Cardiovascular Autonomic Function and Progression of Age-Related Macular Degeneration in The Irish Longitudinal Study of Ageing (TILDA).

Purpose: To examine if changes in hemodynamic measures during an orthostatic challenge were associated with progression of age-related macular degeneration (AMD) over a 4-year period in The Irish Longitudinal Study on Ageing. Methods: Participants with AMD who underwent an active stand (AS) test at wave 1 (2009/2010) and retinal photographs at both wave 1 and wave 3 (2014/2015) were included (N = 159: 121 with no AMD progression and 38 with progression). Beat-to-beat hemodynamic data were non-invasively collected using a Finometer MIDI device during the AS at wave 1, recording systolic blood pressure (sBP), diastolic blood pressure (dBP), mean arterial pressure (MAP), and heart rate. Cardiac output, stroke volume, and total peripheral resistance (TPR) were derived from these measures. Baseline characteristics were compared between groups with and without AMD progression. Mixed-effects linear regression models were used to assess the association between changes in hemodynamic parameters during the AS and AMD progression, controlling for known AMD-associated risk factors. Results: At baseline, increasing age and lower dBP were significantly associated with AMD progression. Mixed-effects models for the period between standing and 10 seconds post-stand revealed significant associations with AMD progression with a steeper drop in dBP and a slower drop in TPR. Between 10 and 20 seconds post-stand, AMD progression was significantly associated with less pronounced reduction in heart rate. Conclusions: These observational data suggest that impaired hemodynamic responses within the first 20 seconds of orthostasis may be associated with the progression of AMD.

CD8+ tissue-resident memory T cells are expanded in primary Sjögren's disease and can be therapeutically targeted by CD103 blockade.

OBJECTIVE: Tissue-resident memory cells (Trm) are a subset of T cells residing persistently and long-term within specific tissues that contribute to persistent inflammation and tissue damage. We characterised the phenotype and function of Trm and the role of CD103 in primary Sjogren's syndrome (pSS). METHODS: In both pSS and non-pSS sicca syndrome patients, we examined Trm frequency, cytokine production in salivary glands (SG) and peripheral blood (PB). We also analysed Trm-related gene expression in SG biopsies through bulk and single-cell RNA sequencing (scRNAseq). Additionally, we investigated Trm properties in an immunisation-induced animal model of pSS (experimental SS, ESS) mouse model and assessed the effects of Trm inhibition via intraglandular anti-CD103 monoclonal antibody administration. RESULTS: Transcriptomic pSS SG showed an upregulation of genes associated with tissue recruitment and long-term survival of Trm cells, confirmed by a higher frequency of CD8+CD103+CD69+ cells in pSS SG, compared with non-specific sialadenitis (nSS). In SG, CD8+ CD103+ Trm contributed to the secretion of granzyme-B and interferon-γ, CD8+ Trm cells were localised within inflammatory infiltrates, where PD1+CD8+ T cells were also increased compared with nSS and MALT lymphoma. scRNAseq of PB and pSS SG T cells confirmed expression of CD69, ITGAE, GZMB, GZMK and HLA-DRB1 among CD3+CD8+ SG T cells. In the SG of ESS, CD8+CD69+CD103+ Trm producing Granzyme B progressively expanded. However, intraglandular blockade of CD103 in ESS reduced Trm, reduced glandular damage and improved salivary flow. CONCLUSIONS: CD103+CD8+Trm cells are expanded in the SG of pSS and ESS, participate in tissue inflammation and can be therapeutically targeted.

The effectiveness and safety of lifestyle medicine and integrative therapies in inflammatory arthritis: an umbrella review using a hierarchical evidence gathering approach.

