Inhibition of Marek's Disease Virus Replication and Spread by 25-hydroxycholesterol and 27-hydroxycholesterol In Vitro.

Marek's disease virus (MDV) causes a deadly lymphoproliferative disease in chickens, resulting in huge economic losses in the poultry industry. It has been suggested that MDV suppresses the induction of type I interferons and thus escapes immune control. Cholesterol 25-hydroxylase (CH25H), a gene that encodes an enzyme that catalyses cholesterol to 25-hydroxycholesterol (25-HC), is an interferon-stimulating gene (ISG) known to exert antiviral activities. Other oxysterols, such as 27-hydroxycholesterols (27-HC), have also been shown to exert antiviral activities, and 27-HC is synthesised by the catalysis of cholesterol via the cytochrome P450 enzyme oxidase sterol 27-hydroxylase A1 (CYP27A1). At 24 h post infection (hpi), MDV stimulated a type I interferon (IFN-α) response, which was significantly reduced at 48 and 72 hpi, as detected using the luciferase assay for chicken type I IFNs. Then, using RT-PCR, we demonstrated that chicken type I IFN (IFN-α) upregulates chicken CH25H and CYP27A1 genes in chicken embryo fibroblast (CEF) cells. In parallel, our results demonstrate a moderate and transient upregulation of CH25H at 48 hpi and CYP27A1 at 72hpi in MDV-infected CEF cells. A significant reduction in MDV titer and plaque sizes was observed in CEFs treated with 25-HC or 27-HC in vitro, as demonstrated using a standard plaque assay for MDV. Taken together, our results suggest that 25-HC and 27-HC may be useful antiviral agents to control MDV replication and spread.

Impact of vascular screening interventions on perceived threat, efficacy beliefs and behavioural intentions: a systematic narrative review.

Health-related behaviours contribute to the global burden of cardiovascular disease (CVD). Cardiovascular imaging can be used to screen asymptomatic individuals for increased risk of CVD to enable earlier interventions to promote health-related behaviours to prevent or reduce CVD risk. Some theories of behaviour and behaviour change assume that engagement in a given behaviour is a function of individual threat appraisals, beliefs regarding the performance of behaviour, self-efficacy for performing the desired behaviour and/or dispositions to act (e.g. behavioural intentions). To date, little is known about the impact of cardiovascular imaging interventions on these constructs. This article summarises evidence related to perceived threat, efficacy beliefs, and behavioural intentions after CVD screening. We identified 10 studies (2 RCTs and 8 non-randomised studies, n = 2498) through a combination of screening citations from published systematic reviews and meta-analyses and searching electronic databases. Of these, 7 measured behavioural intentions and perceived susceptibility and 3 measured efficacy beliefs. Findings showed largely encouraging effects of screening interventions on bolstering self-efficacy beliefs and strengthening behavioural intentions. Imaging results that suggest the presence of coronary or carotid artery disease also increased perceived susceptibility to CVD. However, the review also identified some gaps in the literature, such as a lack of guiding theoretical frameworks and assessments of critical determinants of health-related behaviours. By carefully considering the key issues highlighted in this review, we can make significant strides towards reducing CVD risks and improving population health.

This systematic narrative review sought to comprehensively report evidence related to individual responses to cardiovascular screening interventions. Theoretically, the study builds upon theories based on the cognitive perspective (e.g. Health Belief Model, Protection Motivation Theory), which supports the examination of individual perceptions of negative health-related outcomes or health risk, beliefs regarding the performance of a behaviour or outcome expectancies (e.g. perceived benefits of behavioural performance), personal control or capacity to perform a behaviour and/or willingness to invest the effort to engage in behaviour after behavioural intervention delivery. These concepts are considered key predictors of health-related behaviours and have been examined in several public health interventions. Using a variety of search strategies, studies that reported outcomes of interest were identified. Some studies showed that cardiovascular screening interventions may help people form the desired intention to engage in health-related behaviours. We also observed (largely) encouraging effects of cardiovascular screening interventions on individual confidence to engage in health-related behaviours and understanding of personal health risks. However, we identified some limitations in the design, delivery and outcomes assessed in the studies included. For future research, key recommendations to inform the design and delivery of health behaviour interventions are provided.

