Peripheral thickening of the sarcomeres and pointed end elongation of the thin filaments are both promoted by SALS and its formin interaction partners.

During striated muscle development the first periodically repeated units appear in the premyofibrils, consisting of immature sarcomeres that must undergo a substantial growth both in length and width, to reach their final size. Here we report that, beyond its well established role in sarcomere elongation, the Sarcomere length short (SALS) protein is involved in Z-disc formation and peripheral growth of the sarcomeres. Our protein localization data and loss-of-function studies in the Drosophila indirect flight muscle strongly suggest that radial growth of the sarcomeres is initiated at the Z-disc. As to thin filament elongation, we used a powerful nanoscopy approach to reveal that SALS is subject to a major conformational change during sarcomere development, which might be critical to stop pointed end elongation in the adult muscles. In addition, we demonstrate that the roles of SALS in sarcomere elongation and radial growth are both dependent on formin type of actin assembly factors. Unexpectedly, when SALS is present in excess amounts, it promotes the formation of actin aggregates highly resembling the ones described in nemaline myopathy patients. Collectively, these findings helped to shed light on the complex mechanisms of SALS during the coordinated elongation and thickening of the sarcomeres, and resulted in the discovery of a potential nemaline myopathy model, suitable for the identification of genetic and small molecule inhibitors.

The oxoglutarate dehydrogenase complex is involved in myofibril growth and Z-disc assembly in Drosophila.

Myofibrils are long intracellular cables specific to muscles, composed mainly of actin and myosin filaments. The actin and myosin filaments are organized into repeated units called sarcomeres, which form the myofibrils. Muscle contraction is achieved by the simultaneous shortening of sarcomeres, which requires all sarcomeres to be the same size. Muscles have a variety of ways to ensure sarcomere homogeneity. We have previously shown that the controlled oligomerization of Zasp proteins sets the diameter of the myofibril. Here, we looked for Zasp-binding proteins at the Z-disc to identify additional proteins coordinating myofibril growth and assembly. We found that the E1 subunit of the oxoglutarate dehydrogenase complex localizes to both the Z-disc and the mitochondria, and is recruited to the Z-disc by Zasp52. The three subunits of the oxoglutarate dehydrogenase complex are required for myofibril formation. Using super-resolution microscopy, we revealed the overall organization of the complex at the Z-disc. Metabolomics identified an amino acid imbalance affecting protein synthesis as a possible cause of myofibril defects, which is supported by OGDH-dependent localization of ribosomes at the Z-disc.

Maintenance of Behavioral Variation under Predation Risk: Effects on Personality, Plasticity, and Predictability.

AbstractClassic evolutionary theory predicts that predation will shift trait means and erode variance within prey species; however, several studies indicate higher behavioral trait variance and trait integration in high-predation populations. These results come predominately from field-sampled animals comparing low- and high-predation sites and thus cannot isolate the role of predation from other ecological factors, including density effects arising from higher predation. Here, we study the role of predation on behavioral trait (co)variation in experimental populations of guppies (Poecilia reticulata) living with and without a benthic ambush predator (Jaguar cichlid) to better evaluate the role of predation and where density was equalized among replicates twice per year. At 2.5 years after introduction of the predators (∼10 overlapping generations), 40 males were sampled from each of the six replicate populations and extensively assayed for activity rates, water column use, and latency to feed following disturbance. Individual variation was pronounced in both treatments, with substantial individual variation in means, temporal plasticity, and predictability (inverse residual variance). Predators had little effect on mean behavior, although there was some evidence for greater use of the upper water column in predator-exposed fish. There was greater variance among individuals in water column use in predator-exposed fish, and they habituated more quickly over time; individuals higher in the water column fed slower and had a reduced positive correlation with activity, although again this effect was time specific. Predators also affected the integration of personality and plasticity-among-individual variances in water column use increased, and those in activity decreased, through time-which was absent in controls. Our results contrast with the extensive guppy literature showing rapid evolution in trait means, demonstrating either increases or maintenance of behavioral variance under predation.

Behavioural ecology meets oncology: quantifying the recovery of animal behaviour to a transient exposure to a cancer risk factor.