Objective: An umbrella review was conducted to provide a comprehensive evaluation of the evidence on lifestyle medicine and integrative therapies for inflammatory arthritis. Methods: Five electronic databases were searched for umbrella reviews, meta-analyses, and systematic reviews of randomised controlled trials on acupuncture, diet, exercise, herbal medicine, nutrient supplements, and mind-body therapies for rheumatoid arthritis, spondyloarthritis, and gout published from January 2012 to December 2022. The primary outcomes were functional status and quality of life. Quality assessment was performed using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) tool, and the certainty of evidence for our primary outcomes was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach where possible. Results: We included 52 reviews. Exercise was beneficial for functional status in both rheumatoid arthritis and spondyloarthritis, with moderate certainty of evidence. Chinese herbal medicine in combination with disease-modifying anti-rheumatic drugs may improve functional status in rheumatoid arthritis (very low certainty evidence). Acupuncture may improve functional status in rheumatoid arthritis and pain in both rheumatoid arthritis and gout; however, the evidence is of very low certainty. Evidence for other therapies was not clinically significant; however, it suggests possible benefits from quercetin and polyunsaturated fatty acids. Yoga may result in a moderate improvement in functional status when used as an adjunct to medication; however, the certainty of evidence is very low. Diet interventions offered inconsistent improvements to functional status in rheumatoid arthritis, spondyloarthritis, and gout with low to very low certainty. Conclusion: Exercise should be prescribed for people with rheumatoid arthritis and spondyloarthritis. More research is needed to confirm or refute evidence for Chinese herbal medicine, acupuncture, yoga, and anti-inflammatory diets.

Nutritional interventions during treatment for ovarian cancer: A narrative review and recommendations for future research.

Most women with ovarian cancer are diagnosed at an advanced stage (stage III or IV), when the intraabdominal spread of the tumour impacts nutrient intake and absorption. Up to 70 % of women with ovarian cancer are malnourished and approximately 40 % are affected by muscle loss at the time of diagnosis. Women with ovarian cancer are at high risk of nutritional decline due to invasive treatment and the severity of side-effects. This review explores the evidence evaluating nutritional interventions during treatment for ovarian cancer and their effect on nutritional status, muscle mass, and clinical outcomes. Perioperative immunonutrition has been investigated with mixed results for immediate postoperative outcomes. Individualised nutrition counselling as part of a multimodal prehabilitation programme prior to surgery shows promising results; however, the effects are limited by sample size. Nutrition counselling as part of a mixed intervention with exercise shows high acceptability and suggests improvements in dietary intake and quality of life during chemotherapy treatment, while oral nutritional supplements and nutrition education appear to reduce symptom burden. Individualised nutrition counselling during treatment also appears to be associated with improved overall survival; however, the evidence is limited to a single retrospective study. A key finding from this review is that, despite the high prevalence of malnutrition and muscle loss in women with ovarian cancer and the critical importance of addressing these modifiable prognostic factors, nutrition intervention studies are limited. Prospective studies with samples large enough to provide adequate power to evaluate intervention effectiveness are urgently required to inform optimal management.

Pragmatic Adaptive Trial for Respiratory Infection in Children (PATRIC) Clinical Registry protocol.

INTRODUCTION: Acute respiratory infections (ARI) are the most common cause of paediatric hospitalisation. There is an urgent need to address ongoing critical knowledge gaps in ARI management. The Pragmatic Adaptive Trial for Respiratory Infections in Children (PATRIC) Clinical Registry will evaluate current treatments and outcomes for ARI in a variety of paediatric patient groups. The registry will provide a platform and data to inform a number of PATRIC clinical trials, testing various interventions in ARI treatment and management to optimise paediatric ARI care. METHODS AND ANALYSIS: The PATRIC Clinical Registry is a single-centre, prospective observational registry recruiting from a tertiary paediatric Emergency Department in Western Australia. Through characterising demographic, clinical, treatment and outcome data, the PATRIC Clinical Registry will improve our understanding of antibiotic utilisation and ARI outcomes in children. ETHICS AND DISSEMINATION: The PATRIC Clinical Registry is conducted in accordance with the Declaration of Helsinki, and the International Council for Harmonisation (ICH) Guidelines for Good Clinical Practice (CPMP/ICH/13595) July 1996. Approval is provided by the Child and Adolescent Health Service Human Research Ethics Committee (HREC). Study results will be communicated by presentation and publication (HREC: RGS0000003078.) TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12619000903189. UTN: U1111-1231-3365.

