Electronic Screening for Adolescent Risk Behaviors in the Emergency Department: A Randomized Controlled Trial.

INTRODUCTION: In this study we aimed to assess the impact of an electronic health assessment with individualized feedback for risk behaviors in adolescents seeking care in a pediatric emergency department (ED). METHODS: We conducted a randomized control trial using a tablet-based screening program with a study population of adolescents in a busy pediatric ED. The intervention group received the screening program with individualized feedback. The control group received the screening program without feedback. All participants received one-day and three-month follow-up surveys to assess behaviors and attitudes toward health behaviors. RESULTS: A total of 296 subjects were enrolled and randomized. There was no difference in changes in risky behaviors between the control and experimental groups. A higher proportion of participants in the intervention groups reported that the screener changed the way they thought about their health at one-day follow-up (27.0%, 36/133) compared to the control group (15.5%, 20/129, P = .02). CONCLUSION: This study successfully tested a multivariable electronic health screener in a real-world setting of a busy pediatric ED. The tool did not significantly change risky health behaviors in the adolescent population screened. However, our finding that the intervention changed adolescents' perceptions of their health opens a door to the continued development of electronic interventions to screen for and target risk behaviors in adolescents in the ED setting.

Croup during the Coronavirus Disease 2019 Omicron Variant Surge.

We conducted a retrospective review of medical records of patients with croup seen during the coronavirus disease 2019 pandemic. Approximately 50% underwent testing for severe acute respiratory syndrome coronavirus 2. During the Delta wave, 2.8% of those tested were positive for severe acute respiratory syndrome coronavirus 2; this increased to 48.2% during the Omicron wave, demonstrating a strong correlation between the Omicron variant and croup.

A randomized controlled trial of simulation-based mastery learning to teach the extended focused assessment with sonography in trauma.

BACKGROUND: Mastery learning has gained popularity for training residents in procedural skills due to its demonstrated superiority over traditional methods. However, no studies have compared the efficacy of traditional versus mastery learning methods in residency point-of-care ultrasound education. We hypothesized that mastery learning would improve residents' skills in performing the extended focused assessment with sonography in trauma (eFAST). METHODS: All first-year emergency medicine (EM) resident physicians at a single university hospital underwent a crossover randomized controlled trial to receive mastery-learning eFAST training either at the beginning of the academic year or 6 months into intern year. Participants were taught using a checklist validated by a panel of experts using Mastery Angoff methods and were given feedback on missed tasks until each trainee completed the eFAST with a minimum passing standard (MPS). Our primary outcome was technical proficiency between the two groups for eFAST examinations performed in the emergency department during the academic year. RESULTS: Sixteen interns were enrolled; eight were randomized to each group. The group that received mastery training at the beginning of the year had mean clinical eFAST proficiency scores above the MPS in the first two quarters of the academic year, while the control group did not. Once the control group underwent eFAST mastery training at the midpoint of the year, both groups had mean proficiency scores above the MPS for the remainder of the year. CONCLUSION: Simulation-based mastery learning is an effective method of teaching the eFAST examination. This training during intern orientation conferred early proficiency in clinical performance of eFAST among EM residents. This difference in proficiency was no longer present after the control group received mastery learning education halfway through the academic year.

Evaluation of an Emergency Department High-risk Bruising Screening Protocol.

OBJECTIVES: The objective of this study was to describe the outcomes of implementing a high-risk bruise screening pathway in a pediatric emergency department (ED). METHODS: A retrospective observational study was performed of children aged 0 to <48 months who presented to the ED between December 1, 2016, and April 1, 2019, and had bruising that is high-risk for physical abuse on a nurse screening examination. A high-risk bruise was defined as any bruise if aged <6 months or a bruise to the torso, ears, or neck if aged 6 to <48 months. Records of children with provider-confirmed high-risk bruising were reviewed. RESULTS: Of the 49 726 age-eligible children presenting to the ED, 43 771 (88%) were screened for bruising. Seven hundred eighty-three (1.8%) of those children had positive screen results and 163 (0.4%) had provider-confirmed high-risk bruising. Of the 8635 infants aged <6 months who were screened, 48 (0.6%) had high-risk bruising and 24 of 48 (50%) were classified as cases of likely or definite abuse. Skeletal surveys were performed in 29 of 48 (60%) infants, and 11 of 29 (38%) had occult fracture. Of the 35 136 children aged 6 to <48 months who were screened, 115 of 35 136 (0.3%) had high-risk bruising and 32 of 115 (28%) were classified as cases of likely or definite abuse. CONCLUSIONS: High-risk bruising was rarely present. When infants aged <6 months were evaluated per recommendations, occult fracture was identified in one-third of patients. The screening pathway could help other institutions identify occult injuries in pediatric ED patients.

miR-744-5p contributes to ocular inflammation in patients with primary Sjogrens Syndrome.