Wildlife is increasingly exposed to sublethal transient cancer risk factors, including mutagenic substances, which activates their anti-cancer defences, promotes tumourigenesis, and may negatively impact populations. Little is known about how exposure to cancer risk factors impacts the behaviour of wildlife. Here, we investigated the effects of a sublethal, short-term exposure to a carcinogen at environmentally relevant concentrations on the activity patterns of wild Girardia tigrina planaria during a two-phase experiment, consisting of a 7-day exposure to cadmium period followed by a 7-day recovery period. To comprehensively explore the effects of the exposure on activity patterns, we employed the double hierarchical generalized linear model framework which explicitly models residual intraindividual variability in addition to the mean and variance of the population. We found that exposed planaria were less active compared to unexposed individuals and were able to recover to pre-exposure activity levels albeit with a reduced variance in activity at the start of the recovery phase. Planaria showing high activity levels were less predictable with larger daily activity variations and higher residual variance. Thus, the shift in behavioural variability induced by an exposure to a cancer risk factor can be quantified using advanced tools from the field of behavioural ecology. This is required to understand how tumourous processes affect the ecology of species.

Testing personality-pace-of-life associations via artificial selection: insights from selected lines of rainbow trout on the context-dependence of correlations.

More than a decade of study since the personality pace-of-life syndrome (POLS) hypotheses were first proposed, there is little support for it within species. Lack of experimental control, insufficient sampling in the face of highly labile behavioural and metabolic traits, and context dependency of trait correlations are suggested as reasons. Here, I argue that artificial selection and/or use of existing selected lines represents a powerful but under-used approach to furthering our understanding of the POLS. To illustrate this potential, I conducted a focussed review of studies that compared the behaviour, metabolism, growth and survival of an artificially selected fast-growing rainbow trout relative to wild unselected strains, under varying food and risk conditions in the laboratory and field. Resting metabolic rate, food intake, and behaviours that enhance feeding but increase energy expenditure (activity, aggression, boldness), were all higher in the fast strain in paired contrasts, under all food and risk conditions, both in the laboratory and the field. Fast-strain fish grew faster in almost every food and risk situation except where food was highly limited (or absent), had higher survival under low or zero predation risk, but had lower survival under high risk. Several other traits rarely considered in POLS studies were also higher in the fast strain, including maximum swimming speed, and hormones (growth hormone (GH), thyroid hormone (T3) and insulin-like growth factor (IGF-1)). I conclude: (i) assumptions and predictions of the POLS hypothesis are well supported, and (ii) context-dependency was largely absent, but when present revealed trade-offs between food acquisition and predation risk. This focused review highlights the potential of artificial selection in testing POLS ideas, and will hopefully motivate further studies using other animals.

Infrared flashing light through the cricothyroid membrane as guidance to awake intubation with a flexible bronchoscope: A randomised cross-over study.

BACKGROUND: In case of distorted airway anatomy, awake intubation with a flexible bronchoscope can be extremely difficult or even impossible. To facilitate this demanding procedure, an infrared flashing light source can be placed on the patient's neck superficial to the cricothyroid membrane. The light travels through the skin and tissue to the trachea, from where it can be registered by the advancing bronchoscope in the pharynx and seen as flashing white light on the monitor. We hypothesised that the application of this technique would allow more proximal and easier identification of the correct pathway to the trachea in patients with severe airway pathology. METHODS: As part of awake intubation, patients underwent insertion of a flexible video bronchoscope via the mouth into the trachea. The procedure was performed twice, in random order in each patient, with and without the aid of the transcutaneous flashing infrared light. All insertions were video recorded to determine at which anatomical landmark within the airway the correct pathway was identified. The videos are accessible via this link: https://airwaymanagement.dk/infrared_comparative. The predefined landmarks were in successive order: oral cavity, oro-pharynx, tip of epiglottis, arytenoid cartilages, false cords, vocal cords and trachea, as well as the spaces between them. RESULTS: Twenty-two patients had a total of 44 awake insertions with the flexible bronchoscope. The median anatomical level, at which correct identification of the trachea was obtained on the monitor, was, past the epiglottis, with the conventional technique, and at the level of the oropharynx, when using the infrared flashing light (p = .005). The time until the flashing light or the vocal cords were seen was 21 (22) S, mean (SD), and 48 (62) S, during the insertion with and without infrared flashing light activated, respectively (p = .005). Endoscopists rated it easier (p = .001) to recognise the entrance to the trachea in the infrared-group. CONCLUSION: During awake intubation of patients with airway pathology, the application of trans-cricothyroid infrared flashing light to guide the insertion of a flexible bronchoscope significantly facilitated the recognition of the pathway into the trachea and the correct advancement of the flexible endoscope. REGISTRATION OF CLINICAL TRIAL: NCT03930550.