Access to nutrition services and information after active cancer treatment: a mixed methods study.

PURPOSE: Evidence-based guidelines for cancer strongly support nutrition and dietetic services for people with cancer and carers in order to improve patient-centred and health service outcomes. Access to nutrition services and information after completing active cancer treatment is relatively unknown in Australia. This study aimed to determine the availability, accessibility, barriers, and preferences to nutrition services and information after cancer treatment in Australia. METHODS: Utilising mixed methods, people with cancer and carers completed a cross-sectional survey, and a sub-group of participants completed a semi-structured interview. The survey evaluated the availability of nutrition services, nutrition information searched, barriers, and preferences for nutrition information. Semi-structured interviews explored participant experience with nutrition services and information. RESULTS: The 149 participants (including 10 carers) were predominately male and with a diagnosis of prostate cancer (63%). Overall, 23% of participants received nutrition information from a dietitian after cancer treatment. Participants (78%) indicated that accessing a nutrition specialist is the main barrier to receiving nutrition care after treatment. Most searched nutrition information on the internet (55%) and found the information easy to understand (89%), but conflicting (52%). Thematic analysis of interviews in fourteen cancer patients revealed three key themes pertaining to (1) preferred referral and timing of nutrition services, (2) lack of confidence in publicly available nutrition information, and (3) streamlining nutrition services for greater access. CONCLUSION: Access to a dietitian and evidence-based information after cancer treatment is limited for people with cancer and carers in Australia, despite the high interest and need for ongoing nutrition care. IMPLICATIONS FOR CANCER SURVIVORS: Models of care evaluating the provision of appropriate nutrition care and information provision after cancer treatment are needed to address this unmet survivorship need.

Impact of Bifidobacterium longum1714® on maternal cytokine response in peripheral blood mononuclear cells.

PURPOSE: The maternal immune system is implicated in adverse pregnancy outcomes. Manipulation of maternal immune response by probiotics holds potential to reduce pregnancy complications. The MicrobeMom2 study investigates the impact of probiotic supplementation on maternal immune responses to pathogen associated molecular patterns (PAMPs) in peripheral blood mononuclear cells (PBMCs) during pregnancy. METHODS: This double-blinded randomised-controlled trial involved oral supplementation of Bifidobacterium longum subsp. longum 1714® (B. longum 1714; daily ingestion of a minimum of 1x109 colony forming units) or placebo from 16 to 20-weeks' gestation until delivery in healthy pregnant women. The primary outcome was a change in IL-10 production, after stimulation with Lipopolysaccharide (LPS) or anti-CD3/28/2, in PBMCs isolated from blood samples taken at baseline (11-15 weeks' gestation) and late pregnancy (28-32 weeks' gestation) after 48 h incubation. 68 subjects were needed (34ineachgroup) for 80 % power at an alpha significance of 0.05 to detect differences in IL10. RESULTS: 72 women (mean ± SD age 33.17 ± 4.53 years and median (25th, 75th centile) body mass index 24.93 (21.93, 27.57 kg/m2)) were recruited with primary outcome data. Using LPS, late pregnancy fold change in IL-10 in PBMCs after 48 h incubation was median (25th, 75th centile) 88.45 (4.88, 488.78) in the intervention, 24.18 (6.36, 141.17) in the control group, p = 0.183. Using anti-CD3/28/2, values were 189.69 (425.96, 866.57),148.74 (31.67, 887.03) in intervention and control groups, respectively, p = 0.506. No significant differences were observed between the two groups. CONCLUSION: Maternal antenatal supplementation with B. longum 1714 did not alter cytokine production by maternal PBMCs in response to PAMPs or anti-CD3/28/2. TRIAL REGISTRATION NUMBER: ISRCTN registry ISRCTN43013285.

Sorry to ask but how is apology effectiveness dependent on apology content and gender?

