Renewal MI Dental Composite Etch and Seal Properties

This study's aim was to assess whether the Renewal MI composite can self-etch enamel, seal sound cavities, and stabilize demineralized dentine. Etching was assessed using scanning electron microscopy (SEM). Cavity sealing was quantified using the ISO-11405 dye microleakage test. Demineralized dentine stabilization was evaluated by visualizing resin tag formation, enzyme activity and mineral precipitation at the adhesion interface. Renewal MI provided a mild etching of sound enamel in comparison with 37% phosphoric acid. It provided a comparable seal of sound cavities to Z250/Scotchbond Universal adhesive and a superior seal to Activa, Fuji IX and Fuji II LC. With demineralized dentine, Renewal MI formed 300-400 µm resin tags covering 63% of the adhesion interface compared with 55 and 39% for Z250/Scotchbond and Activa. Fuji IX and Fuji II LC formed no resin tags. A higher tag percentage correlated with lower surface enzyme activity. Unlike Activa and Fuji II LC, Renewal MI promoted mineral precipitation from simulated body fluid, occluding adjacent dentinal tubules within 6 months. These novel etching and sealing properties may facilitate Renewal MI's application in minimally invasive dentistry

Long-Acting β<inf>2</inf>-Agonists Increase Fluticasone Propionate-Induced Mitogen-Activated Protein Kinase Phosphatase 1 (MKP-1) in Airway Smooth Muscle Cells

Mitogen-activated protein kinase phosphatase 1 (MKP-1) represses MAPK-driven signalling and plays an important anti-inflammatory role in asthma and airway remodelling. Although MKP-1 is corticosteroid-responsive and increased by cAMP-mediated signalling, the upregulation of this critical anti-inflammatory protein by long-acting β2-agonists and clinically-used corticosteroids has been incompletely examined to date. To address this, we investigated MKP-1 gene expression and protein upregulation induced by two long-acting β2-agonists (salmeterol and formoterol), alone or in combination with the corticosteroid fluticasone propionate (abbreviated as fluticasone) in primary human airway smooth muscle (ASM) cells in vitro. β2-agonists increased MKP-1 protein in a rapid but transient manner, while fluticasone induced sustained upregulation. Together, long-acting β2-agonists increased fluticasone-induced MKP-1 and modulated ASM synthetic function (measured by interleukin 6 (IL-6) and interleukin 8 (IL-8) secretion). As IL-6 expression (like MKP-1) is cAMP/adenylate cyclase-mediated, the long-acting β2-agonist formoterol increased IL-6 mRNA expression and secretion. Nevertheless, when added in combination with fluticasone, β2-agonists significantly repressed IL-6 secretion induced by tumour necrosis factor α (TNFα). Conversely, as IL-8 is not cAMP-responsive, β2-agonists significantly inhibited TNFα-induced IL-8 in combination with fluticasone, where fluticasone alone was without repressive effect. In summary, long-acting β2-agonists increase fluticasone-induced MKP-1 in ASM cells and repress synthetic function of this immunomodulatory airway cell type. © 2013 Manetsch et al

Corticosteroids inhibit sphingosine 1-phosphate-induced interleukin-6 secretion from human airway smooth muscle via mitogen-activated protein kinase phosphatase 1-mediated repression of mitogen and stress-activated protein kinase 1

Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that plays an important proinflammatory role in asthmatic airways. Corticosteroids are first-line antiinflammatories in asthma; however, their repressive effects on S1P-induced cytokine secretion have not been investigated. To address this, our in vitro study reveals the molecular mechanisms by which corticosteroids inhibit S1P-induced IL-6 expression in the pivotal immunomodulatory cell type, airway smooth muscle (ASM). We first uncover the cellular signaling pathways responsible: S1P activates a cyclic adenosine monophosphate/cAMP response-element-binding protein (CREB)/ CRE-dependent pathway to induce IL-6 transcription, concomitant with stimulation of the mitogen-activated protein kinase (MAPK) superfamily and downstream mitogen and stress-activated protein kinase 1 (MSK1) and histone H3 phosphorylation. In this way, S1P stimulates parallel signaling pathways to induce IL-6 secretion via CRE-driven transcription of the IL-6 gene promoter in a relaxed chromatin environment achieved through histone H3 phosphorylation. Second, we investigated how corticosteroids mediate their repressive effects. The corticosteroid dexamethasone inhibits S1P-induced IL-6 protein secretion and mRNA expression, but CREB/CRE transrepression, inhibition of IL-6 mRNA stability, or subcellular relocation of MSK1 were not responsible for the repressive effects of dexamethasone. Rather, we show that dexamethasone rapidly induces up-regulation of the MAPK deactivator MAPK phosphatase 1 (MKP-1) and that MKP-1 blocks the MAPK-driven activation of MSK1 and phosphorylation of histone H3. This was confirmed by treatment with triptolide, an inhibitor of MKP-1 up-regulation, where repressive effects of corticosteroids were reversed. Our study reveals the molecular mechanism underlying the antiinflammatory capacity of corticosteroids to repress proinflammatory functions induced by the potent bioactive sphingolipid S1P in the lung. Copyright © 2014 by the American Thoracic Society

The nucleotide-binding domain and leucine-rich repeat protein-3 inflammasome is not activated in airway smooth muscle upon toll-like receptor-2 ligation