Practice of oxygen use in anesthesiology - a survey of the European Society of Anaesthesiology and Intensive Care.

BACKGROUND: Oxygen is one of the most commonly used drugs by anesthesiologists. The World Health Organization (WHO) gave recommendations regarding perioperative oxygen administration, but the practice of oxygen use in anesthesia, critical emergency, and intensive care medicine remains unclear. METHODS: We conducted an online survey among members of the European Society of Anaesthesiology and Intensive Care (ESAIC). The questionnaire consisted of 46 queries appraising the perioperative period, emergency medicine and in the intensive care, knowledge about current recommendations by the WHO, oxygen toxicity, and devices for supplemental oxygen therapy. RESULTS: Seven hundred ninety-eight ESAIC members (2.1% of all ESAIC members) completed the survey. Most respondents were board-certified and worked in hospitals with > 500 beds. The majority affirmed that they do not use specific protocols for oxygen administration. WHO recommendations are unknown to 42% of respondents, known but not followed by 14%, and known and followed by 24% of them. Respondents prefer inspiratory oxygen fraction (FiO2) ≥80% during induction and emergence from anesthesia, but intraoperatively < 60% for maintenance, and higher FiO2 in patients with diseased than non-diseased lungs. Postoperative oxygen therapy is prescribed more commonly according to peripheral oxygen saturation (SpO2), but shortage of devices still limits monitoring. When monitoring is used, SpO2 ≤ 95% is often targeted. In critical emergency medicine, oxygen is used frequently in patients aged ≥80 years, or presenting with respiratory distress, chronic obstructive pulmonary disease, myocardial infarction, and stroke. In the intensive care unit, oxygen is mostly targeted at 96%, especially in patients with pulmonary diseases. CONCLUSIONS: The current practice of perioperative oxygen therapy among respondents does not follow WHO recommendations or current evidence, and access to postoperative monitoring devices impairs the individualization of oxygen therapy. Further research and additional teaching about use of oxygen are necessary.

TRPM2-mediated extracellular Ca2+ entry promotes acinar cell necrosis in biliary acute pancreatitis.

KEY POINTS: Acute biliary pancreatitis is a significant clinical challenge as currently no specific pharmaceutical treatment exists. Intracellular Ca2+ overload, increased reactive oxygen species (ROS) production, mitochondrial damage and intra-acinar digestive enzyme activation caused by bile acids are hallmarks of acute biliary pancreatitis. Transient receptor potential melastatin 2 (TRPM2) is a non-selective cation channel that has recently emerged as an important contributor to oxidative-stress-induced cellular Ca2+ overload across different diseases. We demonstrated that TRPM2 is expressed in the plasma membrane of mouse pancreatic acinar and ductal cells, which can be activated by increased oxidative stress induced by H2 O2 treatment and contributed to bile acid-induced extracellular Ca2+ influx in acinar cells, which promoted acinar cell necrosis in vitro and in vivo. These results suggest that the inhibition of TRPM2 may be a potential treatment option for biliary pancreatitis. ABSTRACT: Acute biliary pancreatitis poses a significant clinical challenge as currently no specific pharmaceutical treatment exists. Disturbed intracellular Ca2+ signalling caused by bile acids is a hallmark of the disease, which induces increased reactive oxygen species (ROS) production, mitochondrial damage, intra-acinar digestive enzyme activation and cell death. Because of this mechanism of action, prevention of toxic cellular Ca2+ overload is a promising therapeutic target. Transient receptor potential melastatin 2 (TRPM2) is a non-selective cation channel that has recently emerged as an important contributor to oxidative-stress-induced cellular Ca2+ overload across different diseases. However, the expression and possible functions of TRPM2 in the exocrine pancreas remain unknown. Here we found that TRPM2 is expressed in the plasma membrane of mouse pancreatic acinar and ductal cells, which can be activated by increased oxidative stress induced by H2 O2 treatment. TRPM2 activity was found to contribute to bile acid-induced extracellular Ca2+ influx in acinar cells, but did not have the same effect in ductal cells. The generation of intracellular ROS in response to bile acids was remarkably higher in pancreatic acinar cells compared to isolated ducts, which can explain the difference between acinar and ductal cells. This activity promoted acinar cell necrosis in vitro independently from mitochondrial damage or mitochondrial fragmentation. In addition, bile-acid-induced experimental pancreatitis was less severe in TRPM2 knockout mice, whereas the lack of TRPM2 had no protective effect in cerulein-induced acute pancreatitis. Our results suggest that the inhibition of TRPM2 may be a potential treatment option for biliary pancreatitis.