Provision of non-invasive coronary and carotid vascular imaging results on changes in diet and physical activity in asymptomatic adults: A scoping review.

Background: Although a healthy diet and physical activity have been shown to prevent or delay cardiovascular disease (CVD) hospitalizations and deaths, most adults do not meet current guidelines. Provision of coronary artery calcification (CAC) and carotid ultrasound (CUS) imaging results may motivate beneficial lifestyle changes. We scoped the existing literature for studies providing non-invasive vascular imaging results and reporting diet, physical activity, and/or anthropometric measures to identify knowledge gaps and opportunities for further research. Methods: A systematic search was performed across three electronic databases, in line with PRISMA ScR guidelines and Arksey and O'Malley's scoping review framework. Results: Twenty studies (thirteen observational and seven randomized controlled trials) examining the impact of provision of CAC/CUS imaging results on diet and/or physical activity behaviors were included. Nearly half the studies did not clearly state whether participants received dietary and physical activity advice along with vascular imaging results, and these were secondary outcomes in most studies, with data assessment and reporting being inconsistent. Conclusion: Well-designed clinical trials with consistent and clear messaging based on detailed subjective and objective measures of diet and physical activity are needed to determine whether this approach may stimulate long-term dietary and physical activity change.

Likeability and perceived effectiveness of messages designed to encourage physical activity participation among older adults.

ISSUE ADDRESSED: Older adults are significantly less likely than their younger counterparts to engage in physical activity. Comprehensive policies to support healthy ageing thus need to include components encouraging greater participation in physical activity in later life. This study tested potential messages for use in health communication campaigns aimed at increasing physical activity among older adults. METHODS: Twelve written messages designed to encourage older adults to increase their levels of physical activity were rated by Australians aged 60-92 years (n = 369; 54% female) on the variables of likeability and perceived effectiveness. RESULTS: Ratings for all the tested messages were high across both outcome variables. The message Move more, live longer scored most favourably, with large majorities of participants liking this message (87%) and considering it effective (81%). Messages featuring rhyming or alliteration were rated significantly higher on both outcomes than messages without these attributes (all Ps < .001). CONCLUSIONS: Results provide insights into the types of messages that are likely to be accepted by older adults. Statements that use the phonological patterns of rhyming or alliteration are likely to be especially well received. SO WHAT?: Increasing participation in physical activity among older adults is critical to promoting the sustainability of health care systems and enhancing quality of life. The specific messaging attributes identified in the present study as being effective could be used by public health practitioners to inform their approach to physical activity messaging to older adults and incorporated into future health communication campaigns to increase their potential effectiveness with this target group.

Delays in the Identification and Assessment of in-Hospital Stroke Patients.

OBJECTIVES: In-hospital stroke is associated with poor outcomes. Reasons for delays, use of interventions, and presence of large vessel occlusion are not well characterized. MATERIALS AND METHODS: A retrospective single center cohort of 97 patients with in-hospital stroke was analyzed to identify factors associated with delays from last known normal to symptom identification and to stroke team alerting. Stroke interventions and presence of large vessel occlusion were also assessed. RESULTS: Strokes were predominantly on surgery services (70%), ischemic (82%), and severe (median NIHSS 16; interquartile range [IQR] 6-24). There were long delays from last known normal to symptom identification (median 5.1 hours, IQR 1.0-19.7 hours), symptom identification to stroke team alerting (median 2.1 hours, IQR 0.5-9.9 hours), and total time from last known normal to alerting (median 11.4 [IQR 2.7-34.2] hours). In univariable analysis, being on a surgical service, in an ICU, intubated, and higher NIHSS were associated with delays. In multivariable analysis only intubation was independently associated with time from last known normal to symptom identification (coefficient 20 hours, IQR 0.2 - 39.8, p=0.047). Interventions were given to 17/80 (21%) ischemic stroke patients; 3 (4%) received IV tPA and 14 (18%) underwent thrombectomy. Vascular imaging occurred in 57/80 (71%) ischemic stroke patients and 21/57 (37%) had large vessel occlusion. CONCLUSIONS: Hospitalized patients with stroke experience long delays from symptom identification to stroke team alerting. Intubation was strongly associated with delay to symptom identification. Although stroke severity was high and large vessel occlusion common, many patients did not receive acute interventions.

