Neurodevelopmental outcomes after prenatal exposure to anaesthesia for maternal surgery: a propensity-score weighted bidirectional cohort study.

Up to 1% of pregnant women undergo anaesthesia for non-obstetric surgery. This study investigated neurodevelopmental outcomes after prenatal anaesthesia for maternal surgery. A bidirectional cohort study of children born between 2001 and 2018 was performed: neurodevelopmental outcomes of children who had received prenatal anaesthesia for maternal surgery were prospectively compared with unexposed children, with exposure status being assessed retrospectively. Children exposed to anaesthesia for obstetric and fetal surgery were excluded. The primary outcome was the global executive composite of the behaviour rating inventory of executive function score. Our secondary outcomes were: total problems; internalising problems and externalising problems derived from the child behaviour checklist; psychiatric diagnoses; and learning disorders. In 90% of exposed children, there was a single mean (SD) antenatal anaesthesia exposure lasting 91(94) min. There was a broad spectrum of indications, with abdominal surgery being most frequent. Parents of 129 exposed (response rate 68%) and 453 unexposed (response rate 63%) children participated. There were no arguments for non-response bias. After propensity weighting, there were no statistically significant differences in primary outcome, with a weighted mean difference (95%CI) of exposed minus unexposed children of 1.9 (-0.4-4.2), p = 0.10; or any of the secondary outcomes. Sensitivity analyses confirmed the robustness. Exploratory analyses, however, showed significant differences in certain subgroups for the primary outcome, (e.g. for intra-abdominal surgery, exposure duration > 1 h) and some cognitive subdomains (e.g. working memory and attention). This bidirectional cohort study, the largest investigation on the subject to date, has found no evidence in the general population for an association between prenatal exposure to anaesthesia and impaired neurodevelopmental outcomes.

Fluctuations of a membrane nanotube revealed by high-resolution force measurements.

Pulling membrane nanotubes from liposomes presents a powerful method to gain access to membrane mechanics. Here we extend classical optical tweezers studies to infer membrane nanotube dynamics with high spatial and temporal resolution. We first validate our force measurement setup by accurately measuring the bending modulus of EPC membrane in tube pulling experiments. Then we record the position signal of a trapped bead when it is connected, or not, to a tube. We derive the fluctuation spectrum of these signals and find that the presence of a membrane nanotube induces higher fluctuations, especially at low frequencies (10-1000 Hz). We analyse these spectra by taking into account the peristaltic modes of nanotube fluctuations. This analysis provides a new experimental framework for a quantitative study of the fluctuations of nanotubular membrane structures that are present in living cells, and now classically used for in vitro biomimetic approaches.

Cell-sized liposome doublets reveal active tension build-up driven by acto-myosin dynamics.

Cells modulate their shape to fulfill specific functions, mediated by the cell cortex, a thin actin shell bound to the plasma membrane. Myosin motor activity, together with actin dynamics, contributes to cortical tension. Here, we examine the individual contributions of actin polymerization and myosin activity to tension increase with a non-invasive method. Cell-sized liposome doublets are covered with either a stabilized actin cortex of preformed actin filaments, or a dynamic branched actin network polymerizing at the membrane. The addition of myosin II minifilaments in both cases triggers a change in doublet shape that is unambiguously related to a tension increase. Preformed actin filaments allow us to evaluate the effect of myosin alone while, with dynamic actin cortices, we examine the synergy of actin polymerization and myosin motors in driving shape changes. Our assay paves the way for a quantification of tension changes triggered by various actin-associated proteins in a cell-sized system.

Within-subject variability during spatial working memory in children with ADHD: an event-related potentials study.