Benchmarking against the MOMS Trial: Zurich Results of Open Fetal Surgery for Spina Bifida.

INTRODUCTION: The Management of Myelomeningocele Study, a.k.a. the MOMS trial, was published in 2011 in the New England Journal of Medicine. This prospective randomized controlled trial proved to be a milestone publication that provided definitive evidence that fetal surgery is a novel standard of care for select fetuses with spina bifida aperta (SB). The goal of our study is to assess whether our center can match these benchmark results. MATERIALS AND METHODS: Our study was conducted according to the MOMS protocol using the same inclusion and exclusion criteria and looked at the same outcome parameters that were used in the MOMS trial. Zurich and MOMS results were compared. RESULTS: We enrolled 20 patients between December 2010 and May 2015 all of whom underwent fetal surgery for SB. Among 51 different outcome variables, there were only 3 favorable (multiplicity-adjusted) significant differences (gestational age at birth, hindbrain herniation, and psychomotor development). There were no statistically significant differences regarding any other parameters. CONCLUSION: Our findings confirm that rigorous apprenticeship, training, and comprehensive prospective data collection enable centers like the Zurich Center for Fetal Diagnosis and Therapy to achieve benchmark results for open fetal surgery for myelomeningocele and myeloschisis. These results justify the existence and continuation of our program. Outcome documentation is an essential element of quality management. It is medically and ethically fundamental for fetal medicine and surgery centers offering high-end innovative medical care.

Impact of retrograde transillumination while securing the airway in obese patients undergoing bariatric surgery.

Video laryngoscopy (VL) is a well-established technique used in anaesthetising obese patients who present with higher risks of airway-related difficulties and desaturations due to shorter safe apnoea periods. However, VL has certain limitations and may fail. We present the Infrared Red Intubation System (IRRIS), a new technique facilitating glottis identification in severely obese patients undergoing anaesthesia for bariatric surgery. This single-centre, prospective trial assessed the efficacy of the IRRIS for VL tracheal intubation in 20 severely obese adult patients undergoing elective bariatric surgery under general anaesthesia. We assessed the ability of the IRRIS to differentiate the transilluminated glottis from the oesophagus and laryngeal folds and evaluated the ease of intubation. The average weight in the investigated patient cohort was 145 ± 29 kg, the suprasternal tissue thickness was 12 ± 4 mm. The median IQR [range] larynx recognition time was 10 [2-50] s, which was similar to that of lean patients. The degree of obesity correlated with the duration to achieve optimal laryngoscopic view and complete the intubation procedure. We achieved successful VL insertion on the first attempt in 13 of 20 cases (65%), and on the second attempt in 7 cases (35%), emphasising the increased probability of successful intubation on the first attempt. Tracheal intubation with the IRRIS lasted 50 [IQR 20-100] s. The lowest SpO2 during intubation was 98 [IQR 83-100] %. Addition of IRRIS to VL insertion facilitated the intubation of difficult airways in severely obese patients. IRRIS improves the visualization of the intubation pathway by selectively highlighting the airway entrance and shortens the time to successfully conclude the intubation procedure.

Meta-analytic insights into factors influencing the repeatability of hormone levels in agricultural, ecological, and medical fields.

