Hydrogen Sulfide and Neurogenic Inflammation in Polymicrobial Sepsis: Involvement of Substance P and ERK-NF-κB Signaling

Hydrogen sulfide (H2S) has been shown to induce transient receptor potential vanilloid 1 (TRPV1)-mediated neurogenic inflammation in polymicrobial sepsis. However, endogenous neural factors that modulate this event and the molecular mechanism by which this occurs remain unclear. Therefore, this study tested the hypothesis that whether substance P (SP) is one important neural element that implicates in H2S-induced neurogenic inflammation in sepsis in a TRPV1-dependent manner, and if so, whether H2S regulates this response through activation of the extracellular signal-regulated kinase-nuclear factor-κB (ERK-NF-κB) pathway. Male Swiss mice were subjected to cecal ligation and puncture (CLP)-induced sepsis and treated with TRPV1 antagonist capsazepine 30 minutes before CLP. DL-propargylglycine (PAG), an inhibitor of H2S formation, was administrated 1 hour before or 1 hour after sepsis, whereas sodium hydrosulfide (NaHS), an H2S donor, was given at the same time as CLP. Capsazepine significantly attenuated H2S-induced SP production, inflammatory cytokines, chemokines, and adhesion molecules levels, and protected against lung and liver dysfunction in sepsis. In the absence of H2S, capsazepine caused no significant changes to the PAG-mediated attenuation of lung and plasma SP levels, sepsis-associated systemic inflammatory response and multiple organ dysfunction. In addition, capsazepine greatly inhibited phosphorylation of ERK1/2 and inhibitory κBα, concurrent with suppression of NF-κB activation even in the presence of NaHS. Furthermore, capsazepine had no effect on PAG-mediated abrogation of these levels in sepsis. Taken together, the present findings show that H2S regulates TRPV1-mediated neurogenic inflammation in polymicrobial sepsis through enhancement of SP production and activation of the ERK-NF-κB pathway

Effects of Electrode Design on the Melt Electrowriting of Sinusoidal Structures

Melt electrowriting is a microscale manufacturing technique that uses polymer-based melts to create fibrous structures. An electric field is used to stabilize a continuous molten jet, which is then written onto a substrate as a microscale fiber. Herein, it is investigated how different electrode designs affect the electric field's spatial distribution and intensity. Experiments show that the electrode design affects the temperature of the poly(& epsilon;-caprolactone) melt in the nozzle and plays a crucial role in the formation of jet, its speed, and consequent deposition. A concave electrode design is observed to directly impact the temperature of the polymer being extruded, where it is found to be 10 and 8 & DEG;C lower than the flat and convex electrode, respectively. This lowering in temperature impacts the polymer flow and the critical translation speed directly, impacting the fidelity of prints using a sinusoidal toolpath, showing a reduction of 65% in the programmed value of amplitude. Sinusoid patterns with different amplitudes and wavelengths are designed and printed, providing a library of structures with preprogrammed mechanics for scaffold creation. A high level of control is demonstrated by designing complex alternating amplitude structures displaying dual elastic regions and step-based mechanical properties.LMIS

Natural language processing to measure the frequency and mode of communication between healthcare professionals and family members of critically ill patients

Abstract Objective To apply natural language processing (NLP) techniques to identify individual events and modes of communication between healthcare professionals and families of critically ill patients from electronic medical records (EMR). Materials and Methods Retrospective cohort study of 280 randomly selected adult patients admitted to 1 of 15 intensive care units (ICU) in Alberta, Canada from June 19, 2012 to June 11, 2018. Individual events and modes of communication were independently abstracted using NLP and manual chart review (reference standard). Preprocessing techniques and 2 NLP approaches (rule-based and machine learning) were evaluated using sensitivity, specificity, and area under the receiver operating characteristic curves (AUROC). Results Over 2700 combinations of NLP methods and hyperparameters were evaluated for each mode of communication using a holdout subset. The rule-based approach had the highest AUROC in 65 datasets compared to the machine learning approach in 21 datasets. Both approaches had similar performance in 17 datasets. The rule-based AUROC for the grouped categories of patient documented to have family or friends (0.972, 95% CI 0.934–1.000), visit by family/friend (0.882 95% CI 0.820–0.943) and phone call with family/friend (0.975, 95% CI: 0.952–0.998) were high. Discussion We report an automated method to quantify communication between healthcare professionals and family members of adult patients from free-text EMRs. A rule-based NLP approach had better overall operating characteristics than a machine learning approach. Conclusion NLP can automatically and accurately measure frequency and mode of documented family visitation and communication from unstructured free-text EMRs, to support patient- and family-centered care initiatives. </jats:sec

Acceptability of the Venting Wisely pathway for use in critically ill adults with hypoxaemic respiratory failure and acute respiratory distress syndrome (ARDS): a qualitative study protocol

Introduction Hypoxaemic respiratory failure (HRF) affects nearly 15% of critically ill adults admitted to an intensive care unit (ICU). An evidence-based, stakeholder-informed multidisciplinary care pathway (Venting Wisely) was created to standardise the diagnosis and management of patients with HRF and acute respiratory distress syndrome. Successful adherence to the pathway requires a coordinated team-based approach by the clinician team. The overall aim of this study is to describe the acceptability of the Venting Wisely pathway among critical care clinicians. Specifically, this will allow us to (1) better understand the user’s experience with the intervention and (2) determine if the intervention was delivered as intended.Methods and analysis This qualitative study will conduct focus groups with nurse practitioners, physicians, registered nurses and registered respiratory therapists from 17 Alberta ICUs. We will use template analysis to describe the acceptability of a multicomponent care pathway according to seven constructs of acceptability: (1) affective attitude;,(2) burden, (3) ethicality, (4) intervention coherence, (5) opportunity costs, (6) perceived effectiveness and (7) self-efficacy. This study will contribute to a better understanding of the acceptability of the Venting Wisely pathway. Identification of areas of poor acceptability will be used to refine the pathway and implementation strategies as ways to improve adherence to the pathway and promote its sustainability.Ethics and dissemination The study was approved by the University of Calgary Conjoint Health Research Ethics Board. The results will be submitted for publication in a peer-reviewed journal and presented at a scientific conference.Trial registration number ClinicalTrials.gov NCT04744298