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Over decades, persistent organic pollutants (POPs) and trace metals like mercury (Hg) have reached the remotest areas of the world such as Antarctica by atmospheric transport. Once deposited in polar areas, low temperatures, and limited solar radiation lead to long environmental residence times, allowing the toxic substances to accumulate in biota. We investigated the load of polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDTs) and metabolites (DDEs, DDDs) in embryos from failed eggs of the smallest seabird breeding in Antarctica, the Wilson's storm-petrel (Oceanites oceanicus) at King George Island (Isla 25 de Mayo). We compared samples of different developmental stages collected in 2001, 2003, and 2014 to 2016 to investigate changes in pollutant concentrations over time. We detected eight PCBs including the dioxin-like (dl) congeners PCB 105 and 118 (ΣPCBs: 59-3403 ng g−1 ww) as well as 4,4’-DDE, and 4,4’-DDD (ΣDDX: 19-1035 ng g−1 ww) in the embryos. Samples from the years 2001 and 2003 showed higher concentrations of PCBs than those from 2014 to 2016. Concentrations of DDX was similar in both time intervals. Furthermore, we determined Hg concentrations in egg membranes from 1998 to 2003, and 2014 to 2016. Similar to PCBs, Hg in egg membranes were higher in 1998 than in 2003, and higher in 2003 than in the years 2014 to 2016, suggesting a slow recovery of the pelagic Antarctic environment from the detected legacy pollutants. Embryos showed an increase in pollutant concentrations within the last third of their development. This finding indicates that contaminant concentrations may differ among developmental stages, and it should be taken into account in analyses on toxic impact during embryogenesis.

Full details on the design, strategies and tactics for development of a novel synthetic sequence to farnesyl lipid I and II analogs is reported. The modular route was based on a three coupling strategy involving an efficient solid phase synthesis of the elaborate peptide fragment, which proceeded with excellent yield and stereoselectivity and was efficiently applied for the convergent synthesis of 3-lipid I and II. Furthermore, the generality of this route was demonstrated by synthesis of 3-lipid I congeners that are characteristic for

Made available in DSpace on 2022-04-29T08:37:58Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Background: The possibility of accurately and continuously measuring arterial oxygen partial pressure (PaO2) in horses may facilitate the management of hypoxaemia during general anaesthesia. Objectives: The aim of this study was to evaluate the ability of a novel fibreoptic sensor to measure PaO2 (PaO2Sensor) continuously and in real time in horses undergoing ventilatory manoeuvres during general anaesthesia. Study design: In vivo experimental study. Methods: Six adult healthy horses were anaesthetised and mechanically ventilated in dorsal recumbency. A fibreoptic sensor was placed in one of the facial arteries through a catheter to continuously measure and record PaO2Sensor. After an alveolar recruitment manoeuvre, a decremental positive end-expiratory pressure (PEEP) titration using 20-minute steps of 5 cm H2O from 20 to 0 cm H2O was performed. An arterial blood sample was collected at 15 minutes of ventilation at each PEEP level for PaO2 measurement using an automated blood gas machine (PaO2Ref). The agreement between PaO2Sensor and PaO2Ref was assessed by Pearson's correlation, Bland-Altman plot and four-quadrant plot analysis. In the last minute of ventilation at each PEEP level, a slow tidal inflation/deflation manoeuvre was performed. Results: The mean relative bias between PaO2Sensor and PaO2Ref was 4% with limits of agreement between −17% and 29%. The correlation coefficient between PaO2Sensor and PaO2Ref was 0.98 (P

The Antarctic and the surrounding Southern Ocean are currently subject to rapid environmental changes and increasing anthropogenic impacts. Seabird populations often reflect those changes and so act as indicators of environmental variability. Their population trends may provide information on a variety of environmental parameters on the scale of years or decades. We therefore provide long-term data on the cape petrel (Daption capense) population from a long-term monitoring program on Fildes Peninsula, South Shetland Islands, Maritime Antarctic, an area of considerable human activity. Our data, covering a period of 36 years, indicate some variability, but no clear trend in the number of breeding pairs between the breeding seasons 1985 and 2006. However, beginning in the 2008 season, the population decreased significantly and reached a minimum in the 2020 season. The mean annual decrease between 2008 and 2020 was 10.6%. We discuss possible causes of this strong negative population trend. Anthropogenic disturbance only affects a few breeding sites in the area and is therefore unable, on its own, to explain the consistent population decline at all the breeding sites studied. We think it more likely that reduced food availability was the main cause of the drastic decline in the cape petrel population.

