the chicken lung

31064 The Detroit Keloid Scale: A validated tool for rating keloids

Background: No keloid-specific outcome measures exist. Objective: To develop and validate the Detroit Keloid Scale (DKS), a standardized method of keloid assessment to better compare treatments. Methods: Forty-seven physicians were polled to develop the DKS. The scale was validated in 52 patients with keloids against the Vancouver Scar Scale (VSS), Patient and Observer Scar Assessment Scale (POSAS), and Dermatology Life Quality Index (DLQI) by 3 physicians. Results: The interrater reliability was “substantial” for observer component of the DKS and only “moderate” for the VSS and observer POSAS (ICC were 0.80, 0.60, and 0.47, respectively). Pearson’s correlation indicated a “moderate” association between the observer component of DKS with observer component of POSAS (ρ = 0.56, P \u3c.001) and a “substantial” relationship between the observer component of DKS and VSS (ρ = 0.63, P \u3c.001). Pearson’s correlation indicated a “moderate” association between the patient portion of DKS and patient portion of POSAS and the patient portion of the DKS and DLQI (0.61 and 0.60, respectively, P \u3c.05). The DKS total score consistently showed “substantial” relationship with POSAS total score (ρ = 0.65, P \u3c.001). Limitations: Single center study, no intrarater reliability analysis. Conclusions: The substantial interrater reliability of the DKS will allow for improved standardization in future keloid research

Improving the mental health of farmers: what types of remote support are acceptable, feasible, and improve outcomes? A feasibility RCT

Background: The farming community have high rates of poor mental health, and are relatively ‘hard to reach’ with mental health services. The aim of this study was therefore to undertake a feasibility RCT, based on two mental health interventions. These were (1) CBT based ‘Living Life to the Full for Farming Communities’ (LLTTF-F; www.llttf.com), and (2) a holistic social and emotional support service delivered by the Royal Scottish Agricultural Benevolent Institution (RSABI). The feasibility was supplemented by process evaluation. Methods: This feasibility study aimed to recruit 40 individuals from the farming community who were experiencing a common health problem defined as a score of > = 8 on PHQ-9. A snowball approach was used to recruit interested individuals who had an association with farming. An initial telephone call screened for eligibility and obtained consent to randomisation to the two specified interventions, or to a thirdly group receiving a combination of both LLTTF-F and ‘Social and emotional support’. Participants were permitted to override the randomised option if they expressed a strong preference before the interventions began. Results: Thirty-two participants provided baseline and three-month data. All three interventions showed positive improvements on PHQ-9 scores as follows: the ‘combined intervention’ mean baseline score was 18.1 compared to 12.0 at 3-month follow-up (mean change 6.1). ‘Social and emotional support’ mean baseline score was 11.3 compared to 6.7 at 3-month follow-up (mean change 4.6). ‘LLTTF-F CBT-based intervention only’ mean baseline score was 11.8 compared to 4.5 at 3-month follow-up (mean change 7.3). The retention rate was 81% at three months. In a sub-group of the LLTTF-F CBT-based intervention online materials were supplemented by telephone guided support. This approach received very positive feedback. Conclusions: Recruitment from the farming community required intense effort, and good engagement can then be retained for at least three months. There is evidence that the interventions used were feasible, and tentative evidence that they had a demonstrable effect on mental wellbeing, with the LLTTFF providing the largest effect on PHQ-9 scores. Trial Registration Number ISRCTN27173711, submitted 25/08/2023, confirmed 22/092023

The degree of microbiome complexity influences the epithelial response to infection

