Plasma membrane preassociation drives ß-arrestin coupling to receptors and activation.

ß-arrestin plays a key role in G protein-coupled receptor (GPCR) signaling and desensitization. Despite recent structural advances, the mechanisms that govern receptor-ß-arrestin interactions at the plasma membrane of living cells remain elusive. Here, we combine single-molecule microscopy with molecular dynamics simulations to dissect the complex sequence of events involved in ß-arrestin interactions with both receptors and the lipid bilayer. Unexpectedly, our results reveal that ß-arrestin spontaneously inserts into the lipid bilayer and transiently interacts with receptors via lateral diffusion on the plasma membrane. Moreover, they indicate that, following receptor interaction, the plasma membrane stabilizes ß-arrestin in a longer-lived, membrane-bound state, allowing it to diffuse to clathrin-coated pits separately from the activating receptor. These results expand our current understanding of ß-arrestin function at the plasma membrane, revealing a critical role for ß-arrestin preassociation with the lipid bilayer in facilitating its interactions with receptors and subsequent activation.

KidzMed e-learning to upskill student pharmacists to teach pill swallowing to children.

BACKGROUND: Appropriate medication use is essential in ensuring optimal pharmacotherapeutic outcomes. It is mistakenly assumed that adults can swallow solid oral dosage forms (SODFs, e.g. tablets/capsules colloquially referred to as 'pills'), without difficulty and that children cannot. KidzMed is a 'pill swallowing' training programme designed to teach effective SODF use in patients of all ages. It may be utilised by healthcare professionals to assist patients taking SODFs. E-learning was essential for training during COVID pandemic to reduce viral transmission. The aim of this study was to explore UK student pharmacists views of e-learning to support swallowing solid oral dosage forms. METHODS: This study used pre- and post-intervention online surveys on Microsoft Forms to evaluate self-directed eLearning about pill swallowing on MPharm programmes at three UK Universities using a 13-item survey. A combination of five-point Likert Scales and free-text items were used. The eLearning was available via the virtual learning environment at the University and embedded within existing curriculum. Descriptive statistical analysis was used to explore responses. RESULTS: In total, 113 of 340 (33%) students completed the survey. Seventy-eight percent (n = 65) reported the eLearning would enable them to teach adults and children to swallow SODFs successfully. Learners either agreed or strongly agreed that they felt comfortable to teach patients (95%, n = 62/113) and parents or carers (94%, n = 60) to swallow medications having completed the e-learning. Student pharmacists generally found eLearning as an acceptable way to reflect on their own experiences of 'pill' swallowing and how to support patients to swallow SODFs. CONCLUSION: The KidzMed eLearning was well received by student pharmacists. Further work is needed to explore whether skills translates into real life application in the clinical settings.

A survey of self-reported use of cricoid pressure amongst Australian and New Zealand anaesthetists: Attitudes and practice.

We conducted a survey of Australian and New Zealand anaesthetists designed to quantify self-reported use of cricoid pressure (CP) in patients presumed to be at risk of gastric regurgitation, and to ascertain the underlying justifications used to support individual practice. We aimed to identify the perceived benefits and harms associated with the use of CP and to explore the potential impact of medicolegal concerns on clinical decision-making. We also sought to ascertain the views of Australian and New Zealand anaesthetists on whether recommendations relating to CP should be included in airway management guidelines. We designed an electronic survey comprised of 15 questions that was emailed to 981 randomly selected Fellows of the Australian and New Zealand College of Anaesthetists (ANZCA) by the ANZCA Clinical Trials Network on behalf of the investigators. We received responses from 348 invitees (response rate 35.5%). Of the 348 respondents, 267 (76.9%) indicated that they would routinely use CP for patients determined to be at increased risk of gastric regurgitation. When asked whether participants believed the use of CP reduces the risk of gastric regurgitation, 39.8% indicated yes, 23.8% believed no and 36.3% were unsure. Of the respondents who indicated that they routinely performed CP, 159/267 (60%) indicated that concerns over the potential medicolegal consequences of omitting CP in a patient who subsequently aspirates was one of the main reasons for using CP. The majority (224/337; 66%) of respondents believed that recommendations about the use of CP in airway management guidelines should include individual practitioner judgement, while only 55/337 (16%) respondents believed that routine CP should be advocated in contemporary emergency airway management guidelines.

"How to Recognize if Your Child Is Seriously Ill" During COVID-19 Lockdown: An Evaluation of Parents' Confidence and Health-Seeking Behaviors.