Robotics in neurointerventional surgery: a systematic review of the literature.

BACKGROUND: Robotically performed neurointerventional surgery has the potential to reduce occupational hazards to staff, perform intervention with greater precision, and could be a viable solution for teleoperated neurointerventional procedures. OBJECTIVE: To determine the indication, robotic systems used, efficacy, safety, and the degree of manual assistance required for robotically performed neurointervention. METHODS: We conducted a systematic review of the literature up to, and including, articles published on April 12, 2021. Medline, PubMed, Embase, and Cochrane register databases were searched using medical subject heading terms to identify reports of robotically performed neurointervention, including diagnostic cerebral angiography and carotid artery intervention. RESULTS: A total of 8 articles treating 81 patients were included. Only one case report used a robotic system for intracranial intervention, the remaining indications being cerebral angiography and carotid artery intervention. Only one study performed a comparison of robotic and manual procedures. Across all studies, the technical success rate was 96% and the clinical success rate was 100%. All cases required a degree of manual assistance. No studies had clearly defined patient selection criteria, reference standards, or index tests, preventing meaningful statistical analysis. CONCLUSIONS: Given the clinical success, it is plausible that robotically performed neurointerventional procedures will eventually benefit patients and reduce occupational hazards for staff; however, there is no high-level efficacy and safety evidence to support this assertion. Limitations of current robotic systems and the challenges that must be overcome to realize the potential for remote teleoperated neurointervention require further investigation.

Rotavirus NSP1 Inhibits Type I and Type III Interferon Induction.

Type I interferons (IFNs) are produced by most cells in response to virus infection and stimulate a program of anti-viral gene expression in neighboring cells to suppress virus replication. Type III IFNs have similar properties, however their effects are limited to epithelial cells at mucosal surfaces due to restricted expression of the type III IFN receptor. Rotavirus (RV) replicates in intestinal epithelial cells that respond predominantly to type III IFNs, and it has been shown that type III rather than type I IFNs are important for controlling RV infections in vivo. The RV NSP1 protein antagonizes the host type I IFN response by targeting IRF-3, IRF-5, IRF-7, or ß-TrCP for proteasome-mediated degradation in a strain-specific manner. Here we provide the first demonstration that NSP1 proteins from several human and animal RV strains antagonize type III as well as type I IFN induction. We also show that NSP1 is a potent inhibitor of IRF-1, a previously undescribed property of NSP1 which is conserved among human and animal RVs. Interestingly, all NSP1 proteins were substantially more effective inhibitors of IRF-1 than either IRF-3 or IRF-7 which has significance for evasion of basal anti-viral immunity and type III IFN induction in the intestinal epithelium.

'They deserve a treat': the nature and antecedents of parental licensing surrounding children's physical activity.

OBJECTIVE: Little is known about parents' compensatory health beliefs (CHB) surrounding their children's engagement in physical activity (PA). Our aim was to provide evidence regarding the nature of, and factors underpinning, parents' PA-related compensatory beliefs for their children. DESIGN: A qualitative descriptive approach and thematic content analysis were employed. SETTING: Parents were recruited from community sport and PA programmes. PARTICIPANTS: Eighteen parents aged 32-52 years (mean age = 40·8 (sd 5·4) years; six males; twelve females). RESULTS: Analyses indicated that parents compensate through 'passive' or 'active' means. Among parents who compensated, most described their provision of 'treat' foods/drinks and a minority described allowing extended sedentary time to their children. Parents' reasons underpinning these beliefs related to their child's general physical/health status and psychological characteristics, and their own motivation and mood state. CONCLUSIONS: These findings provide the first evidence of unhealthy dietary and sedentary behaviour CHB that parents may hold regarding their children's involvement in PA.