<p>Abstract</p> <p>Background</p> <p>The human microflora is known to be extremely complex, yet most pathogenesis research is conducted in mono-species models of infection. Consequently, it remains unclear whether the level of complexity of a host's indigenous flora can affect the virulence potential of pathogenic species. Furthermore, it remains unclear whether the colonization by commensal species affects a host cell's response to pathogenic species beyond the direct physical saturation of surface receptors, the sequestration of nutrients, the modulation of the physico-chemical environment in the oral cavity, or the production of bacteriocins. Using oral epithelial cells as a model, we hypothesized that the virulence of pathogenic species may vary depending on the complexity of the flora that interacts with host cells.</p> <p>Results</p> <p>This is the first report that determines the global epithelial transcriptional response to co-culture with defined complex microbiota. In our model, human immortalized gingival keratinocytes (HIGK) were infected with mono- and mixed cultures of commensal and pathogenic species. The global transcriptional response of infected cells was validated and confirmed phenotypically. In our model, commensal species were able to modulate the expression of host genes with a broad diversity of physiological functions and antagonize the effect of pathogenic species at the cellular level. Unexpectedly, the inhibitory effect of commensal species was <it>not </it>correlated with its ability to inhibit adhesion or invasion by pathogenic species.</p> <p>Conclusion</p> <p>Studying the global transcriptome of epithelial cells to single and complex microbial challenges offers clues towards a better understanding of how bacteria-bacteria interactions and bacteria-host interactions impact the overall host response. This work provides evidence that the degree of complexity of a mixed microbiota <it>does </it>influence the transcriptional response to infection of host epithelial cells, and challenges the current dogma regarding the <it>potential </it>versus the <it>actual </it>pathogenicity of bacterial species. These findings support the concept that members of the commensal oral flora have evolved cellular mechanisms that directly modulate the host cell's response to pathogenic species and dampen their relative pathogenicity.</p

Improving the mental health of farmers: what types of remote support are acceptable, feasible, and improve outcomes? A feasibility RCT

Abstract Background The farming community have high rates of poor mental health, and are relatively ‘hard to reach’ with mental health services. The aim of this study was therefore to undertake a feasibility RCT, based on two mental health interventions. These were (1) CBT based ‘Living Life to the Full for Farming Communities’ (LLTTF-F; www.llttf.com), and (2) a holistic social and emotional support service delivered by the Royal Scottish Agricultural Benevolent Institution (RSABI). The feasibility was supplemented by process evaluation. Methods This feasibility study aimed to recruit 40 individuals from the farming community who were experiencing a common health problem defined as a score of >  = 8 on PHQ-9. A snowball approach was used to recruit interested individuals who had an association with farming. An initial telephone call screened for eligibility and obtained consent to randomisation to the two specified interventions, or to a thirdly group receiving a combination of both LLTTF-F and ‘Social and emotional support’. Participants were permitted to override the randomised option if they expressed a strong preference before the interventions began. Results Thirty-two participants provided baseline and three-month data. All three interventions showed positive improvements on PHQ-9 scores as follows: the ‘combined intervention’ mean baseline score was 18.1 compared to 12.0 at 3-month follow-up (mean change 6.1). ‘Social and emotional support’ mean baseline score was 11.3 compared to 6.7 at 3-month follow-up (mean change 4.6). ‘LLTTF-F CBT-based intervention only’ mean baseline score was 11.8 compared to 4.5 at 3-month follow-up (mean change 7.3). The retention rate was 81% at three months. In a sub-group of the LLTTF-F CBT-based intervention online materials were supplemented by telephone guided support. This approach received very positive feedback. Conclusions Recruitment from the farming community required intense effort, and good engagement can then be retained for at least three months. There is evidence that the interventions used were feasible, and tentative evidence that they had a demonstrable effect on mental wellbeing, with the LLTTFF providing the largest effect on PHQ-9 scores

Improving the mental health of farmers: what types of remote support are acceptable, feasible, and improve outcomes? A feasibility RCT