Inflammasomes have emerged as playing key roles in inflammation and innate immunity. A growing body of evidence has suggested that the nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasomeisimportant inchronic airwaydiseases suchas asthma and chronic obstructive pulmonary disease. Inflammasome activation results, in part, in pro-IL-1β processing and the secretion of the proinflammatory cytokine IL-1β. Because asthma exacerbations are associated with elevated concentrations of secreted IL-1β, we addressed whether the NLRP3 inflammasome is activated under in vitro conditions that mimic infectious exacerbations in asthma. Primary cultures of airway smoothmuscle (ASM) cells were treated with infectious stimuli (mimicked using the Toll-like receptor-2 agonist Pam3CSK4, a synthetic bacterial lipopeptide).Whereas Pam3CSK4 robustlyup-regulatedASMcytokineexpressionin response toTNF-αand significantly enhanced IL-1β mRNA expression, we were unable to detect IL-1β in the cell supernatants. Thus, IL-1β was not secreted and therefore was unable to act in an autocrine manner to promote the amplification of ASMinflammatory responses.Moreover, Toll-like receptor-2 ligation did not enhanceNLRP3 or caspase-1 expression in ASM cells, and NLRP3 and caspase-1 protein were not present in the ASM layer of tracheal sections from human donors. In conclusion, these data demonstrate that the enhanced synthetic function of ASM cells, induced by infectious exacerbations of airway inflammation, is NLRP3 inflammasome-independent and IL-1β-independent. Activation of the NLRP3 inflammasome by invading pathogens may prove cell type-specific in exacerbations of airway inflammation in asthma. Copyright © 2013 by the American Thoracic Society

A multistakeholder approach to innovations in NAFLD care

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent globally and requires multidisciplinary care. Here, we report key findings of a NAFLD care workshop, address knowledge gaps and highlight a path to optimise healthcare resource use, to improve outcomes in patients with steatotic liver disease

The implementation of an emergency nursing framework (HIRAID) reduces patient deterioration: A multi-centre quasi-experimental study

Introduction Timely recognition and treatment of acutely ill patients at appropriate levels of the health system are fundamental to the quality and safety of healthcare. This study determines if the implementation of an emergency nursing framework HIRAID (History, Identify Red flags, Assessment, Interventions, Diagnostics, communication and reassessment) improves patient safety. Methods A quasi-experimental cohort study was conducted in two emergency departments in [Anonymised], Australia. HIRAID was implemented using a multi-pronged behaviour change intervention. Data of 920 patients (374 pre and 546 post) who deteriorated within 72-hours of ED departure were collected. Statistical tests were conducted as two-sided, with a 95% confidence interval to determine pre/post cohort association. Results Patients in the post group had more comorbidities, but experienced less deterioration associated with care delivered in the ED (27% to 13%). There was a reduction in treatment delays [ 28.3% to 15.1%, p = 0.041, 95% CI (1.1%–25.3%)], and delay or failure to escalate care when abnormal vital signs were identified [20.2% to6.9%, p = 0.014, 95% CI (3.5%–23.1%)]. Isolated nursing-related causal factors decreased from 20 (21%) to 6 (8%). Conclusions Implementing a standardised emergency nursing framework is associated with a reduction in clinical deterioration related to emergency care

Identification of Patients with Advanced Fibrosis Due to Nonalcoholic Fatty Liver Disease: Considerations for Best Practice

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) prevalence has increased in the past two decades, resulting in a significant but under-recognised public health burden. This impacts the prevalence of advanced fibrosis, end-stage liver disease and associated extrahepatic manifestations. To understand the challenges in recognising patients with advanced fibrosis due to NASH and develop a standardised approach to screen these patients, the authors of this document provided their opinions and expertise from practice and published evidence to identify key challenges and current approaches for diagnosing NASH. The severity of liver fibrosis due to NASH is the main indicator of associated morbidity and mortality outcomes. Therefore, identifying patients with, or at risk of, advanced fibrosis due to NASH and linking them to appropriate care is critical. This can be challenging due to a lack of awareness of NASH among healthcare professionals and a lack of standardised protocols for identifying patients. Simple noninvasive tests may provide an opportunity to facilitate early identification of these patients. This article proposes a simple, universally applicable diagnostic algorithm for use in clinical practice, that includes sequential use of noninvasive tests, ideally a biological marker and an imaging technique, which may help to facilitate early diagnosis of these patients. In the opinion of the authors, early detection of advanced fibrosis is fundamental in the efforts to halt the progression of NASH and diagnostic algorithms may facilitate pre-emptive interventions to curtail the disease

RAAD: LIGHT-1 CubeSat's Payload for the Detection of Terrestrial Gamma-Ray Flashes

The Rapid Acquisition Atmospheric Detector (RAAD), onboard the LIGHT-1 3U CubeSat, detects photons between hard X-rays and soft gamma-rays, in order to identify and characterize Terrestrial Gamma Ray Flashes (TGFs). Three detector configurations are tested, making use of Cerium Bromide and Lanthanum BromoChloride scintillating crystals coupled to photomultiplier tubes or Multi-Pixel Photon Counters, in order to identify the optimal combination for TGF detection. High timing resolution, a short trigger window, and the short decay time of its electronics allow RAAD to perform accurate measurements of prompt, transient events. Here we describe the overview of the detection concept, the development of the front-end acquisition electronics, as well as the ground testing and simulation the payload underwent prior to its launch on December 21st, 2021. We further present an analysis of the detector's in-orbit system behavior and some preliminary results.Comment: 19 pages, 15 figure