Working memory (WM) dysfunction and increased within-subject variability are known issues in attention deficit/hyperactivity disorder (ADHD) patients. Little is known about the electrophysiological characteristics of this variability. We evaluated behavioral and electrophysiological within-subject variability taking developmental aspects into account in a group of ADHD patients. Multichannel (n = 31) event-related potentials (ERP) were measured during a visuo-spatial backmatching task; 44 children (8-16 years old) were tested: 22 children with ADHD, combined (n = 17) and inattentive (n = 5) type, and 22 age- and intelligence-matched control children. One-backmatching (BM1) and two-backmatching (BM2) tasks were performed. Classical behavioral parameters and target and nontarget ERP were compared between groups. In addition, motor response variability and ERP amplitude variability were studied. Age-related changes in both motor response and ERP amplitude variability were analyzed in each group. Attention deficit/hyperactivity disorder children made more commission errors, which was more pronounced in the difficult (BM2) task. No difference between groups was found in ERP amplitude and in motor response variability. However, ADHD patients had higher ERP amplitude variability, which was again more pronounced in the difficult WM task. A delayed maturation of amplitude variability was seen in ADHD patients with a slower than in controls decrease in variability with age. This amplitude variability was correlated with the number of commissions, but in an opposite way for ADHD and control children. Our findings indicate an impaired visuo-spatial WM processing in ADHD children with greater ERP amplitude variability compared to controls. Our results also support the view of a delayed cortical development of visuo-spatial WM circuits in this disorder.

Actin modulates shape and mechanics of tubular membranes.

The actin cytoskeleton shapes cells and also organizes internal membranous compartments. In particular, it interacts with membranes for intracellular transport of material in mammalian cells, yeast, or plant cells. Tubular membrane intermediates, pulled along microtubule tracks, are formed during this process and destabilize into vesicles. While the role of actin in tubule destabilization through scission is suggested, literature also provides examples of actin-mediated stabilization of membranous structures. To directly address this apparent contradiction, we mimic the geometry of tubular intermediates with preformed membrane tubes. The growth of an actin sleeve at the tube surface is monitored spatiotemporally. Depending on network cohesiveness, actin is able to entirely stabilize or locally maintain membrane tubes under pulling. On a single tube, thicker portions correlate with the presence of actin. These structures relax over several minutes and may provide enough time and curvature geometries for other proteins to act on tube stability.

Quality of survival assessment in European childhood brain tumour trials, for children below the age of 5 years.

The highest incidence rate of childhood brain tumours is in children below the age of five years, who are particularly vulnerable to the effects of treatments. The assessment of quality of survival (QoS) in multiple domains is essential to compare the outcomes for different tumour types and treatment regimens. The aim of this position statement is to present the domains of health and functioning to be assessed in children from birth to five years, to advance the collection of a common QoS data set in European brain tumour trials. The QoS group of the European Society of Paediatric Oncology (SIOP-E) Brain Tumour group conducted consensus discussions over a period of six years to establish domains of QoS that should be prioritised in clinical trials involving children under 5 years. The domains of health and functioning that were agreed to affect QoS included: medical outcomes (e.g. vision, hearing, mobility, endocrine), emotion, behaviour, adaptive behaviour, and cognitive functioning. As for children aged five years and older, a 'core plus' approach is suggested in which core assessments are recommended for all clinical trials. The core component for children from birth to three years includes indirect assessment which, in this age-group, requires proxy assessment by a parent, of cognitive, emotional and behaviour variables and both direct and indirect endocrine measures. For children from four years of age direct cognitive assessment is also recommended as 'core'. The 'plus' components enable the addition of assessments which can be selected by individual countries and/or by, age-, treatment-, tumour type- and tumour location-specific trials.

How cellular membrane properties are affected by the actin cytoskeleton.

Lipid membranes define the boundaries of living cells and intracellular compartments. The dynamic remodelling of these membranes by the cytoskeleton, a very dynamic structure made of active biopolymers, is crucial in many biological processes such as motility or division. In this review, we present some aspects of cellular membranes and how they are affected by the presence of the actin cytoskeleton. We show that, in parallel with the direct study of membranes and cytoskeleton in vivo, biomimetic in vitro systems allow reconstitution of biological processes in a controlled environment. In particular, we show that liposomes, or giant unilamellar vesicles, encapsulating a reconstituted actin network polymerizing at their membrane are suitable models of living cells and can be used to decipher the relative contributions of membrane and actin on the mechanical properties of the cellular interface.

Direction of hyphal growth: a relevant parameter in the development of filamentous fungi.

Macroscopic and microscopic measurements of the growth of Trichoderma viride and Rhizopus oligosporus were compared at different values of water activity of the solid medium. The relationship between radial extension rate and hyphal growth rate was found to be dependent on water activity. The observed difference between these two parameters was explained by the distribution of apical directions. The validity of the radial extension rate as a growth criterion could be discussed. The angular distribution of apical axes of growth in the front of the colony was observed at different water activity levels of the solid medium, and a model which links radial growth rate to hyphal growth rate and direction of apex growth was proposed and experimentally validated.