Abstract Background The farming community have high rates of poor mental health, and are relatively ‘hard to reach’ with mental health services. The aim of this study was therefore to undertake a feasibility RCT, based on two mental health interventions. These were (1) CBT based ‘Living Life to the Full for Farming Communities’ (LLTTF-F; www.llttf.com), and (2) a holistic social and emotional support service delivered by the Royal Scottish Agricultural Benevolent Institution (RSABI). The feasibility was supplemented by process evaluation. Methods This feasibility study aimed to recruit 40 individuals from the farming community who were experiencing a common health problem defined as a score of >  = 8 on PHQ-9. A snowball approach was used to recruit interested individuals who had an association with farming. An initial telephone call screened for eligibility and obtained consent to randomisation to the two specified interventions, or to a thirdly group receiving a combination of both LLTTF-F and ‘Social and emotional support’. Participants were permitted to override the randomised option if they expressed a strong preference before the interventions began. Results Thirty-two participants provided baseline and three-month data. All three interventions showed positive improvements on PHQ-9 scores as follows: the ‘combined intervention’ mean baseline score was 18.1 compared to 12.0 at 3-month follow-up (mean change 6.1). ‘Social and emotional support’ mean baseline score was 11.3 compared to 6.7 at 3-month follow-up (mean change 4.6). ‘LLTTF-F CBT-based intervention only’ mean baseline score was 11.8 compared to 4.5 at 3-month follow-up (mean change 7.3). The retention rate was 81% at three months. In a sub-group of the LLTTF-F CBT-based intervention online materials were supplemented by telephone guided support. This approach received very positive feedback. Conclusions Recruitment from the farming community required intense effort, and good engagement can then be retained for at least three months. There is evidence that the interventions used were feasible, and tentative evidence that they had a demonstrable effect on mental wellbeing, with the LLTTFF providing the largest effect on PHQ-9 scores

Crypto Bestiary: \u3ci\u3eA monstrous manual to the many fraudulent accounts involved in cryptocurrency scams and fraud.\u3c/i\u3e

Cryptocurrencies have fueled the growth of online fraud in various forms. They are poorly understood by many users, have value that shifts quickly and unexpectedly, and are easy to move in a digital world without borders. Cryptocurrency is seemingly purpose built as a tool for hucksters and scammers. The Federal Trade Commission claims that 46,000 people reported losing over a billion dollars in cryptocurrency to scammers in the first six months of 2021,1 a figure only including those potentially few people have been brave enough to share that they have been victims. The world of cryptocurrency can be scary for the uninitiated. One common way in which crypto-fraud is accomplished is through social media and the use of fake accounts. Some accounts purport to be crypto-fans, others make you belive they are experts in crypto-investment and are happy to help you uncover hidden riches. All of them, however, are seeking to take your money and leave you with nothing but fear and regret. This crypto-bestiary will present you, the neophyte, six of the most terrifying of crypto-creatures seeking to steal your treasure. Heed what we tell you as a lesson, be wary of where you venture and watch for the signs

Credibility in Policy Expertise: The Function of Boundaries Between Research and Policy

As science becomes an increasingly crucial resource for addressing complex challenges in society, extensive demands are placed upon the researchers who produce it. Creating valuable expert knowledge that intervenes in policy or practice requires knowledge brokers to facilitate interactions at the boundary between research and policy. Yet, existing research lacks a compelling account of the ways in which brokerage is performed to gain credibility. Drawing on mixed-method analysis of twelve policy research settings, I outline a novel set of strategies for attaining symbolic power, whereby policy experts position themselves and others via conceptual distances drawn between the ‘world of ideas’ and the ‘world of policy and practice’. Disciplinary distance works to situate research as either disciplinary or undisciplinary, epistemic distance creates a boundary between complex specialist research and direct digestible outputs, temporal distance represents the separation of slow rigorous research and agile responsive analysis, and economic distance situates research as either pure and intrinsic or marketable and fundable. I develop a theoretical account that unpacks the boundaries between research communities and shows how these boundaries permit policy research actors to achieve various strategic aims.ESRC Future Research Leaders ES/N016319/1 Commonwealth Scholarship Commissio

The Composite Task Reveals Stronger Holistic Processing in Children than Adults for Child Faces

Background: While own-age faces have been reported to be better recognized than other-age faces, the underlying cause of this phenomenon remains unclear. One potential cause is holistic face processing, a special kind of perceptual and cognitive processing reserved for perceiving upright faces. Previous studies have indeed found that adults show stronger holistic processing when looking at adult faces compared to child faces, but whether a similar own-age bias exists in children remains to be shown. Methodology/Principal Findings: Here we used the composite face task – a standard test of holistic face processing – to investigate if, for child faces, holistic processing is stronger for children than adults. Results showed child participants (8–13 years) had a larger composite effect than adult participants (22–65 years). Conclusions/Significance: Our finding suggests that differences in strength of holistic processing may underlie the ownage bias on recognition memory. We discuss the origin of own-age biases in terms of relative experience, face-space tuning, and social categorization