While it is well understood that the content included in an apology matters, what constitutes an effective apology may differ depending on the gender of the person delivering it. In this article, we test competing theoretical perspectives (i.e., role congruity theory and expectancy violation theory [EVT]) about the relative effectiveness of apologies that include language that conforms (or not) with the gender stereotypes ascribed to the apologizer. Results of four studies supported an EVT perspective and showed that apologies were perceived to be relatively more effective when they contradicted gender stereotypes (i.e., communal [agentic] apologies by men [women]). Specifically, Study 1 provided an initial test of the competing hypotheses using celebrity apologies on Twitter. Then, results of three experiments (Studies 2, 3a, and 3b) built upon these initial findings and tested the psychological mechanisms proposed by EVT to explain why counterstereotypical apologies are beneficial (i.e., attributions of interpersonal sensitivity [assertiveness] and enhanced perceptions of benevolence [competence] for men [women]). Our contributions to theory and practice are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

MALDI and Trace Metal Analysis in Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) remains one of the most prevalent causes of blindness throughout the world. Key to prevention of AMD is furthering the understanding of its pathology. In recent years, both the proteins within the innate immune system and essential and non-essential metals have been implicated in the pathology of AMD. Herein, a multidisciplinary and multimodal methodology has been taken to further our understanding of the role of the innate immune proteins and the essential metals within mouse ocular tissue.

Are We Essential, or Sacrificial? The Effects of Felt Public Gratitude on Essential Worker Recovery Activities During COVID-19.

COVID-19 has been characterized by unprecedented levels of public gratitude to some, but not all, essential workers. In this research, we integrate insights from the stigmatized occupations and gratitude literature to build theory on the positive and negative relationships between such displays of public gratitude and essential workers' recovery activities. We argue that felt public gratitude positively relates to adaptive recovery activities (e.g., exercise) and negatively relates to maladaptive recovery activities (e.g., overdrinking). We further explain how felt public gratitude impacts (mal)adaptive recovery activities through (a) felt invisibility and (b) negative/positive affect. We find support for our predictions in a two-wave survey of 186 corrections officers (Study 1) and an experiment with 379 essential workers across a variety of industries (Study 2).

Cross-sectional survey of compliance behaviour, knowledge and attitudes among cases and close contacts during COVID-19 pandemic.

Objectives: A key public health intervention is self-isolation for cases and restriction of movement for contacts. This study aimed to identify predictors of compliance behaviour and describe knowledge and attitudes among cases and contacts identified by the national Contact Management Programme to inform the global public health response. Study design: Secondary data analysis of anonymised cross-sectional survey data on national sample of cases and close contacts. Methods: A sample of 1000 cases and 1000 contacts was calculated to estimate compliance within a margin of error of 3% with 95% confidence. A telephone survey administered by trained interviewers collected information on socio-demographics, compliance behaviours, knowledge, and attitudes to COVID-19 from cases and close contacts. Data analysis included chi-squared statistics and multivariable logistic regression. Results: Most cases and contacts complied with public health guidance with similar characteristics in those who did and did not comply. Reasons for non-compliance included exercise, medical appointment, shopping, and work. Cases and contacts reported high levels of understanding about symptoms of COVID-19 and satisfaction with available information. Conclusion: Achieving high compliance with public health guidance is feasible and requires political leadership, policy changes and practical solutions.

Geochemical controls on mobilization of metals from a 100-year-old waste rock pile and implications for selection of cover amendments.