Treatment of Alzheimer's disease: an evaluation of the cholinergic approach.

The cholinergic hypothesis claims that a decrease of acetylcholine (ACh) in the brain of patients with Alzheimer's Disease (AD) plays an important role in the deterioration of cognitive functioning. This hypothesis has led to extensive research in possible therapeutic approaches towards improving cholinergic transmission in AD patients. The different approaches have focused on the following six strategies: ACh precursors, ACh release, M1, M3, or M4 receptor agonists, M2 receptor antagonists, nicotinic agonists, and acetylcholinesterase inhibitors (AChEI). The aim of this review is to assess the effectiveness of the cholinergic approach for the treatment of AD.

[Late postoperative evolution of juvenile arteritis]. / Evolution post-opératoire tardive des artérites juvéniles.

Investigation of 102 patients with arteriopathy and aged under 40 years show two groups as a function of course of disease: inflammatory and stasis arteriopathies. The course of the former disease is practically unaffected by surgery and repair is impossible, the common denominator in this group being amputation. Prognosis is better in patients with high lesions of stasis arteriopathy, but comparison with patients operated upon at "typical" age (58-62 years) showed increased progression of juvenile arteritis as seen by reduced permeability of repair procedures after 5 years. These findings suggest the need for extreme caution before conducting repair operations in this age group, and for maximum use of medical treatment.

Longitudinal study evaluating neuropsychological changes in so-called asymptomatic carriers of the Huntington's disease mutation after 1 year.

OBJECTIVES: To determine (1) whether the battery of neuropsychological tests was sufficiently sensitive to find differences between symptomatic patients with Huntington's disease (HD) and clinically asymptomatic individuals carrying the HD gene (AGC) and individuals without the HD gene (NGC) and (2) whether increasing cognitive impairment is found in AGC as compared with NGC. METHODS: A case-control, single-blind study comparing subjects with clinically manifest HD (n=21), AGC (n=12) or NGC (n=11) and a 1-year follow-up of AGC and NGC. Genotype for the HD gene was determined by molecular testing. A large battery of neuropsychological tests measuring several cognitive domains was performed. RESULTS: On most neuropsychological tasks, HD patients perform significantly worse than AGC and NGC. At baseline and follow-up examination, compared with NGC, AGC had lower scores on the symbol digit modalities test. Scores on a block span task declined more rapidly among AGC than among NGC. CONCLUSION: Cognitive impairments in HD patients are found when compared with clinically asymptomatic individuals carrying the HD mutation. Furthermore, our results suggest that subtle cognitive deficits are present in asymptomatic persons who have inherited the HD gene.

Creatine supplementation in Huntington's disease: a placebo-controlled pilot trial.

OBJECTIVE: To evaluate the effect of creatine (Cr) supplementation (5 g/day) in Huntington's disease (HD). METHODS: A 1-year double-blind placebo-controlled study was performed in 41 patients with HD (stage I through III). At baseline and after 6 and 12 months, the functional, neuromuscular, and cognitive status of the patients was assessed by a test battery that consisted of 1) the Unified Huntington's Disease Rating Scale (UHDRS), 2) an exercise test on an isokinetic dynamometer to assess strength of the elbow flexor muscles, 3) a maximal exercise test on a bicycle ergometer to evaluate cardiorespiratory fitness, and 4) a test to assess bimanual coordination ability. Following the baseline measurements, the subjects were assigned to either a creatine (n = 26) or a placebo group (n = 15). RESULTS: Scores on the functional checklist of the UHDRS (p < 0.05), maximal static torque (p < 0.05), and peak oxygen uptake (p < 0.05) decreased from the start to the end of the study, independent of the treatment received. Cognitive functioning, bimanual coordination ability, and general motor function (total motor scale, UHDRS) did not change from baseline to 1 year in either group. CONCLUSION: One year of Cr intake, at a rate that can improve muscle functional capacity in healthy subjects and patients with neuromuscular disease (5 g/day), did not improve functional, neuromuscular, and cognitive status in patients with stage I to III HD.