The branched-chain amino acid requerement in neonates

Growth during the earliest stages of life is an important determinant of an individual’s later health and risk of chronic disease. Substantial evidence shows that growth in the first 2 years of life, especially high early weight gain, is associated with adverse health outcomes later in life, including increased blood pressure, increased weight gain and body fat deposition and increased risk of diabetes. Higher protein intake for infants who are formula fed may play a role with these health outcomes because formula-fed children reach a higher body weight and weight for length at one year of age compared to those fed breast milk. A lower protein intake in infant formula is associated with lower weight up at 2 years of age which might be beneficial because the slower pattern of growth in breastfed infants might be protective for the development of the metabolic syndrome. In preterm infants, however, a higher protein intake in the first month of life correlates with improved neurodevelopment. Preterm infants have higher protein turnover rates and protein losses than terms and thereby higher protein requirements. Excessive intake of amino acids has been shown to reduce (brain) growth and to influence neurotransmitter concentrations in the brain of rats which might put the developing brain at risk. Inadequate amino acid intake impairs protein synthesis, which is pivotal for growth. The growth rate of the preterm infant should mimic at least the growth rate of the intrauterine fetus at the same gestational age. Achieving appropriate growth and nutrition accretion of preterm neonates is often difficult during hospitalization because of metabolic and gastrointestinal immaturity and other complicating medical conditions. Many preterm neonates require total parental nutrition for their initial nutritional support but this is associated with several complications, including the increased risk of infection, mucosal atrophy and cholestatic jaundice. Therefore, transition to full enteral feeding and the cessation of TPN are accomplished as soon as feasible and safe, taking in consideration that enteral feeding is associated with a detrimental morbidity like necrotising enterocolitis. Enteral nutrition can be initiated immediately after birth by introducing small amounts to enhance the development of the gastro-intestinal tract and for this reason is referred to as “trophic”, “priming” or “minimal enteral feeding”

The SWAP EUV Imaging Telescope Part I: Instrument Overview and Pre-Flight Testing

The Sun Watcher with Active Pixels and Image Processing (SWAP) is an EUV solar telescope on board ESA's Project for Onboard Autonomy 2 (PROBA2) mission launched on 2 November 2009. SWAP has a spectral bandpass centered on 17.4 nm and provides images of the low solar corona over a 54x54 arcmin field-of-view with 3.2 arcsec pixels and an imaging cadence of about two minutes. SWAP is designed to monitor all space-weather-relevant events and features in the low solar corona. Given the limited resources of the PROBA2 microsatellite, the SWAP telescope is designed with various innovative technologies, including an off-axis optical design and a CMOS-APS detector. This article provides reference documentation for users of the SWAP image data.Comment: 26 pages, 9 figures, 1 movi

Acute stress response in children with meningococcal sepsis: important differences in the growth hormone/insulin-like growth factor I axis between nonsurvivors and survivors

Septic shock is the most severe clinical manifestation of meningococcal disease and is predominantly seen in children under 5 yr of age. Very limited research has been performed to elucidate the alterations of the GH/IGF-I axis in critically ill children. We evaluated the GH/IGF-I axis and the levels of IGF-binding proteins (IGFBPs)

On Solving the Coronal Heating Problem

This article assesses the current state of understanding of coronal heating, outlines the key elements of a comprehensive strategy for solving the problem, and warns of obstacles that must be overcome along the way.Comment: Accepted by Solar Physics; Published by Solar Physic

A deep learning system for detection of early Barrett's neoplasia:a model development and validation study