Reclamation of mine waste rock piles typically consists of constructing a cover with amendments to improve conditions for vegetation. However, cover amendments have potential to mobilize metals in waste by introducing new chemicals and altering pH and redox conditions. This study evaluates metal phases in a 100-year-old waste rock pile with high metals content (3.5% lead by weight, 0.8% zinc, and 0.75% copper) and the potential for these metals to be mobilized by several cover materials and amendments (topsoil, spent brewery grain, biochar, compost, commercial soil media, and phosphate). Laboratory testing indicates that metals have weathered from their initial metal sulfide phases (galena, sphalerite, chalcopyrite), and are now also present as sulfates, phosphates, carbonates, and phases associated with manganese/iron oxides. Sequential extraction tests demonstrated that the largest extractable fraction of metals is associated with manganese/iron oxides (37% of lead by weight, 22% of copper, and 26% of zinc), suggesting an environmental risk should geochemically reducing conditions develop and mobilize metals in the pile after cover construction. Testing of specific cover materials demonstrated that metals mobilization also occurs from low pH (as with spent brewery grain), formation of stable aqueous metal-organic complexes (as with spent brewery grain and compost), and ligand exchange (as with phosphate amendment). Results of this study demonstrate the importance of identifying metal phases present in a waste rock pile prior to selecting cover amendments.

Multiomic Mass Spectrometry Imaging to Advance Future Pathological Understanding of Ocular Disease.

Determining the locations of proteins within the eye thought to be involved in ocular pathogenesis is important to determine how best to target them for therapeutic benefits. However, immunohistochemistry is limited by the availability and specificity of antibodies. Additionally, the perceived role of both essential and non-essential metals within ocular tissue has been at the forefront of age-related macular degeneration (AMD) pathology for decades, yet even key metals such as copper and zinc have yet to have their roles deconvoluted. Here, mass spectrometry imaging (MSI) is employed to identify and spatially characterize both proteomic and metallomic species within ocular tissue to advance the application of a multiomic imaging methodology for the investigation of ocular diseases.

Evaluation of the Dose-Dependent Inflammatory Response and No-Observable Adverse Effect Level of Intravitreal Endotoxin in the African Green Monkey.

Purpose: To evaluate the inflammatory effects and no-observed adverse effect level (NOAEL) of intravitreal endotoxin in an African green monkey model of uveitis. Methods: Fifteen green monkeys were administered intravitreal endotoxin ranging from 0.005 to 0.08 endotoxin unit (EU)/eye. Inflammation was evaluated by slit-lamp biomicroscopy, indirect fundoscopy, tonometry, color fundus photography, ocular coherence tomography, laser flare photometry, and histopathology, with analysis of cytokine levels in aqueous and vitreous humor. The inter-rater reliability of a refined nonhuman primate ophthalmic scoring system was evaluated. Results: A dose-dependent inflammatory response was observed beginning at 0.02 EU/eye; no inflammatory response exceeding the vehicle was observed at 0.005 EU/eye. Retinal pathology was minimal, and posterior visualization degraded with increasing inflammation. Inflammation was observed by histopathology at 0.04 EU/eye. Inter-rater reliability of the scoring system was high, with 99.2% of individual scores differing by 1 scale unit or less and 87.2% of summary scores differing by 2 scale units or less. Conclusions: The NOAEL for intravitreal endotoxin in the green monkey is 0.005 EU/eye, with inflammation increasing with increasing dose beginning at 0.02 EU/eye. This updated nonhuman primate ophthalmic scoring system allows for high inter-rater reliability for the quantification of mild to severe inflammation in the green monkey eye. Translational Relevance: Validation of the ophthalmic inflammation scoring system enables application of the green monkey as a valuable translational model. Candidate therapeutics should be confirmed to have endotoxin levels below this threshold before safety testing in this species to enable interpretation of inflammation and minimize impact on animal welfare.

Staphylococcus aureus-induced immunosuppression mediated by IL-10 and IL-27 facilitates nasal colonisation.

