Liposome-encapsulated ISMN: a novel nitric oxide-based therapeutic agent against Staphylococcus aureus biofilms

Background: Staphylococcus aureus in its biofilm form has been associated with recalcitrant chronic rhinosinusitis with significant resistance to conventional therapies. This study aims to determine if liposomal-encapsulation of a precursor of the naturally occurring antimicrobial nitric oxide (NO) enhances its desired anti-biofilm effects against S. aureus, in the hope that improving its efficacy can provide an effective topical agent for future clinical use. Methodology: S. aureus ATCC 25923 biofilms were grown in-vitro using the Minimum Biofilm Eradication Concentration (MBEC) device and exposed to 3 and 60 mg/mL of the NO donor isosorbide mononitrate (ISMN) encapsulated into different anionic liposomal formulations based on particle size (unilamellar ULV, multilamellar MLV) and lipid content (5 and 25 mM) at 24 h and 5 min exposure times. Biofilms were viewed using Live-Dead Baclight stain and confocal scanning laser microscopy and quantified using the software COMSTAT2. Results: At 3 and 60 mg/mL, ISMN-ULV liposomes had comparable and significant anti-biofilm effects compared to untreated control at 24 h exposure (p = 0.012 and 0.02 respectively). ULV blanks also had significant anti-biofilm effects at both 24 h and 5 min exposure (p = 0.02 and 0.047 respectively). At 5 min exposure, 60 mg/mL ISMN-MLV liposomes appeared to have greater anti-biofilm effects compared to pure ISMN or ULV particles. Increasing liposomal lipid content improved the anti-biofilm efficacy of both MLV and ULVs at 5 min exposure. Conclusion: Liposome-encapsulated “nitric oxide” is highly effective in eradicating S. aureus biofilms in-vitro, giving great promise for use in the clinical setting to treat this burdensome infection. Further studies however are needed to assess its safety and efficacy in-vivo before clinical translation is attempted.Camille Jardeleza, Shasha Rao, Benjamin Thierry, Pratik Gajjar, Sarah Vreugde, Clive A. Prestidge, Peter-John Wormal

Assessing resilience against floods with a system dynamics approach: a comparative study of two models

Purpose This paper aims to present the concepts of two different ways of generating a dynamic structure of the urban system to further allow in understanding specific urban behavior facing against flood and further evaluate the potential effect of specific resilience strategies aiming to decrease the exposure and vulnerability of the system. Design/methodology/approach Two system dynamics model structures are presented in form of Casual Loop Diagrams. Findings The main differences among the tow approaches are the time horizon and the approach that regulates the assessment of the resilience through a dynamic composite indicator: the first model refers to baseline at initial simulation time; the second model is focused on the ratio service supply to demand. Research limitations/implications Within the approach, the purpose is to properly and efficiently evaluate the effect of different Flood Risk Management strategies, i.e. prevention, defence, mitigation, preparation and recovery for consistent and resilient flood governance plans with different type of resilience scenarios. Originality/value The need for such tool is underlined by a lack on the assessment of urban resilience to flood as whole, considering the physical and social dimensions and the complex interaction among their main components. There are several assessment tools based on an indicator approach that have been proposed to meet this need. Nevertheless, indicator-based approach has the limitation to exclude the complexity of the system and its systemic interaction in terms of feedbacks’ effects among the identified components or variables selected for the system description. This peculiarity can be provided by System Dynamics modeling

Characterizing College Science Assessments: The Three-Dimensional Learning Assessment Protocol

Citation: Laverty, J. T., Underwood, S. M., Matz, R. L., Posey, L. A., Carmel, J. H., Caballero, M. D., . . . Cooper, M. M. (2016). Characterizing College Science Assessments: The Three-Dimensional Learning Assessment Protocol. Plos One, 11(9), 21. doi:10.1371/journal.pone.0162333Many calls to improve science education in college and university settings have focused on improving instructor pedagogy. Meanwhile, science education at the K-12 level is undergoing significant changes as a result of the emphasis on scientific and engineering practices, crosscutting concepts, and disciplinary core ideas. This framework of "three-dimensional learning" is based on the literature about how people learn science and how we can help students put their knowledge to use. Recently, similar changes are underway in higher education by incorporating three-dimensional learning into college science courses. As these transformations move forward, it will become important to assess three-dimensional learning both to align assessments with the learning environment, and to assess the extent of the transformations. In this paper we introduce the Three-Dimensional Learning Assessment Protocol (3D-LAP), which is designed to characterize and support the development of assessment tasks in biology, chemistry, and physics that align with transformation efforts. We describe the development process used by our interdisciplinary team, discuss the validity and reliability of the protocol, and provide evidence that the protocol can distinguish between assessments that have the potential to elicit evidence of three-dimensional learning and those that do not

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Minitrephination of the frontal sinus: Indications and uses in today's era of sinus surgery