BACKGROUND: Computer-aided detection (CADe) systems could assist endoscopists in detecting early neoplasia in Barrett's oesophagus, which could be difficult to detect in endoscopic images. The aim of this study was to develop, test, and benchmark a CADe system for early neoplasia in Barrett's oesophagus.METHODS: The CADe system was first pretrained with ImageNet followed by domain-specific pretraining with GastroNet. We trained the CADe system on a dataset of 14 046 images (2506 patients) of confirmed Barrett's oesophagus neoplasia and non-dysplastic Barrett's oesophagus from 15 centres. Neoplasia was delineated by 14 Barrett's oesophagus experts for all datasets. We tested the performance of the CADe system on two independent test sets. The all-comers test set comprised 327 (73 patients) non-dysplastic Barrett's oesophagus images, 82 (46 patients) neoplastic images, 180 (66 of the same patients) non-dysplastic Barrett's oesophagus videos, and 71 (45 of the same patients) neoplastic videos. The benchmarking test set comprised 100 (50 patients) neoplastic images, 300 (125 patients) non-dysplastic images, 47 (47 of the same patients) neoplastic videos, and 141 (82 of the same patients) non-dysplastic videos, and was enriched with subtle neoplasia cases. The benchmarking test set was evaluated by 112 endoscopists from six countries (first without CADe and, after 6 weeks, with CADe) and by 28 external international Barrett's oesophagus experts. The primary outcome was the sensitivity of Barrett's neoplasia detection by general endoscopists without CADe assistance versus with CADe assistance on the benchmarking test set. We compared sensitivity using a mixed-effects logistic regression model with conditional odds ratios (ORs; likelihood profile 95% CIs).FINDINGS: Sensitivity for neoplasia detection among endoscopists increased from 74% to 88% with CADe assistance (OR 2·04; 95% CI 1·73-2·42; p&lt;0·0001 for images and from 67% to 79% [2·35; 1·90-2·94; p&lt;0·0001] for video) without compromising specificity (from 89% to 90% [1·07; 0·96-1·19; p=0·20] for images and from 96% to 94% [0·94; 0·79-1·11; ] for video; p=0·46). In the all-comers test set, CADe detected neoplastic lesions in 95% (88-98) of images and 97% (90-99) of videos. In the benchmarking test set, the CADe system was superior to endoscopists in detecting neoplasia (90% vs 74% [OR 3·75; 95% CI 1·93-8·05; p=0·0002] for images and 91% vs 67% [11·68; 3·85-47·53; p&lt;0·0001] for video) and non-inferior to Barrett's oesophagus experts (90% vs 87% [OR 1·74; 95% CI 0·83-3·65] for images and 91% vs 86% [2·94; 0·99-11·40] for video).INTERPRETATION: CADe outperformed endoscopists in detecting Barrett's oesophagus neoplasia and, when used as an assistive tool, it improved their detection rate. CADe detected virtually all neoplasia in a test set of consecutive cases.FUNDING: Olympus.</p

Genome-Scale Metabolic Modeling Elucidates the Role of Proliferative Adaptation in Causing the Warburg Effect

The Warburg effect - a classical hallmark of cancer metabolism - is a counter-intuitive phenomenon in which rapidly proliferating cancer cells resort to inefficient ATP production via glycolysis leading to lactate secretion, instead of relying primarily on more efficient energy production through mitochondrial oxidative phosphorylation, as most normal cells do. The causes for the Warburg effect have remained a subject of considerable controversy since its discovery over 80 years ago, with several competing hypotheses. Here, utilizing a genome-scale human metabolic network model accounting for stoichiometric and enzyme solvent capacity considerations, we show that the Warburg effect is a direct consequence of the metabolic adaptation of cancer cells to increase biomass production rate. The analysis is shown to accurately capture a three phase metabolic behavior that is observed experimentally during oncogenic progression, as well as a prominent characteristic of cancer cells involving their preference for glutamine uptake over other amino acids

Host switching pathogens, infectious outbreaks and zoonosis: A Marie Skłodowska-Curie innovative training network (HONOURs)

The increase of the human population is accompanied by growing numbers of livestock to feed this population, as well as by an increase of human invasion into natural habitats of wild animals. As a result, both animals and humans are becoming progressively vulnerable to infections with known (zoonotic) pathogens, but are also increasingly exposed to novel viruses. Global trade as well as climate changes can contribute to pathogen transmission, e.g. through import of infected vectors or expansion of habitats for arthropod vectors such as mosquitoes and midges. Infectious disease outbreaks, especially those by novel viruses, are generally unexpected, and therefore we should be prepared with tools and abilities for immediate action, including the identification of the causative agent, the evaluation of its pathogenic potential for animals and humans, and the fast development of diagnostic assays to allow contact tracing and quarantine measures. HONOURs is a Marie Skłodowska-Curie Actions Innovative Training Network (MSCA-ITN), teaching 15 talented young researchers to become “preparedness-experts”. HONOURs, initiated in April 2017, involves 11 laboratories from 6 different European countries, all at the forefront of novel virus investigations and characterizations. The network includes surveillance experts in both the veterinary and the human health sector, who have developed and utilize highly sensitive virus discovery techniques, e.g. next generation sequencing based genomics and universal primers based PCR, to allow identification and characterization of novel viruses. Production of pure viral proteins, providing high-resolution structures, aids in the design of novel, fast and easy-to-use diagnostics. Organotypic in vitro cell cultures systems (e.g. pseudostratified human airway epithelia) provide tools for virus replication, if needed via a reverse genetics platform, and the production of virus stocks permits inoculation in animal models to examine disease, evaluate candidate vaccines, and fulfilment of the Koch's postulates. Scientists of the various institutes will provide training in the HONOURs network through specialized courses and workshops, combined with challenging research projects. The final aim of the network is to deliver 15 expert scientists, ready to act in case of the emergence of an epidemic