Modification of diet, exercise and lifestyle (MODEL) study: a randomised controlled trial protocol.

INTRODUCTION: Most cardiovascular disease (CVD)-related events could be prevented or substantially delayed with improved diet and lifestyle. Providing information on structural vascular disease may improve CVD risk factor management, but its impact on lifestyle change remains unclear. This study aims to determine whether providing visualisation and pictorial representation of structural vascular disease (abdominal aortic calcification (AAC)) can result in healthful diet and lifestyle change. METHODS AND ANALYSIS: This study, including men and women aged 60-80 years, is a 12-week, two-arm, multisite randomised controlled trial. At baseline, all participants will have AAC assessed from a lateral spine image captured using a bone densitometer. Participants will then be randomised to receive their AAC results at baseline (intervention group) or a usual care control group that will receive their results at 12 weeks. All participants will receive information about routinely assessed CVD risk factors and standardised (video) diet and lifestyle advice with three simple goals: (1) increase fruit and vegetable (FV) intake by at least one serve per day, (2) improve other aspects of the diet and (3) reduce sitting time and increase physical activity. Clinical assessments will be performed at baseline and 12 weeks. OUTCOMES: The primary outcome is a change in serum carotenoid concentrations as an objective measure of FV intake. The study design, procedures and treatment of data will adhere to Standard Protocol Items for Randomized Trials guidelines. ETHICS AND DISSEMINATION: Ethics approval for this study has been granted by the Edith Cowan University and the Deakin University Human Research Ethics Committees (Project Numbers: 20513 HODGSON and 2019-220, respectively). Results of this study will be published in peer-reviewed academic journals and presented in scientific meetings and conferences. Information regarding consent, confidentiality, access to data, ancillary and post-trial care and dissemination policy has been disclosed in the participant information form. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trial Registry (ACTRN12618001087246).

Implementation, mechanisms of impact and key contextual factors involved in outcomes of the Modification of Diet, Exercise and Lifestyle (MODEL) randomised controlled trial in Australian adults: protocol for a mixed-method process evaluation.

INTRODUCTION: The Modification of Diet, Exercise and Lifestyle (MODEL) study aims to examine the impact of providing visualisation and pictorial representation of advanced structural vascular disease (abdominal aortic calcification), on 'healthful' improvements to diet and lifestyle. This paper reports the protocol for the process evaluation for the MODEL study. METHODS AND ANALYSIS: The overall aim of the process evaluation is to understand the processes that took place during participation in the MODEL study trial and which elements were effective or ineffective for influencing 'healthful' behavioural change, and possible ways of improvement to inform wider implementation strategies. A mixed-method approach will be employed with the use of structured questionnaires and semistructured in-depth interviews. All 200 participants enrolled in the trial will undertake the quantitative component of the study and maximum variation sampling will be used to select a subsample for the qualitative component. The sample size for the qualitative component will be determined based on analytical saturation. Interviews will be digitally recorded and transcribed verbatim. Qualitative data will be analysed thematically and reported according to the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines. ETHICS AND DISSEMINATION: The MODEL study process evaluation has received approval from Edith Cowan University Human Research Ethics Committee (Project Number: 20513 HODGSON). Written informed consent will be obtained from all participants before they are included in the study. The study results will be shared with the individuals and institutions associated with this study as well as academic audiences through peer-reviewed publication and probable presentation at conferences. TRIAL REGISTRATION NUMBER: ACTRN12618001087246.

Preliminary Validation of the Exercise-Snacking Licensing Scale: Rewarding Exercise with Unhealthy Snack Foods and Drinks.