Background: This study reviews the role of frontal sinus minitrephination in today's era of endoscopic sinus surgery. Retrospective chart review was performed of 163 patients undergoing a total of 149 bilateral and 39 unilateral frontal sinus minitrephinations. Methods: Charts were reviewed for patient demographics and outcomes. Details obtained from the chart included type of surgery performed, reason for minitrephination placement, pathology, Lund score, complications and endoscopic patency. Results: One hundred eighty-eight minitrephines were placed during 80 modified Lothrop and 108 frontal sinusotomies. Trephines were placed where there was dificulty finding the frontal recess, severe edema/ polyps, obstructing frontal cells (type3/ type 4 frontoethmoidal cells and intersinus septum cell), and to aid the dissection and postoperative irrigation during the modified Lothrop. Twelve complications occurred with infection at the trephine site being the most common. Follow-up ranged from 2 to 122 months (average, 25.5 months) with 92% showing endoscopic patency at least visit. Conclusion: Frontal sinus trephination is a safe useful procedure that can be extremely helpful in identifying the pathway to the frontal sinus. Fluorscein flushes through the trephine help guide the dissection in a modified Lothrop. Lastly, it may be used in the postoperative period to flush the sinus with saline and steroids to promote patency of the frontal sinus.K Seiberling, C Jardeleza and Peter-John Wormaldhttp://works.bepress.com/peterj_wormald/20

Surgical outcomes of endoscopic management of adenocarcinoma of the sinonasal cavity

Objective: To report the surgical outcomes of endoscopic resection of adenocarcinomas of the Sinonasal cavity. Methods: Retrospective chart review of patients presenting with adenocarcinoma of the anterior skull base between 1998-2008. All patients who underwent wholly endoscopic resection were included in the study. Results: Twelve patients presented with adenocarcinoma involving the sino-nasal cavity. At diagnosis 6 patients were staged as a T2, 5 as a T3 and one as a T4. All of the patients had successful removal of the tumour entirely endoscopically. Three patients recurred: 2 locally and 1 with distant metastases. Overall, 11 patients are alive and free of disease and 1 patient dead of disease. We found an overall disease free survival rate and overall survival rate of 91.6%. The follow-up period ranged from 10 to 96 months with a median of 30 months. Conclusion: Endoscopic management of adenocarcinoma of the sino-nasal cavity can be a viable treatment option to craniofacial resection. With the advancement in endoscopic equipment and surgeon skill, larger tumours may be managed wholly endoscopically.C. Jardeleza, K. Seiberling, S. Floreani, and P.J. Wormaldhttp://www.rhinologyjournal.com/article/article_list.php?mgzn_id=15

Is nasal steroid spray bottle contamination a potential issue in chronic rhinosinusitis?

Background : Intranasal steroids are the first line of treatment for chronic rhinosinusitis. Although contamination of adjunctive devices (e.g. irrigation bottles) has been much investigated, little is known about nasal contamination of the metered-dose spray bottles used to deliver intranasal steroids, and the potential influence on disease chronicity. Methods : Twenty-five prospectively recruited patients with stable chronic rhinosinusitis underwent microbiological analysis of their nasal vestibule and middle meatus and also of their steroid bottle tip and contents. Additionally, bottle tips were inoculated in vitro with Staphylococcus aureus and various sterilisation techniques tested. Results : For 18 of the 25 (72 per cent) patients, both nasal and bottle tip swabs grew either Staphylococcus aureus or coagulase-negative staphylococci. Staphylococcus aureus was cultured from 7 of the 25 (28 per cent) patients, and 5 of these 7 had concomitant bacterial growth from both nose and steroid bottle. Thus, the cross-contamination rate was 71 per cent for Staphylococcus aureus infected patients and 20 per cent overall. Sterilisation was effective with boiling water, ethanol wipes and microwaving, but not with cold water or dishwashing liquid. Conclusion : Nasal steroid spray bottle tips can become contaminated with sinonasal cavity bacteria. Simple sterilisation methods can eliminate this contamination. Patient education on this matter should be emphasised.N C-W Tan, A J Drilling, C Jardeleza, P-J Wormal

Corticosteroids directly reduce Staphylococcus aureus biofilm growth: an in vitro study