Staphylococcus aureus persistently colonises the anterior nares of a significant proportion of the healthy population, however the local immune response elicited during S. aureus nasal colonisation remains ill-defined. Local activation of IL-17/IL-22 producing T cells are critical for controlling bacterial clearance from the nasal cavity. However, recurrent and long-term colonisation is commonplace indicating efficient clearance does not invariably occur. Here we identify a central role for the regulatory cytokine IL-10 in facilitating bacterial persistence during S. aureus nasal colonisation in a murine model. IL-10 is produced rapidly within the nasal cavity following S. aureus colonisation, primarily by myeloid cells. Colonised IL-10-/- mice demonstrate enhanced IL-17+ and IL-22+ T cell responses and more rapidly clear bacteria from the nasal tissues as compared with wild-type mice. S. aureus also induces the regulatory cytokine IL-27 within the nasal tissue, which acts upstream of IL-10 promoting its production. IL-27 blockade reduces IL-10 production within the nasal cavity and improves bacterial clearance. TLR2 signalling was confirmed to be central to controlling the IL-10 response. Our findings conclude that during nasal colonisation S. aureus creates an immunosuppressive microenvironment through the local induction of IL-27 and IL-10, to dampen protective T cell responses and facilitate its persistence.

SARM1 Promotes Photoreceptor Degeneration in an Oxidative Stress Model of Retinal Degeneration.

SARM1 (sterile alpha and armadillo motif-containing protein) is a highly conserved Toll/IL-1 Receptor (TIR) adaptor with important roles in mediating immune responses. Studies in the brain have shown that SARM1 plays a role in induction of neuronal axon degeneration in response to a variety of injuries. We recently demonstrated that SARM1 is pro-degenerative in a genetic model of inherited retinopathy. This current study aimed to characterise the effect of SARM1 deletion in an alternative model of retinal degeneration (RD) in which the retinal pigment epithelium (RPE) fragments following administration of oxidising agent, sodium iodate (NaIO3), leading to subsequent photoreceptor cell death. Following administration of NaIO3, we observed no apparent difference in rate of loss of RPE integrity in SARM1 deficient mice compared to WT counterparts. However, despite no differences in RPE degeneration, photoreceptor cell number and retinal thickness were increased in Sarm1-/- mice compared to WT counterparts. This apparent protection of the photoreceptors in SARM1 deficient mice is supported by an observed decrease in pro-apoptotic caspase-3 in the photoreceptor layer of Sarm1-/- mice compared to WT. Together these data indicate a pro-degenerative role for SARM1 in the photoreceptors, but not in the RPE, in an oxidative stress induced model of retinal degeneration consistent with its known degenerative role in neurons in a range of neurodegenerative settings.

Transmission of SARS-CoV-2 arising from international flights arriving in Ireland in December 2020: a descriptive analysis using national surveillance data.

OBJECTIVES: There is limited evidence on the risk of in-flight transmission of SARS-CoV-2. This study estimated the extent of in-flight SARS-CoV-2 transmission on international flights arriving in Ireland during December 2020. STUDY DESIGN: This was a cross-sectional analysis. METHODS: National surveillance data identified all notified cases of COVID-19 who were infectious while travelling on international flights to Ireland during December 2020. Close contacts of cases were tested for SARS-CoV-2, and the results were collated to estimate the pooled secondary attack rate across all flights. Laboratory and epidemiological data were obtained from the Health Service Executive Covid Care Tracker, a national database of COVID-19 cases in Ireland. RESULTS: A total of 165 infectious cases of COVID-19 were identified on 134 incoming flights; 40.0% were symptomatic on board. There were 2099 flight close contacts identified, of whom 40.9% had results of a SARS-CoV-2 polymerase chain reaction test within 14 days of arrival. The pooled secondary attack rate for these contacts was 7.0% and was higher among those on flights of ≥5-hour duration (P = 0.008). More than half (59.1%) of close contacts had no SARS-CoV-2 test result recorded; the reasons included incorrect or absent contact details (26.5%) and no response when contacted (17.8%). CONCLUSIONS: In this national study investigating transmission of SARS-CoV-2 from international flights arriving into Ireland, the pooled secondary attack rate was 7.0%. International travel is likely to have contributed to the third wave of SARS-CoV-2 infections in Ireland in early 2021. Application of non-pharmaceutical interventions remains central to mitigating the risk of in-flight transmission.

Efficacy of Digital Health Tools for a Pediatric Patient Registry: Semistructured Interviews and Interface Usability Testing With Parents and Clinicians.