Interest in individual variation in hormone concentrations is rapidly increasing, particularly with regard to the evolutionary and practical implications. A key aspect of studying individual variation in any labile trait is estimating the degree of within- versus among-individual variation, but at present, we do not have a broad consensus on the extent to which hormone levels are repeatable and what factors might influence repeatability. To address this knowledge gap, we conducted a comprehensive meta-analysis of hormone levels that included 1,132 estimates of repeatability from 368 studies across three fields of study: agriculture, ecology, and medicine. We assessed the influence of sex, age class, sample type, hormone family, type of hormone measure, assay type, number of subjects, number of samples per subject, and sampling interval on repeatability estimates. Overall mean repeatability was 0.58, but estimates differed substantially among study disciplines, being lowest in ecology (0.34), moderate in agriculture (0.52), and relatively high in medicine (0.68). In addition, repeatability decreased slightly as sampling interval increased, and also tended to be higher for peak hormone levels than baseline levels. Overall, hormone levels are moderately repeatable, suggesting that they can potentially be useful indicators of individual variation. However, estimates of repeatability are quite variable among fields, so caution should be used when relying on single samples to assess individual variation.

In search of cerebrospinal fluid biomarkers of fatigue in multiple sclerosis: A proteomics study.

Fatigue in multiple sclerosis is a very common and cumbersome symptom, but its aetiology is poorly understood. Proteomics is increasingly implemented in multiple sclerosis research, but has not yet been used to study the neurobiological basis of fatigue in multiple sclerosis. To identify potential cerebrospinal fluid biomarkers of fatigue in multiple sclerosis, we collected cerebrospinal fluid of 20 patients with multiple sclerosis with fatigue (MS+), 20 patients with multiple sclerosis without fatigue (MS-), and 20 control subjects without multiple sclerosis and without fatigue (HC). We used a shotgun proteomics approach and label-free quantitative proteomics to analyse the protein content in cerebrospinal fluid. Selected proteins with differential abundance were further validated by immunoblotting. Out of 591 detected cerebrospinal fluid proteins, the abundance of nine proteins differed between the three groups, and seven additional proteins differed between MS+ and MS- patients. Using immunoblot or slot-blot techniques, we confirmed decreased levels of protein kinase C-binding protein NELL2, neural cell adhesion molecule L1-like protein, and reelin in MS+ patients. In conclusion, cerebrospinal fluid proteomics may provide insight into the neurobiological basis of fatigue in multiple sclerosis. The proteins identified to be decreased in MS+ are involved in synaptic plasticity and energy homeostasis, and thus appear as plausible biomarkers of this common symptom.

The influence of environmental gradients on individual behaviour: Individual plasticity is consistent across risk and temperature gradients.

The expression of individual behaviour as a function of environmental variation (behavioural plasticity) is recognized as a means for animals to modify their phenotypes in response to changing conditions. Plasticity has been studied extensively in recent years, leading to an accumulation of evidence for behavioural plasticity within natural populations. Despite the recent attention given to studying individual variation in behavioural plasticity, there is still a lack of consensus regarding its causes and constraints. One pressing question related to this is whether individual plasticity carries over across temporal and environmental gradients. That is, are some individuals more plastic (responsive) than others in general? Here, we examined the influence of temporal and environmental gradients on individual behavioural responses in a marine gastropod, Littoraria irrorata. We measured individual boldness repeatedly over time and in response to tidal cycle (high vs. low, an index of risk) and daily temperature fluctuations (known to affect metabolism), in a controlled field experiment. On average, boldness increased from high to low tide and with increasing temperature but decreased marginally over time. Individuals also differed in their responses to variation in tide and temperature, but not over time. Those which were relatively bold at high tide (when predation risk is greater) were similarly bold at low tide, whereas shy individuals became much more "bold" at low tide. Most notably, individuals that were more responsive to tide (and thus risk) were also more responsive to temperature changes, indicating that plasticity was correlated across contexts (r = 0.57) and that bolder individuals were least plastic overall. This study provides a rare and possibly first example of consistency of individual behavioural plasticity across contexts, suggesting underlying physiology as a common mechanism, and raises the possibility of correlational selection on plasticity.

Metabolic Scope as a Proximate Constraint on Individual Behavioral Variation: Effects on Personality, Plasticity, and Predictability.