There is evidence that individuals' compensatory health beliefs may be an important psychological driver of health behavior. Only recently, however, have researchers begun to develop and seek to validate instruments that are suited to measuring specific pairings of the diverse compensatory health beliefs that exist. The aim of this study was to provide support for key aspects of validity associated with the Exercise-Snacking Licensing Scale (ESLS), an instrument that was designed to assess individuals' endorsement (or licensing) of unhealthy snacking behaviors around exercise. Participants (N = 1095) responded to a version of the ESLS that was designed to assess their licensing responses following either "light" or "tiring" physical activity, and completed additional instruments assessing dispositional, exercise-related, and diet-related constructs. Analyses indicated that scores derived from both versions of the ESLS ("light" and "tiring" physical activity) displayed a relatively consistent factor structure, favorable alpha coefficients, and meaningful correlations with variables that are theoretically aligned with licensing. Factor analytic procedures did, however, indicate that researchers may wish, in future, to consider the use (or not) of reverse-scored items within the ESLS. Together, these findings provide important insight into the structural, external, and generalizability aspects of validity for scores derived from the ESLS, and indicate that the ESLS may be a valuable instrument for the brief assessment of unhealthy licensing beliefs around exercise. Further use of the ESLS is encouraged to determine if and how these licensing beliefs actually influence subsequent snacking behaviors, and the potential downstream effects these beliefs may have in shaping health outcomes associated with exercise participation.

Stand More AT Work (SMArT Work): using the behaviour change wheel to develop an intervention to reduce sitting time in the workplace.

BACKGROUND: Sitting (sedentary behaviour) is widespread among desk-based office workers and a high level of sedentary behaviour is a risk factor for poor health. Reducing workplace sitting time is therefore an important prevention strategy. Interventions are more likely to be effective if they are theory and evidence-based. The Behaviour Change Wheel (BCW) provides a framework for intervention development. This article describes the development of the Stand More AT Work (SMArT Work) intervention, which aims to reduce sitting time among National Health Service (NHS) office-based workers in Leicester, UK. METHODS: We followed the BCW guide and used the Capability, Opportunity and Motivation Behaviour (COM-B) model to conduct focus group discussions with 39 NHS office workers. With these data we used the taxonomy of Behaviour Change Techniques (BCTv1) to identify the most appropriate strategies for facilitating behaviour change in our intervention. To identify the best method for participants to self-monitor their sitting time, a sub-group of participants (n = 31) tested a number of electronic self-monitoring devices. RESULTS: From our BCW steps and the BCT-Taxonomy we identified 10 behaviour change strategies addressing environmental (e.g. provision of height adjustable desks,), organisational (e.g. senior management support, seminar), and individual level (e.g. face-to-face coaching session) barriers. The Darma cushion scored the highest for practicality and acceptability for self-monitoring sitting. CONCLUSION: The BCW guide, COM-B model and BCT-Taxonomy can be applied successfully in the context of designing a workplace intervention for reducing sitting time through standing and moving more. The intervention was developed in collaboration with office workers (a participatory approach) to ensure relevance for them and their work situation. The effectiveness of this intervention is currently being evaluated in a randomised controlled trial. TRIAL REGISTRATION: ISRCTN10967042 . Registered on 2 February 2015.

Precision engineering for PRRSV resistance in pigs: Macrophages from genome edited pigs lacking CD163 SRCR5 domain are fully resistant to both PRRSV genotypes while maintaining biological function.

Porcine Reproductive and Respiratory Syndrome (PRRS) is a panzootic infectious disease of pigs, causing major economic losses to the world-wide pig industry. PRRS manifests differently in pigs of all ages but primarily causes late-term abortions and stillbirths in sows and respiratory disease in piglets. The causative agent of the disease is the positive-strand RNA PRRS virus (PRRSV). PRRSV has a narrow host cell tropism, limited to cells of the monocyte/macrophage lineage. CD163 has been described as a fusion receptor for PRRSV, whereby the scavenger receptor cysteine-rich domain 5 (SRCR5) region was shown to be an interaction site for the virus in vitro. CD163 is expressed at high levels on the surface of macrophages, particularly in the respiratory system. Here we describe the application of CRISPR/Cas9 to pig zygotes, resulting in the generation of pigs with a deletion of Exon 7 of the CD163 gene, encoding SRCR5. Deletion of SRCR5 showed no adverse effects in pigs maintained under standard husbandry conditions with normal growth rates and complete blood counts observed. Pulmonary alveolar macrophages (PAMs) and peripheral blood monocytes (PBMCs) were isolated from the animals and assessed in vitro. Both PAMs and macrophages obtained from PBMCs by CSF1 stimulation (PMMs) show the characteristic differentiation and cell surface marker expression of macrophages of the respective origin. Expression and correct folding of the SRCR5 deletion CD163 on the surface of macrophages and biological activity of the protein as hemoglobin-haptoglobin scavenger was confirmed. Challenge of both PAMs and PMMs with PRRSV genotype 1, subtypes 1, 2, and 3 and PMMs with PRRSV genotype 2 showed complete resistance to viral infections assessed by replication. Confocal microscopy revealed the absence of replication structures in the SRCR5 CD163 deletion macrophages, indicating an inhibition of infection prior to gene expression, i.e. at entry/fusion or unpacking stages.