BACKGROUND: Acute respiratory infection (ARI) in childhood is common, but more knowledge on the burden and natural history of ARI in the community is required. A better understanding of ARI risk factors, treatment, and outcomes will help support parents to manage their sick child at home. Digital health tools are becoming more widely adopted in clinical care and research and may assist in understanding and managing common pediatric diseases, including ARI, in hospitals and in the community. We integrated 2 digital tools-a web-based discharge communication system and the REDCap (Research Electronic Data Capture) platform-into the Pragmatic Adaptive Trial for Acute Respiratory Infection in Children to enhance parent and physician engagement around ARI discharge communication and our patient registry. OBJECTIVE: The objective of this study is to determine the efficacy and usability of digital tools integrated into a pediatric patient registry for ARI. METHODS: Semistructured interviews and software interface usability testing were conducted with 11 parents and 8 emergency department physicians working at a tertiary pediatric hospital and research center in Perth, Western Australia, in 2019. Questions focused on experiences of discharge communication and clinical trial engagement. Responses were analyzed using the qualitative Framework Method. Participants were directly observed using digital interfaces as they attempted predetermined tasks that were then classified as success, failure, software failure, or not observed. Participants rated the interfaces using the System Usability Scale (SUS). RESULTS: Most parents (9/11, 82%) indicated that they usually received verbal discharge advice, with some (5/11, 45%) recalling receiving preprinted resources from their physician. Most (8/11, 73%) would also like to receive discharge advice electronically. Most of the physicians (7/8, 88%) described their usual practice as verbal discharge instructions, with some (3/8, 38%) reporting time pressures associated with providing discharge instructions. The digital technology option was preferred for engaging in research by most parents (8/11, 73%). For the discharge communication digital tool, parents gave a mean SUS score of 94/100 (SD 4.3; A grade) for the mobile interface and physicians gave a mean usability score of 93/100 (SD 4.7; A grade) for the desktop interface. For the research data management tool (REDCap), parents gave a mean usability score of 78/100 (SD 11.0; C grade) for the mobile interface. CONCLUSIONS: Semistructured interviews allowed us to better understand parent and physician experiences of discharge communication and clinical research engagement. Software interface usability testing methods and use of the SUS helped us gauge the efficacy of our digital tools with both parent and physician users. This study demonstrates the feasibility of combining qualitative research methods with software industry interface usability testing methods to help determine the efficacy of digital tools in a pediatric clinical research setting.

Cytosolic dsRNA improves neonatal innate immune responses to adjuvants in use in pediatric vaccines.

Pattern recognition receptors (PRRs) of the innate immune system represent the critical front-line defense against pathogens, and new vaccine formulations target these PRR pathways to boost vaccine responses, through activation of cellular/Th1 immunity. The majority of pediatric vaccines contain aluminum (ALUM) or monophosphoryl lipid A (MPLA) as adjuvants to encourage immune activation. Evidence suggests that elements of the innate immune system, currently being targeted for vaccine adjuvanticity do not fully develop until puberty and it is likely that effective adjuvants for the neonatal and pediatric populations are being overlooked due to modeling of responses in adult systems. We recently reported that the activity of the cytosolic nucleic acid (CNA) sensing family of PRRs is strong in cord blood and peripheral blood of young children. This study investigates the function of CNA sensors in subsets of neonatal innate immune cells and shows that myeloid cells from cord blood can be activated to express T cell costimulatory markers, and also to produce Th1 promoting cytokines. CD80 and CD86 were consistently up-regulated in response to cytosolic Poly(I:C) stimulation in all cell types examined and CNA activation also induced robust Type I IFN and low levels of TNFα in monocytes, monocyte-derived macrophages, and monocyte-derived dendritic cells. We have compared CNA activation to adjuvants currently in use (MPLA or ALUM), either alone or in combination and found that cytosolic Poly(I:C) in combination with MPLA or ALUM can improve expression of activation marker levels above those observed with either adjuvant alone. This may prove particularly promising in the context of improving the efficacy of existing ALUM- or MPLA-containing vaccines, through activation of T cell-mediated immunity.