Behavioral ecologists have hypothesized that among-individual differences in resting metabolic rate (RMR) may predict consistent individual differences in mean values for costly behaviors or for behaviors that affect energy intake rate. This hypothesis has empirical support and presently attracts considerable attention, but, notably, it does not provide predictions for individual differences in (a) behavioral plasticity or (b) unexplained variation (residual variation from mean individual behavior, here termed predictability). We outline how consideration of aerobic maximum metabolic rate (MMR) and particularly aerobic scope (= MMR - RMR) can be used to simultaneously make predictions about mean and among- and within-individual variation in behavior. We predict that while RMR should be proportional to an individual's mean level of sustained behavioral activity (one aspect of its personality), individuals with greater aerobic scope will also have greater scope to express behavioral plasticity and/or greater unpredictability in behavior (=greater residual variation). As a first step toward testing these predictions, we analyze existing activity data from selectively bred lines of mice that differ in both daily activity and aerobic scope. We find that replicate high-scope mice are more active on average and show greater among-individual variation in activity, greater among-individual variation in plasticity, and greater unpredictability. These data provide some tentative first support for our hypothesis, suggesting that further research on this topic would be valuable.

Tocolysis for in utero Surgery: Atosiban Performs Distinctly Better than Magnesium Sulfate.

INTRODUCTION: To compare tocolysis with magnesium sulfate versus atosiban regarding the occurrence of short-term preterm labor and maternal side effects during and after open fetal myelomeningocele (MMC) repair. MATERIAL AND METHODS: A prospective nonrandomized cohort study was performed including 30 fetal MMC cases. The first 15 cases (group 1) received magnesium sulfate according to the MOMS protocol. In the following 15 cases (group 2), magnesium sulfate was substituted by atosiban. Chorioamniotic membrane separation (CMS), premature prelabor rupture of the fetal membranes (PPROM), preterm delivery <3 weeks after fetal MMC repair, and maternal complications due to the tocolytic medication were the major endpoints. RESULTS: In both groups, one CMS but no PPROM was diagnosed <3 weeks after fetal MMC repair. One patient of group 2 delivered <3 weeks after fetal MMC repair because of an intraoperative placental abruption at 25 weeks. All women of group 1 showed an electrolyte imbalance during magnesium sulfate administration. One woman of group 1 developed several episodes of a third-degree atrioventricular block within the first 3 days after fetal surgery. Lethargy was found in all women during magnesium sulfate therapy. No maternal side effects were found under atosiban. DISCUSSION: The use of atosiban resulted in an almost identical short-term uterine outcome without any serious maternal complications as seen when magnesium sulfate was given. Thus, the authors suggest using atosiban instead of magnesium sulfate in the context of open fetal surgery.

Short term general anesthesia for retro-bulbar block in ophthalmic surgery generates no significant hypercapnia.

To assess the impact of short time hypnosis for retro-bulbar anesthesia on ventilation in patients undergoing ophthalmic surgery of the anterior eye chamber. In all patients, a combined continuous transcutaneous carbon dioxide tension (PtcCO2) and partial oxygen saturation (SpO2) measurement was applied in addition to routine monitoring. To enable unconscious application of retro-bulbar anesthesia, intravenous thiopental was given in one to multiple bolus doses. Transient breathing support included chin lift, Esmarch maneuver and manual hand-bag ventilation via face mask. Main endpoints were apnea time, recovery time according to the Richmond Agitation Sedation Scale, as well as SpO2 and PtcCO2 readings at predefined time points. Fifty-two patients with a mean age of 68 ± 13 years were included. Average thiopental dose was 2.7 ± 0.6 mg/kg. In seven (13.5%) patients repeated doses of thiopental were necessary to a total of 3.3 ± 1.1 mg/kg. Except one patient, no severe, significant or clinical relevant hypercapnia or desaturation periods were observed, and the occurring elevation of PtcCO2 values did not correlate with the application of repeated doses of thiopental or the need for the Esmarch maneuver. Higher PtcCO2 values were associated with the presence of hypertension and smoking. Apnea (p < 0.001) and recovery (p = 0.003) time were significantly prolonged in the patients needing the Esmarch maneuver. Short term anesthesia with thiopental in ophthalmic surgery is associated with a mild but not clinically relevant hypercapnia.

[Kidney exchange programmes in Europe. What is the status of Hungary? A summary of the first results of the ENCKEP (European Network for Collaboration on Kidney Exchange Programmes) COST Action]. / Élodonoros vesecsereprogramok Európában. Hol tart Magyarország? Összefoglaló tanulmány az ENCKEP (European Network for Collaboration on Kidney Exchange Programmes) COST Action eddigi eredményei alapján.