In primary Sjögren's syndrome (pSS) the exocrine glands become infiltrated with lymphocytes instigating severe damage to the salivary and lacrimal glands causing dry eyes and dry mouth. Previous investigations have suggested that dysregulated localized and systemic inflammation contributes to the development and pathogenesis of pSS. A miR microarray performed in primary human conjunctival epithelial cells (PECs) demonstrated significant differences in miR expression at the ocular surface between pSS patients and healthy controls. MicroRNA-744-5p (miR-744-5p) was identified as being of particular interest, as its top predicted target is Pellino3 (PELI3), a known negative regulator of inflammation. Validation studies confirmed that miR-744-5p expression is significantly increased in PECs from pSS patients, whilst PELI3 was significantly reduced. We validated the miR-744 binding site in the 3' untranslated region (UTR) of PELI3 and demonstrated that increasing PELI3 levels with a miR-744-5p antagomir in an inflammatory environment resulted in reduced levels of IFN dependent chemokines Rantes (CCL5) and CXCL10. These results reveal a novel role for miR-744-5p in mediating ocular inflammation via Pellino3 expression in pSS patients and suggest that miR-744-5p may be a potential therapeutic target for the management of severe dry eye disease and ocular inflammation in pSS patients.

Systemic IL-1ß production as a consequence of corneal HSV-1 infection-contribution to the development of herpes simplex keratitis.

This study sought to identify potential therapeutic targets in herpes simplex keratitis (HSK) patients with active and inactive infection by investigating peripheral cytokine production. Peripheral blood mononuclear cells (PBMCs) and serum were prepared from healthy controls and HSK patients during active infection or following treatment (inactive infection). Serum antibody titres were determined by ELISA. Protein expression levels were analysed by Western blot. Cytokine levels were determined by multiplex ELISA. Active corneal herpes simplex virus type 1 (HSV-1) infection resulted in significantly elevated peripheral levels of IL-1ß in HSK patients compared to healthy controls, and remained significantly increased following treatment. Elevated production of IL-1ß in inactive patients was associated with significantly increased levels of IRF3 and STAT1, key proteins involved in promoting anti-viral immune responses. Our data suggest that inflammation persists beyond the period that it is clinically evident and that enhanced peripheral production of IL-1ß may have implications for HSV-1 viral clearance in active and inactive HSK patients.

The effects of sedentary behaviour interventions on work-related productivity and performance outcomes in real and simulated office work: A systematic review.

This review examined the impact of environmental, behavioral, and combined interventions to reduce occupational sedentary behaviour on work performance and productivity outcomes. Productivity outcomes were defined as variables assessing work-related tasks (e.g., typing, mouse), whereas performance outcomes were categorized as any variables assessing cognition that did not mimic work-related tasks. Nine databases were searched for articles published up to January 2018. Sixty-three studies were identified that met the inclusion criteria: 45 examined a productivity outcome (i.e., typing, mouse, work-related tasks, and absenteeism), 38 examined a performance outcome (i.e., memory, reading comprehension, mathematics, executive function, creativity, psychomotor function, and psychobiological factors), and 30 examined a self-reported productivity/performance outcome (i.e., presenteeism or other self-reported outcome). Overall, standing interventions do not appear to impact productivity/performance outcomes, whereas walking and cycling interventions demonstrate mixed null/negative associations for productivity outcomes. Hence, standing interventions to reduce occupational sedentary behaviour could be implemented without negatively impacting productivity/performance outcomes.

IL-16/miR-125a axis controls neutrophil recruitment in pristane-induced lung inflammation.