Does Motivation for Exercise Influence Post-Exercise Snacking Behavior?

It is well established that regular exercise plays an important role in achieving a number of health and wellbeing outcomes. However, certain post-exercise behaviors, including the consumption of unhealthy high-calorie foods, can counteract some of the benefits of physical activity. There are at least three overlapping pathways through which exercise may increase the likelihood of consuming pleasurable but unhealthy foods: through impulsive cognitive processes, reflective cognitive processes, and/or physiological responses. It is argued in this paper that motivation toward exercise can influence each of these pathways. Drawing from literature from various domains, we postulate that controlled exercise motivation, as opposed to autonomous exercise motivation, is more likely to influence each of these pathways in a manner that leaves individuals susceptible to the post-exercise consumption of pleasurable but unhealthy foods.

Risk of septic knee following retrograde intramedullary nailing of open and closed femur fractures.

BACKGROUND: One potential complication of retrograde femoral nailing in the treatment of femur fractures is the risk of septic knee. This risk theoretically increases in open fractures as a contaminated fracture site has the potential to seed the instrumentation being passed in and out of the sterile intraarticular starting point. There are few studies examining this potential complication in a relatively commonly practiced technique. METHODS: All patients who received a retrograde femoral nail for femur fracture between September 1996 and November 2006 at a Level 1 trauma center were retrospectively reviewed. This yielded 143 closed fractures, 38 open fractures and 4 closed fractures with an ipsilateral traumatic knee arthrotomy. Patient follow-up records were reviewed for documentation of septic knee via operative notes, wound culture or knee aspirate data, or the administration of antibiotics for suspected septic knee. RESULTS: No evidence of septic knee was found in the 185 fractures examined in the dataset. Utilizing the Wilson confidence interval, the rate of septic knee based on our population was no greater than 2%, with that of the open fracture group alone being 9%. CONCLUSIONS: Based on these results and review of the literature, the risk of septic knee in retrograde femoral nailing of both open and closed femoral shaft fractures appears low but potentially not insignificant. FUNDING: There was no outside source of funding from either industry or other organization for this study.

Generation of the primary hair follicle pattern.

Hair follicles are spaced apart from one another at regular intervals through the skin. Although follicles are predominantly epidermal structures, classical tissue recombination experiments indicated that the underlying dermis defines their location during development. Although many molecules involved in hair follicle formation have been identified, the molecular interactions that determine the emergent property of pattern formation have remained elusive. We have used embryonic skin cultures to dissect signaling responses and patterning outcomes as the skin spatially organizes itself. We find that ectodysplasin receptor (Edar)-bone morphogenetic protein (BMP) signaling and transcriptional interactions are central to generation of the primary hair follicle pattern, with restriction of responsiveness, rather than localization of an inducing ligand, being the key driver in this process. The crux of this patterning mechanism is rapid Edar-positive feedback in the epidermis coupled with induction of dermal BMP4/7. The BMPs in turn repress epidermal Edar and hence follicle fate. Edar activation also induces connective tissue growth factor, an inhibitor of BMP signaling, allowing BMP action only at a distance from their site of synthesis. Consistent with this model, transgenic hyperactivation of Edar signaling leads to widespread overproduction of hair follicles. This Edar-BMP activation-inhibition mechanism appears to operate alongside a labile prepattern, suggesting that Edar-mediated stabilization of beta-catenin active foci is a key event in determining definitive follicle locations.