Natural killer (NK) cells are lymphocytes with important anti-tumour functions. Cytokine activation of NK cell glycolysis and oxidative phosphorylation (OXPHOS) are essential for robust NK cell responses. However, the mechanisms leading to this metabolic phenotype are unclear. Here we show that the transcription factor cMyc is essential for IL-2/IL-12-induced metabolic and functional responses in mice. cMyc protein levels are acutely regulated by amino acids; cMyc protein is lost rapidly when glutamine is withdrawn or when system l-amino acid transport is blocked. We identify SLC7A5 as the predominant system l-amino acid transporter in activated NK cells. Unlike other lymphocyte subsets, glutaminolysis and the tricarboxylic acid cycle do not sustain OXPHOS in activated NK cells. Glutamine withdrawal, but not the inhibition of glutaminolysis, results in the loss of cMyc protein, reduced cell growth and impaired NK cell responses. These data identify an essential role for amino acid-controlled cMyc for NK cell metabolism and function.

[1] Open fire biomass burning and domestic biofuel burning (e.g., cooking, heating, and charcoal making) algorithms have been incorporated into a terrestrial ecosystem model to estimate CO 2 and key reactive GHGs (CO, NO x , and NMHCs) emissions for the year 2000. The emissions are calculated over the globe at a 0.5°Â 0.5°spatial resolution using tree density imagery, and two separate sets of data each for global area burned and land clearing for croplands, along with biofuel consumption rate data. The estimated global and annual total dry matter (DM) burned due to open fire biomass burning ranges between 5221 and 7346 Tg DM/yr, whereas the resultant emissions ranges are 6564-9093 Tg CO 2 /yr, 438-568 Tg CO/yr, 11-16 Tg NO x /yr (as NO), and 29-40 Tg NMHCs/yr. The results indicate that land use changes for cropland is one of the major sources of biomass burning, which amounts to 25-27% (CO 2 ), 25 -28% (CO), 20-23% (NO), and 28-30% (NMHCs) of the total open fire biomass burning emissions of these gases. Estimated DM burned associated with domestic biofuel burning is 3,114 Tg DM/yr, and resultant emissions are 4825 Tg CO 2 /yr, 243 Tg CO/yr, 3 Tg NO x /yr, and 23 Tg NMHCs/yr. Total emissions from biomass burning are highest in tropical regions (Asia, America, and Africa), where we identify important contributions from primary forest cutting for croplands and domestic biofuel burning.

Purpose Investigate the effect of age category (1–9 years vs 10–18 years), sex, Gross Motor Function Classification System (GMFCS) level, and presence of dystonia on changes in eight function test parameters 24 months after selective dorsal rhizotomy (SDR). Methods Prospective, single-center study of all children aged 3–18 years with bilateral cerebral palsy with spasticity who underwent SDR at a tertiary pediatric neurosurgery center between 2012 and 2019. A linear mixed effects model was used to assess longitudinal changes. Results From 2012 to 2019, 42 children had follow-up available at 24 months. Mean GMFM-66 scores increased after SDR (mean difference 5.1 units: 95% CI 3.05–7.13, p < 0.001). Statistically significant improvements were observed in CPQoL, PEDI Self-care and Mobility, 6MWT, Gillette, and MAS scores. There was no significant difference in the improvements seen for age category, sex, GMFCS level, and presence of dystonia for most of the parameters tested (5/8, 6/8, 5/8, and 6/8 respectively). Conclusion SDR may improve gross and fine motor function, mobility and self-care, quality of life, and overall outcome based on extensive scoring parameter testing at 24 months. Atypical patient populations may benefit from SDR if appropriately selected. Multi-center, prospective registries investigating the effect of SDR are required.

Non-alcoholic fatty liver disease (NAFLD) is associated with overweight/obesity, metabolic syndrome and type 2 diabetes (T2D) due to chronic caloric excess and physical inactivity. Previous meta-analyses have confirmed associations between ultra-processed food (UPF) intake and obesity and T2D. We aim to ascertain the contribution of UPF consumption to the risk of developing NAFLD. We performed a systematic review and meta-analysis (PROSPERO (CRD42022368763)). All records registered on Ovid Medline and Web of Science were searched from inception until December 2022. Studies that assessed UPF consumption in adults, determined according to the NOVA food classification system, and that reported NAFLD determined by surrogate (steatosis) scores, imaging or liver biopsy were included. The association between UPF consumption and NAFLD was assessed using random-effects meta-analysis methods. Study quality was assessed, and evidence credibility evaluated, using the Newcastle Ottawa Scale and NutriGrade systems, respectively. A total of 5454 records were screened, and 112 records underwent full text review. From these, 9 studies (3 cross-sectional, 3 case-control and 3 cohort), analysing 60,961 individuals, were included in the current review. Both moderate (vs. low) (pooled relative risk 1.03 (1.00–1.07) (p = 0.04) (I2 = 0%)) and high (vs. low) (1.42 (1.16–1.75) (<0.01) (I2 = 89%)) intake of UPF significantly increased the risk of NAFLD. Funnel plots demonstrate low risk of publication bias. Consumption of UPF is associated with NAFLD with a dose–response effect. Public health measures to reduce overconsumption of UPF are imperative to reduce the burden of NAFLD, and the related conditions, obesity and T2D.

Abstract Background:Currently, we can only speculate on what the effects of the COVID-19 pandemic have been on medical students and interim foundation year doctors. In order to support them appropriately both now and, in the future, it is imperative that we understand the impact it has had upon them. This study assessed the effects of the COVID-19 pandemic on medical students and interim foundation year doctors across the United Kingdom (UK), and the support that they received and sought. Methods:A prospective, observational, multicentre study was conducted. All medical students and interim foundation year doctors were eligible to participate. The data analysis was carried out as detailed a priori in the protocol. Findings:A total of 2075 individuals participated in the SPICE-19 survey from 33 medical schools. There was a significant (p < 0.0001) decrease in participants’ mood when comparing their mood before the pandemic to during the pandemic. Social distancing and more time at home/with family were the factors that negatively and positively respectively impacted the mood of the greatest number of participants. All areas of life included in the survey were found to have been significantly more negatively impacted than positively impacted (p < 0.0001). 931 participants wanted more support from their university. Participants were mainly seeking support with exam preparation, course material, and financial guidance. Discussion:Medical and foundation schools need to prepare adequate and effective support. If no action is taken, there may be a knock-on effect on workforce planning and the health of our future workforce. When medical students return to their universities, there is likely to be need for enhanced wellbeing support, adaptations in the short-term and long-term strategies for medical education, and provision of financial guidance.