Background: Parents' health-seeking behaviors has changed during the COVID-19 pandemic. Providing parents with guidance in decision making might improve their confidence to seek timely advice when a child becomes ill. The aim of this study was to evaluate the "How to recognize if your child is seriously ill" leaflet on parents' confidence, health-seeking behaviors, and usefulness during the COVID-19 lockdown. Method: A nine-item survey, codesigned with parent advisors, was used to measure confidence and health-seeking behavior. Social media was used for data collection in a 6-week period (April-June 2020) during COVID-19 lockdown in the United Kingdom. Categorical data were analyzed as frequencies, and inductive content analysis was performed with the qualitative data. Results: In total, 171 parents responded. Most parents (n = 160, 93.6%) found the leaflet helpful. The leaflet increased the confidence among 116 parents (67.8%) to recognize if their child is ill, and 156 (91.2%) parents had a better understanding of when and where to seek help. Thirty-three (19.2%) parents used the leaflet, while their child was unwell during COVID-19 lockdown, and in 14 (42%) cases, the leaflet resulted in changing health-seeking behavior for that episode. Twelve of these parents decided to seek medical consultation when they had not planned to before. Content analysis revealed three categories. (1) Knowledge-parents found the leaflet an objective source to validate their concerns. (2) Usability-parents reported that the leaflet was clearly designed. (3) Decision aid-parents commented that the leaflet provided clarification around recognition of serious symptoms and when and where to seek appropriate care. Conclusions: Our leaflet provided parents with guidance on decision making and risk assessment of ill children during COVID-19 lockdown. Parents found it helpful; it increased their confidence and positively changed their health-seeking behaviors. Providing parents with targeted information to recognize serious illness in children at home could potentially foster self-care and safely maintain a reduction in pediatric emergency attendances for self-limiting illnesses.

Can quantitative MRI be used in the clinical setting to quantify the impact of intra-articular glucocorticoid injection on synovial disease activity in juvenile idiopathic arthritis?

BACKGROUND: Juvenile idiopathic arthritis (JIA), the most common chronic rheumatic disease of childhood, is characterised by synovitis. Clinical assessments of synovitis are imperfect, relying on composite and indirect measures of disease activity including clinician-reported measures, patient-reported measures and blood markers. Contrast-enhanced MRI is a more sensitive synovitis assessment technique but clinical utility is currently limited by availability and inter-observer variation. Improved quantitative MRI techniques may enable future development of more stringent MRI-defined remission criteria. The objective of this study was to determine the utility and feasibility of quantitative MRI measurement of synovial volume and vascularity in JIA before and twelve weeks after intra-articular glucocorticoid injection (IAGI) of the knee and to assess the acceptability of MRI to participating families. METHODS: Children and young people with JIA and a new episode of knee synovitis requiring IAGI were recruited from the Great North Children's Hospital in Newcastle upon Tyne. Quantitative contrast-enhanced MRI was performed prior to and twelve weeks after IAGI, in addition to standard clinical assessment tools, including the three-variable clinical juvenile arthritis disease activity score (cJADAS) and active joint count. RESULTS: Eleven young people (5 male, median age 13 years, range 7-16) with JIA knee flare were recruited and 10 completed follow-up assessment. Following IAGI, the median (interquartile range) cJADAS improved from 8.5 (2.7) to 1.6 (3.9), whilst the median synovial volume improved from 38.5cm3 (82.1cm3) to 0.0cm3 (0.2cm3). Six patients presented with frank synovitis outside normal limits on routine MRI reporting. A further three had baseline MRI reports within normal limits but the quantitative measurements identified measurable synovial uptake. Post-IAGI quantitative measurements highlighted significant improvements in 9 patients. CONCLUSIONS: IAGI led to a marked reduction in synovial volume, with quantitative MRI identifying more patients with an improved synovial volume than routine qualitative clinical reporting. Improvements in cJADAS scores were more variable with the patient/parent global assessment component contributing most to the scores. Further work is indicated, exploring the utility of quantitative MRI in the assessment of less accessible joints and comparing the impact of different treatment modalities.

Peer-assisted learning: filling the gaps in basic science education for preclinical medical students.

In contrast to peer-assisted learning (PAL) in clinical training, there is scant literature on the efficacy of PAL during basic medical sciences teaching for preclinical students. A group of senior medical students aimed to design and deliver clinically oriented small-group tutorials after every module in the preclinical curriculum at a United Kingdom medical school. Twenty tutorials were delivered by senior students throughout the year to first- and second-year students. A baseline questionnaire was delivered to inform the development of the program followed by an end-point questionnaire the next year (n = 122). Quizzes were administered before and after five separate tutorials to assess changes in mean student scores. Additionally, each tutorial was evaluated via a questionnaire for participants (n = 949). All five posttutorial quizzes showed a significant improvement in mean student score (P < 0.05). Questionnaires showed students found the program to be relevant and useful for revision purposes and appreciated how tutorials contextualized basic science to clinical medicine. Students appreciated the interactive nature of the sessions and found receiving personalized feedback about their learning and consolidating information with someone familiar with the material to be useful. With the inclusion of the program, students felt there were now an adequate number of tutorials during the year. In conclusion, this study shows that senior medical students can design and deliver a program that adds value to the mostly lecture-based formal preclinical curriculum. We hope that our study can prompt further work to explore the effect of PAL on the teaching of basic sciences during preclinical studies.