Severe lung inflammation and alveolar hemorrhage can be life-threatening in systemic lupus erythematosus (SLE) patients if not treated early and aggressively. Neutrophil influx is the driver key of this pathology, but little is known regarding the molecular events regulating this recruitment. Here, we uncover a role for IL-16/mir-125a in this pathology and show not only that IL-16 is a target for miR-125a but that reduced miR-125a expression in SLE patients associates with lung involvement. Furthermore, in the pristane model of acute "SLE-like" lung inflammation and alveolar hemorrhage, we observed reduced pulmonary miR-125a and enhanced IL-16 expression. Neutrophil infiltration was markedly reduced in the peritoneal lavage of pristane-treated IL-16-deficient mice and elevated following i.n. delivery of IL-16. Moreover, a miR-125a mimic reduced pristane-induced IL-16 expression and neutrophil recruitment and rescued lung pathology. Mechanistically, IL-16 acts directly on the pulmonary epithelium and markedly enhances neutrophil chemoattractant expression both in vitro and in vivo, while the miR-125a mimic can prevent this. Our results reveal a role for miR-125a/IL-16 in regulating lung inflammation and suggest this axis may be a therapeutic target for management of acute lung injury in SLE.

MicroRNA-302d targets IRF9 to regulate the IFN-induced gene expression in SLE.

Systemic lupus erythematosus (SLE) is a complex disease targeting multiple organs as a result of overactivation of the type I interferon (IFN) system, a feature currently being targeted by multiple biologic therapies against IFN-α. We have identified an estrogen-regulated microRNA, miR-302d, whose expression is decreased in SLE patient monocytes and identify its target as interferon regulatory factor (IRF)-9, a critical component of the transcriptional complex that regulates expression of interferon-stimulated genes (ISGs). In keeping with the reduced expression of miR-302d in SLE patient monocytes, IRF9 levels were increased, as was expression of a number of ISGs including MX1 and OAS1. In vivo evaluation revealed that miR-302d protects against pristane-induced inflammation in mice by targeting IRF9 and hence ISG expression. Importantly, patients with enhanced disease activity have markedly reduced expression of miR-302d and enhanced IRF9 and ISG expression, with miR-302d negatively correlating with IFN score. Together these findings identify miR-302d as a key regulator of type I IFN driven gene expression via its ability to target IRF9 and regulate ISG expression, underscoring the importance of non-coding RNA in regulating the IFN pathway in SLE.

Modeling message preferences: an adaptive conjoint analysis of persuasive messaging to increase fruit and vegetable consumption.

Few past studies have used conjoint analysis to assess message design features and even fewer have looked at health issues. This research applies conjoint analysis to the quest to design motivational messages for African Americans at risk for diet-related adverse health outcomes (e.g., heart disease) in Kentucky. African American health in the state of Kentucky can benefit from a diet high in fruit and vegetable consumption, but little past research has been conducted with African American Kentuckians to explore the best message structure for communicating about increased fruit and vegetable consumption. This study reports on the outcome of the final phase of formative campaign research. We use an adaptive conjoint analysis to identify the most important elements of message design for this group of Kentucky residents. Results indicate that the message's source (i.e., the person delivering the message) is the most important design element for creating persuasive health messaging about fruit and vegetables for African Americans in Kentucky, followed by the stated benefit of eating more fruit and vegetables and the manner in which the behavior is described, respectively. To our knowledge, this study is the first to treat campaign message features as the subject of a conjoint analysis in order to identify which combination of features might be most motivating for a specific target audience. Recommendations for future health communication campaign application, as well as future research are discussed.

Healthicization and Lay Knowledge About Eating Practices in Two African American Communities.

In this manuscript, we expand upon sociological research in lay knowledge about health and healthicization by examining socially mediated ways in which 40 African American adults in two communities acquired information about eating practices. Participants employed a variety of socially informed information-seeking strategies. Many, but not all, used socially prescribed sources exhorting them to maximize their own health and reported an amalgam of experiences concerning their interpretation of healthist messages. Participants variously accepted messages about healthy eating or engaged in strategies of micro-resistance that decentered and/or reinterpreted health promotion discourse. Furthermore, participants used emic community-based resources including those that prioritized familial engagement over individual responsibility in eating practices or that drew upon alternative health practices. We discuss the implications our work has for further research on healthicization and lay knowledge about eating practices, in which community members are actively engaged in meaning-making within local socio-structural contexts.

Asymmetric Isothiourea-Catalysed Formal [3+2] Cycloadditions of Ammonium Enolates with Oxaziridines.

A highly enantioselective Lewis base-catalysed formal [3+2] cycloaddition of ammonium enolates and oxaziridines to give stereodefined oxazolidin-4-ones in high yield is described. Employing an enantioenriched oxaziridine in this process leads to a matched/mis-matched effect with the isothiourea catalyst and allowed the synthesis of either syn- or anti-stereodefined oxazolidin-4-ones in high d.r., yield and ee. Additionally, the oxazolidin-4-one products have been derivatised to afford functionalised enantioenriched building blocks.

