Postoperative Pain Management in children: guidance from the Pain Committee of the European Society for Paediatric Anaesthesiology (ESPA Pain Management Ladder Initiative) Part II.

The ESPA Pain Management Ladder Initiative is a clinical practice advisory based upon expert consensus supported by the current literature to help ensure a basic standard of perioperative pain management for all children. In 2018 the perioperative pain management of six common pediatric surgical procedures was summarised. The current Pain Management Ladder recommendations focus on five more complex pediatric surgical procedures and suggest basic, intermediate, and advanced pain management methods.

Quantification of persulfidation on specific proteins: are we nearly there yet?

Hydrogen sulfide (H2S) played a pivotal role in the early evolution of life on Earth before the predominance of atmospheric oxygen. The legacy of a persistent role for H2S in life's processes recently emerged through its discovery in modern biochemistry as an endogenous cellular signalling modulator involved in numerous biological processes. One major mechanism through which H2S signals is protein cysteine persulfidation, an oxidative post-translational modification.

Adipocyte deletion of the oxygen-sensor PHD2 sustains elevated energy expenditure at thermoneutrality.

Enhancing thermogenic brown adipose tissue (BAT) function is a promising therapeutic strategy for metabolic disease. However, predominantly thermoneutral modern human living conditions deactivate BAT. We demonstrate that selective adipocyte deficiency of the oxygen-sensor HIF-prolyl hydroxylase (PHD2) gene overcomes BAT dormancy at thermoneutrality.

Non-symbolic estimation of big and small ratios with accurate and noisy feedback.

The ratio of two magnitudes can take one of two values depending on the order they are operated on: a 'big' ratio of the larger to smaller magnitude, or a 'small' ratio of the smaller to larger. Although big and small ratio scales have different metric properties and carry divergent predictions for perceptual comparison tasks, no psychophysical studies have directly compared them. Two experiments are reported in which subjects implicitly learned to compare pairs of brightnesses and line lengths by non-symbolic feedback based on the scaled big ratio, small ratio or difference of the magnitudes presented.

ATP-binding cassette family C member 1 constrains metabolic responses to high-fat diet in male mice.

Glucocorticoids modulate glucose homeostasis, acting on metabolically active tissues such as liver, skeletal muscle, and adipose tissue. Intracellular regulation of glucocorticoid action in adipose tissue impacts metabolic responses to obesity. ATP-binding cassette family C member 1 (ABCC1) is a transmembrane glucocorticoid transporter known to limit the accumulation of exogenously administered corticosterone in adipose tissue.

Deletion of Hsd11b1 suppresses caloric restriction-induced bone marrow adiposity in male but not female mice.

Bone marrow adipose tissue (BMAT) comprises >10% of total adipose mass in healthy humans. It increases in diverse conditions, including ageing, obesity, osteoporosis, glucocorticoid therapy, and notably, during caloric restriction (CR). BMAT potentially influences skeletal, metabolic, and immune functions, but the mechanisms of BMAT expansion remain poorly understood.

The paradox of spring: Thyroid and glucocorticoid responses to cold temperatures and food availability in free living Carneddau ponies.

In seasonal environments, maintaining a constant body temperature poses challenges for endotherms. Cold winters at high latitudes, with limited food availability, create opposing demands on metabolism: upregulation preserves body temperature but depletes energy reserves. Examining endocrine profiles, such as thyroid hormone triiodothyronine (T3) and glucocorticoids (GCs), proxies for changes in metabolic rate and acute stressors, offer insights into physiological trade-offs.

Whole genome sequencing of mouse lines divergently selected for fatness (FLI) and leanness (FHI) revealed several genetic variants as candidates for novel obesity genes.

Background: Analysing genomes of animal model organisms is widely used for understanding the genetic basis of complex traits and diseases, such as obesity, for which only a few mouse models exist, however, without their lean counterparts.

Objective: To analyse genetic differences in the unique mouse models of polygenic obesity (Fat line) and leanness (Lean line) originating from the same base population and established by divergent selection over more than 60 generations.

Methods: Genetic variability was analysed using WGS.

Preneoplastic cells switch to Warburg metabolism from their inception exposing multiple vulnerabilities for targeted elimination.

Otto Warburg described tumour cells as displaying enhanced aerobic glycolysis whilst maintaining defective oxidative phosphorylation (OXPHOS) for energy production almost 100 years ago [1, 2]. Since then, the 'Warburg effect' has been widely accepted as a key feature of rapidly proliferating cancer cells [3-5]. What is not clear is how early "Warburg metabolism" initiates in cancer and whether changes in energy metabolism might influence tumour progression ab initio.

Perceptual addition of continuous magnitudes in an 'artificial algebra'.

Although there is substantial evidence for an innate 'number sense' that scaffolds learning about mathematics, whether the underlying representations are based on discrete or continuous perceptual magnitudes has been controversial. Yet the nature of the computations supported by these representations has been neglected in this debate. While basic computation of discrete non-symbolic quantities has been reliably demonstrated in adults, infants, and non-humans, far less consideration has been given to the capacity for computation of continuous perceptual magnitudes.

Thiosulfate sulfurtransferase deficiency promotes oxidative distress and aberrant NRF2 function in the brain.

Thiosulfate sulfurtransferase (TST, EC 2.8.1.

