Caenorhabditis elegans as a Model System for Duchenne Muscular Dystrophy

The nematode worm Caenorhabditis elegans has been used extensively to enhance our understanding of the human neuromuscular disorder Duchenne Muscular Dystrophy (DMD). With new arising clinically relevant models, technologies and treatments, there is a need to reconcile the literature and collate the key findings associated with this model

Sulfur amino acid supplementation displays therapeutic potential in a C. elegans model of Duchenne muscular dystrophy

Mutations in the dystrophin gene cause Duchenne muscular dystrophy (DMD), a common muscle disease that manifests with muscle weakness, wasting, and degeneration. An emerging theme in DMD pathophysiology is an intramuscular deficit in the gasotransmitter hydrogen sulfide (H2S). Here we show that the C. elegans DMD model displays reduced levels of H2S and expression of genes required for sulfur metabolism. These reductions can be offset by increasing bioavailability of sulfur containing amino acids (L-methionine, L-homocysteine, L-cysteine, L-glutathione, and L-taurine), augmenting healthspan primarily via improved calcium regulation, mitochondrial structure and delayed muscle cell death. Additionally, we show distinct differences in preservation mechanisms between sulfur amino acid vs H2S administration, despite similarities in required health-preserving pathways. Our results suggest that the H2S deficit in DMD is likely caused by altered sulfur metabolism and that modulation of this pathway may improve DMD muscle health via multiple evolutionarily conserved mechanisms

The associations between rapid response systems and their components with patient outcomes: A scoping review

Background: While rapid response systems have been widely implemented, their impact on patient outcomes remains unclear. Further understanding of their components—including medical emergency team triggers, medical emergency team member composition, additional roles in patient care beyond responding to medical emergency team events, and their involvement in “Do-Not-Resuscitate” order placement—may elucidate the relationship between rapid response systems and outcomes. Objective: To explore how recent studies have examined rapid response system components in the context of relevant adverse patient outcomes, such as in-hospital cardiac arrests and hospital mortality. Design: Scoping review. Methods: PubMed, CINAHL, and Embase were searched for articles published between November 2014 and June 2022. Studies mainly focused on rapid response systems and associations with in-hospital cardiac arrests were considered. The following were extracted for analysis: study design, location, sample size, participant characteristics, system characteristics (including medical emergency team member composition, additional system roles outside of medical emergency team events), medical emergency team triggers, in-hospital cardiac arrests, and hospital mortality. Results: Thirty-four studies met inclusion criteria. While most studies described triggers used, few analyzed medical emergency team trigger associations with outcomes. Of those, medical emergency team triggers relating to respiratory abnormalities and use of multiple triggers to activate the medical emergency team were associated with adverse patient outcomes. Many studies described medical emergency team member composition, but the way composition was reported varied across studies. Of the seven studies with dedicated medical emergency team members, six found their systems were associated with decreased incidence of in-hospital cardiac arrests. Six of seven studies that described additional medical emergency team roles in educating staff in rapid response system use found their systems were associated with significant decreases in adverse patient outcomes. Four of five studies that described proactive rounding responsibilities reported found their systems were associated with significant decreases in adverse patient outcomes. Reporting of rapid response system involvement in “Do-Not-Resuscitate” order placement was variable across studies. Conclusions: Inconsistencies in describing rapid response system components and related data and outcomes highlights how these systems are complex to a degree not fully captured in existing literature. Further large-scale examination of these components across institutions is warranted. Development and use of robust and standardized metrics to track data related to rapid response system components and related outcomes are needed to optimize these systems and improve patient outcomes

Using rapid response system trigger clusters to characterize patterns of clinical deterioration among hospitalized adult patients

Background: Many rapid response system (RRS) events are activated using multiple triggers. However, the patterns in which multiple RRS triggers occur together to activate RRS events are unknown. The purpose of this study was to identify these patterns (RRS trigger clusters) and determine their association with outcomes among hospitalized adult patients. Methods: RRS events among adult patients from January 2015 to December 2019 in the Get With The Guidelines- Resuscitation registry\u27s MET module were examined (n = 134,406). Cluster analysis methods were performed to identify RRS trigger clusters. Pearson\u27s chi-squared and ANOVA tests were used to examine differences in patient characteristics across RRS trigger clusters. Multilevel logistic regressions were used to examine the associations between RRS trigger clusters and outcomes. Results: Six RRS trigger clusters were identified. Predominant RRS triggers for each cluster were: tachypnea, new onset difficulty in breathing, decreased oxygen saturation (Cluster 1); tachypnea, decreased oxygen saturation, staff concern (Cluster 2); respiratory depression, decreased oxygen saturation, mental status changes (Cluster 3); tachycardia, staff concern (Cluster 4); mental status changes (Cluster 5); hypotension, staff concern (Cluster 6). Significant differences in patient characteristics were observed across clusters. Patients in Clusters 3 and 6 had an increased likelihood of in-hospital cardiac arrest (p \u3c 0.01). All clusters had an increased risk of mortality (p \u3c 0.01). Conclusions: We discovered six novel RRS trigger clusters with differing relationships to adverse patient outcomes. RRS trigger clusters may prove crucial in clarifying the associations between RRS events and adverse outcomes and aiding in clinician decision-making during RRS events

Commercial access for UK/ESA student experiments on board the ISS

School students in the US have the ability tocommercially fly experiments on-board the International SpaceStation (ISS) via programmes like the Nanoracks sponsoredStudent Spaceflight Experiment Program (SSEP). Programs likeSSEP do allow international schools to participate but similarprogrammes do not currently exist within the European SpaceAgency (ESA). ESA does, however, support commercial access tospace via companies like Airbus and Kayser Italia. A key principleof SSEP is that students propose to fly experiments that will workwithin existing spaceflight hardware. This is similar to the idea ofusing standardized CubeSat platforms in education and ESA’slong-standing use of standardized Experiment Containers (ECs).These ECs form the starting point for Airbus and Kayser Italia’scommercial access programmes. In 2018 we were selected by theUK Space Agency to develop and fly a UK national payload to theISS. This payload will conduct scientific experiments proposed byourselves, international partners, and schools in the UK. Allexperiments will take place inside ECs that are refurbished, andflight qualified in the UK. If we can successfully conduct studentexperiments during this mission, we will have demonstrated thepossibility of conducting UK student experiments in space via aUK company. This should pave the way for UK-based commercialaccess to the ISS that could be used by schools much like the USbased SSEP.</div