Eggs of the mosquito Aedes aegypti survive desiccation by rewiring their polyamine and lipid metabolism.

Upon water loss, some organisms pause their life cycles and escape death. While widespread in microbes, this is less common in animals. Aedes mosquitoes are vectors for viral diseases. Aedes eggs can survive dry environments, but molecular and cellular principles enabling egg survival through desiccation remain unknown. In this report, we find that Aedes aegypti eggs, in contrast to Anopheles stephensi, survive desiccation by acquiring desiccation tolerance at a late developmental stage. We uncover unique proteome and metabolic state changes in Aedes embryos during desiccation that reflect reduced central carbon metabolism, rewiring towards polyamine production, and enhanced lipid utilisation for energy and polyamine synthesis. Using inhibitors targeting these processes in blood-fed mosquitoes that lay eggs, we infer a two-step process of desiccation tolerance in Aedes eggs. The metabolic rewiring towards lipid breakdown and dependent polyamine accumulation confers resistance to desiccation. Furthermore, rapid lipid breakdown is required to fuel energetic requirements upon water reentry to enable larval hatching and survival upon rehydration. This study is fundamental to understanding Aedes embryo survival and in controlling the spread of these mosquitoes.

WAFER trial: a study protocol for a feasibility randomised controlled trial comparing wide-awake local anaesthesia no tourniquet (WALANT) to general and regional anaesthesia with tourniquet for flexor tendon repair.

INTRODUCTION: Flexor tendons are traditionally repaired under either general anaesthesia (GA) or regional anaesthesia (RA), allowing for the use of an arm tourniquet to minimise blood loss and establish a bloodless surgical field. However, the use of tourniquets exposes the patient to certain risks, including skin, muscle and nerve injuries. A recent advancement in anaesthesia delivery involves the use of a wide-awake approach where no sedation nor tourniquets are used (wide-awake local anaesthesia no tourniquet (WALANT)). WALANT uses local anaesthetic with epinephrine to provide pain relief and vasoconstriction, reducing operative bleeding. Several studies revealed potential benefits for WALANT compared with GA or RA. However, there remains a paucity of high-quality evidence to support the use of WALANT. As a result of this uncertainty, the clinical practice varies considerably. We aim to evaluate the feasibility of WALANT as an alternative to GA and RA in patients undergoing surgical repair of flexor tendon injuries. This involves addressing factors such as clinician and patient support for a trial, clinical equipoise, trial recruitment and dropout and the most relevant outcomes measures for a future definitive trial. METHODS AND ANALYSIS: WAFER is a multicentre, single-blinded, parallel group, randomised controlled trial (RCT) to assess the feasibility of WALANT versus RA and GA. The target population is patients with acute traumatic flexor tendon injuries, across 3 major hand surgery units in England involving a total of 60 participants. Outcome assessors will be blinded. The primary outcome will be the ability to recruit patients into the trial, while secondary outcomes include difference in functional outcome, patient-reported outcome measures, health-related quality of life, cost-effectiveness and complication rates. ETHICS AND DISSEMINATION: Ethical approval was obtained from the London-City and East Research Ethics Committee (22/PR/1197). Findings will be disseminated through peer-reviewed publication, conferences, patient information websites and social media networks. TRIAL REGISTRATION NUMBER: ISRCTN identifier: 15052559.

Appetite for more exchange, connection and collaboration among senior health professionals.

BACKGROUND: The COVID-19 pandemic has highlighted the value of global exchange around knowledge, skills and attitudes among senior healthcare professionals (SHPs). It has also revealed the need for strong peer-led networks and mentorship to tackle the high levels of burnout and 'brain-drain' already plaguing the National Health Service (NHS). We designed a survey to gauge the appetite for exchange programmes among SHPs. METHODS: Data collection was carried out via an online qualitative survey generated by SurveyMonkey software and analysed by three independent authors. RESULTS: 155 responses were collected of which 87.7% were pre-COVID-19 pandemic. 74.2% had ideas to improve healthcare but could not take it forward. 86.6% felt frustrated/down-heartened about work. 74.3% wanted more sharing of teaching resources. 74.2% expressed interest in sabbatical programmes. CONCLUSION: Our survey confirms the desire for more connection, collaboration and exchange among SHPs who are at high risk of burnout, silo-working and leaving the profession early. Sabbaticals have been used successfully in other industries, especially academia, for many years and show long-term investment and value from employers in their employees. Almost 75% of the SHPs in this survey were interested in this but logistics precluded easy access to them. HealthProMatch (HPM) is a platform where SHPs can connect, collaborate and arrange exchanges/sabbaticals with logistical ease. It focuses on bringing leadership, mentorship and quality improvement back home. HPM will pilot in the NHS within anaesthesia and hopes to increase job satisfaction and retention in this precious workforce group.

Progression of coronary calcification in healthy postmenopausal women.

BACKGROUND: Coronary artery calcium score incrementally improves coronary risk prediction beyond that provided by conventional risk factors. Limited information is available regarding rates of progression of coronary calcification in women, particularly those with baseline scores above zero. Further, determinants of progression of coronary artery calcification in women are not well understood. This study prospectively evaluated rates and determinants of progression of coronary artery calcium score in a group of healthy postmenopausal women. METHODS: We determined coronary calcium score by computed tomography and recorded demographic, lifestyle and health characteristics of 914 postmenopausal women, a subset of those enrolled in the Women's Health Initiative Observational Study. The 305 women with calcium score >or=10 Agatston units at baseline were invited for repeat scan. This analysis includes the 94 women who underwent second scans. RESULTS: Mean age of study participants was 65 +/- 9 years (mean +/- SD), body mass index was 26.1 +/- 6.1 kg/m2, and baseline calcium score was 162 +/- 220 Agatston units. Mean interval between scans was 3.3 +/- 0.7 years. A wide range of changes in coronary calcium score was observed, from -53 to +452 Agatston units/year. Women with lower scores at baseline had smaller annual increases in absolute calcium score. Coronary calcium scores increased 11, 31 and 79 Agatston units/year among women with baseline calcium score in the lowest, middle and highest tertiles. In multivariate analysis, age was not an independent predictor of absolute change in coronary calcium score. Hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) use at baseline was a negative predictor (p = 0.015), whereas baseline calcium score was a strong, positive predictor (p < 0.0001) of progression of coronary calcification. CONCLUSION: Among postmenopausal women with coronary calcium score >or= 10 Agatston units, rates of change of coronary calcium score varied widely. In multivariate analysis, statin use was a negative independent determinant, whereas baseline calcium score was a strong positive predictor of annual change in coronary calcium score.