Dynamic Emotion Recognition and Social Inference Ability in Traumatic Brain Injury: An Eye-Tracking Comparison Study.

Emotion recognition and social inference impairments are well-documented features of post-traumatic brain injury (TBI), yet the mechanisms underpinning these are not fully understood. We examined dynamic emotion recognition, social inference abilities, and eye fixation patterns between adults with and without TBI. Eighteen individuals with TBI and 18 matched non-TBI participants were recruited and underwent all three components of The Assessment of Social Inference Test (TASIT).

Large-scale analysis of sheep rumen metagenome profiles captured by reduced representation sequencing reveals individual profiles are influenced by the environment and genetics of the host.

Background: Producing animal protein while reducing the animal's impact on the environment, e.g., through improved feed efficiency and lowered methane emissions, has gained interest in recent years.

The serotonin transporter sustains human brown adipose tissue thermogenesis.

Activation of brown adipose tissue (BAT) in humans is a strategy to treat obesity and metabolic disease. Here we show that the serotonin transporter (SERT), encoded by SLC6A4, prevents serotonin-mediated suppression of human BAT function. RNA sequencing of human primary brown and white adipocytes shows that SLC6A4 is highly expressed in human, but not murine, brown adipocytes and BAT.

The psychological scaffolding of arithmetic.

Where does arithmetic come from, and why are addition and multiplication its fundamental operations? Although we that arithmetic is true, no explanation that meets standards of scientific rigor is available from philosophy, mathematical logic, or the cognitive sciences. We propose a new approach based on the assumption that arithmetic has a biological origin: Many examples of adaptive behavior such as spatial navigation suggest that organisms can perform arithmetic-like operations on represented magnitudes. If so, these operations-nonsymbolic precursors of addition and multiplication-might be optimal due to evolution and thus identifiable according to an appropriate criterion.

Hepatic hydrogen sulfide levels are reduced in mouse model of Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare human disease characterised by accelerated biological ageing. Current treatments are limited, and most patients die before 15 years of age. Hydrogen sulfide (HS) is an important gaseous signalling molecule that it central to multiple cellular homeostasis mechanisms.

Memory reactivation and suppression modulate integration of the semantic features of related memories in hippocampus.

Encoding an event that overlaps with a previous experience may involve reactivating an existing memory and integrating it with new information or suppressing the existing memory to promote formation of a distinct, new representation. We used fMRI during overlapping event encoding to track reactivation and suppression of individual, related memories. We further used a model of semantic knowledge based on Wikipedia to quantify both reactivation of semantic knowledge related to a previous event and formation of integrated memories containing semantic features of both events.

The effects of caloric restriction on adipose tissue and metabolic health are sex- and age-dependent.

Caloric restriction (CR) reduces the risk of age-related diseases in numerous species, including humans. CR's metabolic effects, including decreased adiposity and improved insulin sensitivity, are important for its broader health benefits; however, the extent and basis of sex differences in CR's health benefits are unknown. We found that 30% CR in young (3-month-old) male mice decreased fat mass and improved glucose tolerance and insulin sensitivity, whereas these effects were blunted or absent in young females.

The HAVEN study-hydroxychloroquine in ANCA vasculitis evaluation-a multicentre, randomised, double-blind, placebo-controlled trial: study protocol and statistical analysis plan.

Background: Patients with non-severe ANCA-associated vasculitis (AAV) are often prescribed immunosuppressive medications that are associated with severe side effects and a reduced quality of life. There is an unmet need for safer effective treatments for these patients. Hydroxychloroquine is being explored due to its effect in similar autoimmune conditions such as systemic lupus erythematosus.

Large scale phenotype imputation and in vivo functional validation implicate ADAMTS14 as an adiposity gene.

Obesity remains an unmet global health burden. Detrimental anatomical distribution of body fat is a major driver of obesity-mediated mortality risk and is demonstrably heritable. However, our understanding of the full genetic contribution to human adiposity is incomplete, as few studies measure adiposity directly.

CArdiac and REspiratory adaptive Computed Tomography (CARE-CT): a proof-of-concept digital phantom study.

Current respiratory 4DCT imaging for high-dose rate thoracic radiotherapy treatments are negatively affected by the complex interaction of cardiac and respiratory motion. We propose an imaging method to reduce artifacts caused by thoracic motion, CArdiac and REspiratory adaptive CT (CARE-CT), that monitors respiratory motion and ECG signals in real-time, triggering CT acquisition during combined cardiac and respiratory bins. Using a digital phantom, conventional 4DCT and CARE-CT acquisitions for nineteen patient-measured physiological traces were simulated.

Genome-wide screening for genetic variants in polyadenylation signal (PAS) sites in mouse selection lines for fatness and leanness.

Alternative polyadenylation (APA) determines mRNA stability, localisation, translation and protein function. Several diseases, including obesity, have been linked to APA. Studies have shown that single nucleotide polymorphisms in polyadenylation signals (PAS-SNPs) can influence APA and affect phenotype and disease susceptibility.

Ethnic homophily affects vaccine prioritization strategies.

People are more likely to interact with other people of their ethnicity-a phenomenon known as ethnic homophily. In the United States, people of color are known to hold proportionately more high-contact jobs and are thus more at risk of virus infection. At the same time, these ethnic groups are on average younger than the rest of the population.