Objectives To compare pulmonary gas exchange, tissue oxygenation and cardiovascular effects of four levels of end-expiratory pressure: no positive end-expiratory pressure (ZEEP), positive end-expiratory pressure (PEEP) of maximal respiratory system compliance (PEEPmaxCrs), PEEPmaxCrs + 2 cmH2O (PEEPmaxCrs+2), PEEPmaxCrs + 4 cmH2O (PEEPmaxCrs+4), in isoflurane-anesthetized dogs. Study design Prospective randomized crossover study. Animals A total of seven healthy male Beagle dogs, aged 1 year and weighing 10.2 ± 0.7 kg (mean ± standard deviation). Methods The dogs were administered acepromazine and anesthesia was induced with propofol and maintained with isoflurane. Ventilation was controlled for 4 hours with ZEEP, PEEPmaxCrs, PEEPmaxCrs+2 or PEEPmaxCrs+4. Cardiovascular, pulmonary gas exchange and tissue oxygenation data were evaluated at 5, 60, 120, 180 and 240 minutes of ventilation and compared using a mixed-model anova followed by Bonferroni test. p Results Cardiac index (CI) and mean arterial pressure (MAP) were lower in all PEEP treatments at 5 minutes when compared with ZEEP. CI persisted lower throughout the 4 hours only in PEEPmaxCrs+4 with the lowest CI at 5 minutes (2.15 ± 0.70 versus 3.45 ± 0.94 L minute–1 m–2). At 180 and 240 minutes, MAP was lower in PEEPmaxCrs+4 than in PEEPmaxCrs, with the lowest value at 180 minutes (58 ± 7 versus 67 ± 7 mmHg). Oxygen delivery index (DO2I) was lower in PEEPmaxCrs+4 than in ZEEP at 5, 60, 120 and 180 minutes. Venous admixture was not different among treatments. Conclusion and clinical relevance The use of PEEP caused a transient decrease in MAP and CI in lung-healthy dogs anesthetized with isoflurane, which improved after 60 minutes of ventilation in all levels of PEEP except PEEPmaxCrs+4. A clinically significant improvement in arterial oxygenation and DO2I was not observed with PEEPmaxCrs and PEEPmaxCrs+2 in comparison with ZEEP, whereas PEEPmaxCrs+4 decreased DO2I.

Im Gesamtmarkt der FMCG-Branche ist der Handelsmarkenanteil im vergangenen Jahr auf 40,2 Prozent angewachsen, wie die Marktforscher von NielsenIQ ermittelt haben. Die Verbrauchermärkte steigerten ihre Marktbedeutung, die Discounter dominieren dennoch weiterhin.

RNA molecules and their expression dynamics play essential roles in the establishment of complex cellular phenotypes and/or in the rapid cellular adaption to environmental changes. Accordingly, analyzing RNA expression remains an important step to understand the molecular basis controlling the formation of cellular phenotypes, cellular homeostasis or disease progression. Steady-state RNA levels in the cells are controlled by the sum of highly dynamic molecular processes contributing to RNA expression and can be classified in transcription, maturation and degradation. The main goal of analyzing RNA dynamics is to disentangle the individual contribution of these molecular processes to the life cycle of a given RNA under different physiological conditions. In the recent years, the use of nonradioactive nucleotide/nucleoside analogs and improved chemistry, in combination with time-dependent and high-throughput analysis, have greatly expanded our understanding of RNA metabolism across various cell types, organisms, and growth conditions.In this chapter, we describe a step-by-step protocol allowing pulse labeling of RNA with the nonradioactive nucleotide analog, 4-thiouracil, in the eukaryotic model organism Saccharomyces cerevisiae and the model archaeon Haloferax volcanii.

The enantioselectivity of the pharmacokinetics of methadone was investigated in anesthetized Shetland ponies after a single intravenous (0.5 mg/kg methadone hydrochloride; n = 6) or constant rate infusion (0.25 mg/kg bolus followed by 0.25 mg/kg/h methadone hydrochloride; n = 3) administration of racemic methadone. Plasma concentrations of l‐methadone and d‐methadone and their major metabolites, l‐ and d‐2‐ethylidene‐1,5‐dimethyl‐3,3‐diphenylpyrrolidine (EDDP), respectively, were analyzed by CE with highly sulfated γ‐cyclodextrin as chiral selector and electrokinetic analyte injection from liquid/liquid extracts prepared at alkaline pH. In both trials, the d‐methadone concentrations were lower than those of l‐methadone and the d‐EDDP levels were lower than those of L‐EDDP. For the case of a single intravenous bolus injection, the plasma concentration versus time profile of methadone enantiomers was analyzed with a two‐compartment pharmacokinetic model. l‐methadone showed a slower elimination rate constant, a lower body clearance, and a smaller steady‐state volume of distribution than d‐methadone. d‐methadone and d‐EDDP were eliminated faster than their respective l‐enantiomers. This is the first study that outlines that the disposition of racemic methadone administered to anesthetized equines is enantioselective.