Patients with end-stage renal disease may exchange their willing, but incompatible donors among each other in centrally coordinated kidney exchange programmes. The aim of this writing is to summarise the results of the ENCKEP COST Action, and describe the lessons learned with regard to the plans for the Hungarian kidney exchange programme. The ENCKEP COST Action had several workshops since 2016 September, and its first working group conducted two surveys that they summarised in two handbooks; our description is based on these resources. There are already 10 national kidney exchange programmes in Europe, the oldest is in the Netherlands (operating since 2004) and the largest in the United Kingdom, where already more than 700 patients received a kidney through this programme in the last ten years. There are a number of countries with plans to start a kidney exchange programme, and international collaborations are also getting established in several regions. Kidney exchange programmes can significantly increase the opportunities of the kidney patients for getting living donor transplants, but for the successful operation of a kidney exchange programme the organisers have to resolve several medical, logistic, optimisation, ethical and legal issues. Orv Hetil. 2018; 159(46): 1905-1912.

Is behavioural plasticity consistent across different environmental gradients and through time?

Despite accumulating evidence for individual variation in behavioural plasticity, there is currently little understanding of the causes and consequences of this variation. An outstanding question is whether individual reaction norm (RN) slopes are consistent across different environmental variables-that is, whether an individual that is highly responsive to one environmental variable will be equally responsive to a second variable. Another important and related question is whether RNs are themselves consistently expressed through time or whether they are simply state dependent. Here, we quantified individual activity rates of zebrafish in response to independent manipulations of temperature and food availability that were repeated in discrete 'bursts' of sampling through time. Individuals that were thermally responsive were not more responsive to food deprivation, but they did exhibit greater unexplained variation. Individual RN slopes were consistent (repeatable) over time for both temperature (Rslope = 0.92) and food deprivation responses (Rslope = 0.4), as were mean activity rates in the standard environment (Rintercept = 0.83). Despite the high potential lability of behaviour, we have demonstrated consistency of behavioural RN components and identified potential energetic constraints leading to high consistency of thermal RNs and low consistency of food deprivation RNs.

Difficult airway management and training: simulation, communication, and feedback.

PURPOSE OF REVIEW: Successful and sustainable training and learning of the management of difficult and normal airway is essential for all clinically active anesthesiologists. We emphasize the importance of a continuously updated learning and training environment based on actual knowledge, best available equipment, standardized procedures, and educational theory. RECENT FINDINGS: In the past, most of the training were based on 'learning by doing' under the supervision of superiors or experienced colleagues. This has been recognized as insufficient and training has evolved to its recent level by structuring it into technical, methodological, and behavioral components. Additionally, a large part of it has been shifted away from learning on patients to simulated scenarios in designated environments. The contents, structure, components, and succession of components have been refined according to the steadily evolving and available instruments. Increasingly, team interaction and behavioral aspects gained more attention and became part of standardized education units that are tailored to the learners' clinical role and level of experience. SUMMARY: We present the details of the Zurich Airway Training and Simulation program, which has been constantly updated to the actual state of knowledge and available equipment.

Cancer and life-history traits: lessons from host-parasite interactions.

Despite important differences between infectious diseases and cancers, tumour development (neoplasia) can nonetheless be closely compared to infectious disease because of the similarity of their effects on the body. On this basis, we predict that many of the life-history (LH) responses observed in the context of host-parasite interactions should also be relevant in the context of cancer. Parasites are thought to affect LH traits of their hosts because of strong selective pressures like direct and indirect mortality effects favouring, for example, early maturation and reproduction. Cancer can similarly also affect LH traits by imposing direct costs and/or indirectly by triggering plastic adjustments and evolutionary responses. Here, we discuss how and why a LH focus is a potentially productive but under-exploited research direction for cancer research, by focusing our attention on similarities between infectious disease and cancer with respect to their effects on LH traits and their evolution. We raise the possibility that LH adjustments can occur in response to cancer via maternal/paternal effects and that these changes can be heritable to (adaptively) modify the LH traits of their offspring. We conclude that LH adjustments can potentially influence the transgenerational persistence of inherited oncogenic mutations in populations.