Organocatalytic Michael addition-lactonisation of carboxylic acids using α,ß-unsaturated trichloromethyl ketones as α,ß-unsaturated ester equivalents.

Isothiourea HBTM-2.1 catalyses the Michael addition-lactonisation of 2-aryl and 2-alkenylacetic acids and α,ß-unsaturated trichloromethyl ketones. Ring-opening of the resulting dihydropyranones and subsequent alcoholysis of the CCl3 ketone with an excess of methanol gives a range of diesters in high diastereo- and enantioselectivity (up to 95 : 5 dr and >99% ee). Sequential addition of two different nucleophiles to a dihydropyranone gives the corresponding differentially substituted diacid derivative.

Role of DNA/RNA sensors and contribution to autoimmunity.

Innate immune detection and subsequent immune responses rely on the initial recognition of pathogen specific molecular motifs. Foreign nucleic acids are key structures recognised by the immune system, recognition of which occurs mainly through the use of nucleic acid receptors including members of the Toll-like receptors, AIM2-like receptors, RIG-I-like receptors and intracellular DNA receptors. While the immune system is critically important in protecting the host from infection, it is of utmost importance that it is tightly regulated, in order to prevent recognition of self-nucleic acids and the subsequent development of autoimmunity. Defects in the mechanisms regulating such pathways, for example mutations in endonucleases that clear DNA, altered expression of nucleic acid sensors and defects in negative regulators of these signalling pathways involved in RNA/DNA sensing, have all been implicated in promoting the generation of autoimmune responses. This evidence, as reviewed here, suggests that novel therapeutics targeting these sensors and their downstream pathways may be of use in the treatment of patients with autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and primary Sjögren's syndrome.

TRIpartite motif 21 (TRIM21) differentially regulates the stability of interferon regulatory factor 5 (IRF5) isoforms.

IRF5 is a member of the Interferon Regulatory Factor (IRF) family of transcription factors activated downstream of the Toll-Like receptors (TLRs). Polymorphisms in IRF5 have been shown to be associated with the autoimmune disease Systemic Lupus Erythematosus (SLE) and other autoimmune conditions, suggesting a central role for IRF5 in the regulation of the immune response. Four different IRF5 isoforms originate due to alternative splicing and to the presence or absence of a 30 nucleotide insertion in IRF5 exon 6. Since the polymorphic region disturbs a PEST domain, a region associated with protein degradation, we hypothesized that the isoforms bearing the insertion might have increased stability, thus explaining the association of individual IRF5 isoforms with SLE. As the E3 ubiquitin ligase TRIpartite Motif 21 (TRIM21) has been shown to regulate the stability and hence activity of members of the IRF family, we investigated whether IRF5 is subjected to regulation by TRIM21 and whether dysregulation of this mechanism could explain the association of IRF5 with SLE. Our results show that IRF5 is degraded following TLR7 activation and that TRIM21 is involved in this process. Comparison of the individual IRF5 variants demonstrates that isoforms generated by alternative splicing are resistant to TRIM21-mediated degradation following TLR7 stimulation, thus providing a functional link between isoforms expression and stability/activity which contributes to explain the association of IRF5 with SLE.

TRIM68 negatively regulates IFN-ß production by degrading TRK fused gene, a novel driver of IFN-ß downstream of anti-viral detection systems.

In recent years members of the tripartite motif-containing (TRIM) family of E3 ubiquitin ligases have been shown to both positively and negatively regulate viral defence and as such are emerging as compelling targets for modulating the anti-viral immune response. In this study we identify TRIM68, a close homologue of TRIM21, as a novel regulator of Toll-like receptor (TLR)- and RIG-I-like receptor (RLR)-driven type I IFN production. Proteomic analysis of TRIM68-containing complexes identified TRK-fused gene (TFG) as a potential TRIM68 target. Overexpression of TRIM68 and TFG confirmed their ability to associate, with TLR3 stimulation appearing to enhance the interaction. TFG is a known activator of NF-κB via its ability to interact with inhibitor of NF-κB kinase subunit gamma (IKK-γ) and TRAF family member-associated NF-κB activator (TANK). Our data identifies a novel role for TFG as a positive regulator of type I IFN production and suggests that TRIM68 targets TFG for lysosomal degradation, thus turning off TFG-mediated IFN-ß production. Knockdown of TRIM68 in primary human monocytes resulted in enhanced levels of type I IFN and TFG following poly(I:C) treatment. Thus TRIM68 targets TFG, a novel regulator of IFN production, and in doing so turns off and limits type I IFN production in response to anti-viral detection systems.