Article first published online: 2 OCT 2013Objectives/Hypothesis: Clinical improvement in patients with chronic rhinosinusitis (CRS) treated with steroids alone has previously been ascribed to the steroids' anti-inflammatory properties rather than any direct effect on the bacteria. The aim of this study was to determine if commonly used intranasal steroids directly reduce bacterial biofilm production in vitro. Study Design: In vitro comparative controlled trial. Methods: Staphylococcus aureus biofilms were grown on minimum biofilm eradication concentration device pegs and treated with the commonly prescribed CRS topical steroids fluticasone, mometasone, or budesonide. These were dissolved in vehicle solvents and added to cerebrospinal fluid (CSF) broth. Concentrations (including therapeutic doses) tested for fluticasone and mometasone ranged from 25 μg/200 μL to 400 μg/200 μL, and from 16 μg/200 μL to 2000 μg/200 μL for budesonide. Control pegs were exposed to equivalent volumes of the appropriate solvent/CSF broth. Confocal scanning laser microscopy and COMSTAT software were used to quantify biofilms at 24 hours after treatment. Results: Significant differences from control were found for fluticasone at 400 μg/200 μL (difference = −0.3065 μm3/μm2, P = .007), mometasone at 300 μg/200 μL and 400 μg/200 μL (difference = −0.15 μm3/μm2, P = .006, and difference = −0.9193 μm3/μm2, P = .034, respectively), and budesonide at 750 μg/200 μL, 1000 μg/200 μL and 2000 μg/200 μL (difference = −1.0137 μm3/μm2, P = .038, difference = −0.6164, P = .009, and difference = −0.1906 μm3/μm2, P = .029, respectively). Conclusions: The concentrations of 400 μg/200 μL of fluticasone, 300 μg and 400 μg/200 μL of mometasone, and 750 μg, 1,000μg, and 2,000 μg/200 μL of budesonide directly reduce biofilm production in vitro, outside of the inflammatory milieu.Rachel Goggin, Camille Jardeleza, Peter-John Wormald, Sarah Vreugd

The multiplicity of Staphylococcus aureus in chronic rhinosinusitis: Correlating surface biofilm and intracellular residence

Objectives/hypothesisThe biofilm paradigm of chronic rhinosinusitis (CRS) is increasingly understood to play a key role in the pathophysiology of this disease. The role of intracellular infection of sinonasal epithelial cells has been suggested as a potential reservoir of pathogenic organisms that can lead to recalcitrant disease despite maximal medical and surgical treatment. Could a surface biofilm play a role in allowing intracellular infection to occur, and what are the factors associated with potential intracellular infections? The aim of this study was to investigate these questions.Study designA prospective study including 36 CRS patients undergoing endoscopic sinus surgery and five control patients undergoing endonasal pituitary surgery.MethodsSinonasal mucosa harvested at the time of surgery was examined with a Staphylococcus aureus fluorescence in situ hybridization probe and propodium iodide counterstain using the confocal scanning laser microscope for both biofilm status and evidence of intracellular organisms.ResultsIntracellular S aureus was identified in 20/36 (56%) CRS patients compared to 0/8 (0%) control patients. CRS patients with intracellular infection were significantly more likely to harbor surface biofilm (20/20, P = .0014) and have a S aureus-positive culture swab (12/20, P = .0485).ConclusionsThis study gives further evidence supporting a role of intracellular S aureus in CRS. In all cases intracellular infection was associated with surface biofilm, suggesting a potential relationship between the two. Further work is required to delineate the true mechanisms of intracellular persistence and also the role that it plays in the recalcitrant nature of CRS.Neil C.-W. Tan, Andrew Foreman, Camille Jardeleza, Richard Douglas, Hai Tran, Peter John Wormal

Quantitative analysis of in vivo mucosal bacterial biofilms

Quantitative assays of mucosal biofilms on ex vivo samples are challenging using the currently applied specialized microscopic techniques to identify them. The COMSTAT2 computer program has been applied to in vitro biofilm models for quantifying biofilm structures seen on confocal scanning laser microscopy (CSLM). The aim of this study was to quantify Staphylococcus aureus (S. aureus) biofilms seen via CSLM on ex situ samples of sinonasal mucosa, using the COMSTAT2 program.S. aureus biofilms were grown in frontal sinuses of 4 merino sheep as per a previously standardized sheep sinusitis model for biofilms. Two sinonasal mucosal samples, 10 mm × 10 mm in size, from each of the 2 sinuses of the 4 sheep were analyzed for biofilm presence with Baclight stain and CSLM. Two random image stacks of mucosa with S. aureus biofilm were recorded from each sample, and analyzed using COMSTAT2 software that translates image stacks into a simplified 3-dimensional matrix of biofilm mass by eliminating surrounding host tissue. Three independent observers analyzed images using COMSTAT2 and 3 repeated rounds of analyses were done to calculate biofilm biomass.The COMSTAT2 application uses an observer-dependent threshold setting to translate CSLM biofilm images into a simplified 3-dimensional output for quantitative analysis. Intraclass correlation coefficient (ICC) between thresholds set by the 3 observers for each image stacks was 0.59 (p = 0.0003). Threshold values set at different points of time by a single observer also showed significant correlation as seen by ICC of 0.80 (p < 0.001).COMSTAT2 can be applied to quantify and study the complex 3-dimensional biofilm structures that are recorded via CSLM on mucosal tissue like the sinonasal mucosa.Deepti Singhal, Sam Boase, John Field, Camille Jardeleza, Andrew Foreman, Peter-John Wormal