The creatine kinase system and pleiotropic effects of creatine

The pleiotropic effects of creatine (Cr) are based mostly on the functions of the enzyme creatine kinase (CK) and its high-energy product phosphocreatine (PCr). Multidisciplinary studies have established molecular, cellular, organ and somatic functions of the CK/PCr system, in particular for cells and tissues with high and intermittent energy fluctuations. These studies include tissue-specific expression and subcellular localization of CK isoforms, high-resolution molecular structures and structure–function relationships, transgenic CK abrogation and reverse genetic approaches. Three energy-related physiological principles emerge, namely that the CK/PCr systems functions as (a) an immediately available temporal energy buffer, (b) a spatial energy buffer or intracellular energy transport system (the CK/PCr energy shuttle or circuit) and (c) a metabolic regulator. The CK/PCr energy shuttle connects sites of ATP production (glycolysis and mitochondrial oxidative phosphorylation) with subcellular sites of ATP utilization (ATPases). Thus, diffusion limitations of ADP and ATP are overcome by PCr/Cr shuttling, as most clearly seen in polar cells such as spermatozoa, retina photoreceptor cells and sensory hair bundles of the inner ear. The CK/PCr system relies on the close exchange of substrates and products between CK isoforms and ATP-generating or -consuming processes. Mitochondrial CK in the mitochondrial outer compartment, for example, is tightly coupled to ATP export via adenine nucleotide transporter or carrier (ANT) and thus ATP-synthesis and respiratory chain activity, releasing PCr into the cytosol. This coupling also reduces formation of reactive oxygen species (ROS) and inhibits mitochondrial permeability transition, an early event in apoptosis. Cr itself may also act as a direct and/or indirect anti-oxidant, while PCr can interact with and protect cellular membranes. Collectively, these factors may well explain the beneficial effects of Cr supplementation. The stimulating effects of Cr for muscle and bone growth and maintenance, and especially in neuroprotection, are now recognized and the first clinical studies are underway. Novel socio-economically relevant applications of Cr supplementation are emerging, e.g. for senior people, intensive care units and dialysis patients, who are notoriously Cr-depleted. Also, Cr will likely be beneficial for the healthy development of premature infants, who after separation from the placenta depend on external Cr. Cr supplementation of pregnant and lactating women, as well as of babies and infants are likely to be of benefit for child development. Last but not least, Cr harbours a global ecological potential as an additive for animal feed, replacing meat- and fish meal for animal (poultry and swine) and fish aqua farming. This may help to alleviate human starvation and at the same time prevent over-fishing of oceans

Slow Solar Wind Connection Science during Solar Orbiter’s First Close Perihelion Passage

The Slow Solar Wind Connection Solar Orbiter Observing Plan (Slow Wind SOOP) was developed to utilize the extensive suite of remote-sensing and in situ instruments on board the ESA/NASA Solar Orbiter mission to answer significant outstanding questions regarding the origin and formation of the slow solar wind. The Slow Wind SOOP was designed to link remote-sensing and in situ measurements of slow wind originating at open–closed magnetic field boundaries. The SOOP ran just prior to Solar Orbiter’s first close perihelion passage during two remote-sensing windows (RSW1 and RSW2) between 2022 March 3–6 and 2022 March 17–22, while Solar Orbiter was at respective heliocentric distances of 0.55–0.51 and 0.38–0.34 au from the Sun. Coordinated observation campaigns were also conducted by Hinode and IRIS. The magnetic connectivity tool was used, along with low-latency in situ data and full-disk remote-sensing observations, to guide the target pointing of Solar Orbiter. Solar Orbiter targeted an active region complex during RSW1, the boundary of a coronal hole, and the periphery of a decayed active region during RSW2. Postobservation analysis using the magnetic connectivity tool, along with in situ measurements from MAG and SWA/PAS, showed that slow solar wind originating from two out of three of the target regions arrived at the spacecraft with velocities between ∼210 and 600 km s−1. The Slow Wind SOOP, despite presenting many challenges, was very successful, providing a blueprint for planning future observation campaigns that rely on the magnetic connectivity of Solar Orbiter