The association of cytokines with disease activity and damage scores in systemic lupus erythematosus patients.

OBJECTIVE: The aim of this study was to explore the role of cytokines in the pathogenesis of SLE in a genetically homogeneous Caucasian SLE patient population. METHODS: Serum levels of the following cytokines were determined by ELISA in SLE patients (diagnosed as per ACR diagnostic criteria): IL-1ß, IL-10, IL-12p70 and TNF-α. Demographic data, disease activity as per the SLEDAI and damage scores (SLICC) at the 5-year follow-up were calculated. RESULTS: Enhanced production of TNF-α, IL-1 and IL-10 were observed in SLE patients compared with controls. A strong positive correlation was seen between levels of IL-12p70 and IL-10. In addition, IL-10, TNF-α and IL-1 demonstrated a significant relationship with disease activity. Interestingly, elevated levels of IL-10 were observed in SLE patients with CNS involvement while patients with elevated levels of TNF-α were more likely to have renal involvement and sustain damage over the follow-up period. Additionally, the ratio of all cytokines assayed to IL-12p70 levels were significantly higher in SLE patients when compared with controls, with an association seen between damage accrual and the IL-1ß/IL-12p70 ratio (r = 0.431, P = 0.003), IL-10/IL-12p70 ratio (r = 0.351, P = 0.018) and TNF-α/IL-12p70 ratio (r = 0.33, P = 0.028). When the respective ratios were analysed for organ-specific disease, significant differences were observed for the IL-1ß/IL-12p70 ratio (0.79 vs 0.47, P = 0.036), IL-10/IL-12p70 ratio (4.29 vs 1.87, P = 0.018) and TNF-α/IL-12p70 ratio (7.49 vs 5.21, P = 0.018) with respect to renal involvement. CONCLUSION: Increased levels of a number of immunomodulatory cytokines relative to IL-12p70 in this Caucasian SLE patient population are seen in patients with renal involvement and are associated with increased accrual of damage at the 5-year follow-up.

α-Ketophosphonates as ester surrogates: isothiourea-catalyzed asymmetric diester and lactone synthesis.

Isothiourea HBTM-2.1 catalyzes the asymmetric Michael addition/lactonization of aryl- and alkenylacetic acids using α-keto-ß,γ-unsaturated phosphonates as α,ß-unsaturated ester surrogates, giving access to a diverse range of stereodefined lactones or enantioenriched functionalized diesters upon ring-opening.

Btk regulates macrophage polarization in response to lipopolysaccharide.

Bacterial Lipopolysaccharide (LPS) is a strong inducer of inflammation and does so by inducing polarization of macrophages to the classic inflammatory M1 population. Given the role of Btk as a critical signal transducer downstream of TLR4, we investigated its role in M1/M2 induction. In Btk deficient (Btk (-\-)) mice we observed markedly reduced recruitment of M1 macrophages following intraperitoneal administration of LPS. Ex vivo analysis demonstrated an impaired ability of Btk(-/-) macrophages to polarize into M1 macrophages, instead showing enhanced induction of immunosuppressive M2-associated markers in response to M1 polarizing stimuli, a finding accompanied by reduced phosphorylation of STAT1 and enhanced STAT6 phosphorylation. In addition to STAT activation, M1 and M2 polarizing signals modulate the expression of inflammatory genes via differential activation of transcription factors and regulatory proteins, including NF-κB and SHIP1. In keeping with a critical role for Btk in macrophage polarization, we observed reduced levels of NF-κB p65 and Akt phosphorylation, as well as reduced induction of the M1 associated marker iNOS in Btk(-/-) macrophages in response to M1 polarizing stimuli. Additionally enhanced expression of SHIP1, a key negative regulator of macrophage polarisation, was observed in Btk(-/-) macrophages in response to M2 polarizing stimuli. Employing classic models of allergic M2 inflammation, treatment of Btk (-/-) mice with either Schistosoma mansoni eggs or chitin resulted in increased recruitment of M2 macrophages and induction of M2-associated genes. This demonstrates an enhanced M2 skew in the absence of Btk, thus promoting the development of allergic inflammation.