Simple Summary In anaesthetized horses, blood oxygenation impairment often occurs. This systematic review compared the effects of low and high inspired oxygen fractions on the arterial oxygen tension and other pulmonary gas exchange parameters in horses during inhalation anaesthesia. Five studies, four experimental and one clinical, were deemed suitable for inclusion. A meta-analysis was performed on the four experimental studies. The oxygen partial pressure was significantly lower with a lower inspired oxygen fraction. However, indices of pulmonary gas exchange were significantly worsened. It is concluded that, while only a limited number of studies are available, the use of a higher inspired oxygen fraction in horses during inhalation anaesthesia will result in higher levels of oxygen in the blood; it will also worsen the lung gas exchange status. Further studies are needed to increase the level of evidence on this subject. In anaesthetized horses, pronounced ventilation/perfusion mismatching often occurs. Several authors have investigated the effect of lower inspired oxygen fractions (FiO(2)) to reduce formation of absorption atelectasis. This systematic review compared the effects of low (0.8) FiO(2) on the arterial oxygen tension (PaO2), the alveolar-to-arterial oxygen tension difference (P(A-a)O-2), and the PaO2/FiO(2) ratio in horses during inhalation anaesthesia. Using the Systematic Review Protocol for Animal Intervention Studies, four experimental and one clinical investigations were deemed suitable for inclusion. A meta-analysis was performed on the four experimental studies. The PaO2 was significantly lower (p = 0.0007, mean difference -23.54 kPa, 95% CI -37.18, -9.90) with a lower FiO(2). However, the P(A-a)O-2 was also significantly lower (p < 0.00001, mean difference -20.80 kPa, 95% CI -26.28, -15.32) when using a low FiO(2). For the PaO2/FiO(2) ratio, only one study fitted the inclusion criteria, so no meta-analysis was performed. It is concluded that, while only a limited number of studies are available, the use of a higher FiO(2) in horses during inhalation anaesthesia will result in higher levels of PaO2, but also a larger P(A-a)O-2 difference. Further studies are needed to increase the level of evidence on this subject.

Objective To evaluate the influence of reservoir bag types, volumes and previous use on the peak pressures (Pmax) and the times to develop 30 cmH2O pressure (P30) within a nonrebreathing system with a closed adjustable pressure-limiting (APL) valve. Study design In vitro study using three-way factorial design with repeated measure on one factor. Subjects A total of 75 new anesthesia reservoir bags (five types, three volumes, five bags from each type × volume). The bag types were reusable latex (RL), disposable latex (DL) and three disposable neoprene (DN-1, DN-2 and DN-3). Methods Each bag was tested three times (treatments): new, after prestretching and 1 week later. The bags were attached to a Bain system and anesthesia machine with closed APL valve and patient port with O2 flow 2 L minute–1 until Pmax was reached. The Pmax and time to reach P30 values were determined from recorded pressure traces. General linear mixed model analysis was used to examine the effects of bag type, volume and treatment. One-sided 95% upper prediction limits of Pmax were calculated to test the null hypothesis that predicted Pmax of new bags would be ≥ 50 cmH2O for each factor combination. Results RL bags were the least and DN-3 bags were the most compliant. Prestretching increased compliance in all bag types. Smaller bags of RL, DL and DN-1 were less compliant than larger ones. The predicted Pmax values were Conclusions and clinical relevance To minimize the risk of barotrauma, highly compliant reservoir bags (e.g. DN-3) are recommended and reusable bags should be avoided. Bags should be prestretched before first use, 0.5 L bags should be avoided and fresh gas flow minimized.

Antarctica with its unique conditions for soil development offers the opportunity to disclose basic soil biogeochemical processes in an environment with a low degree of ecosystem interactions. The region’s climate is divided by the mountain ridge of the Antarctic Peninsula: on the South Shetland Islands (King George Island (KGI)) in the west a maritime cold climate prevails, while James Ross Island (JRI) in the east faces the continental cold climate of a polar desert with less precipitation and distinctly more pronounced temperature variations throughout the year. In addition, the autochthonous vegetation differs; while it solely consists of cryptogams on JRI, on KGI two vascular plants (Dechampsia antarctica, Colobanthus quitensis) are endemic. This scarce vegetation patterns together with land surfaces ice-free for several millenia allows studying the complex interaction between soil organic matter (SOM) sequestration and soil structure development with respect to the varying presence and growth of vegetation. The main aim of our study is to decode the mechanisms determining the fate of SOM in maritime Antarctica and to understand how the scarce vegetation drives the chemical composition and distribution of SOM within specific physical SOM fractions. Therefore, we sampled transects ranging from vegetated patches to plant-free soil surfaces. The distance to these vegetation patches was reflected in clear variations in the distribution of carbon and nitrogen and in a decrease in labile SOM constituents as revealed by 13C-CPMAS NMR spectroscopy, while clay-sized mineral-associated SOM dominated the carbon storage throughout all sites. The ongoing climate change is assumed to significantly alter the vegetation distribution and thus drive the storage and composition of SOM. In the future, this will also strongly affect soil microbial activity and land-ocean transitions in Antarctica.

The global prevalence of diabetes mellitus and other metabolic diseases is rapidly increasing. Animal models play pivotal roles in unravelling disease mechanisms and developing and testing therapeutic strategies. Rodents are the most widely used animal models but may have limitations in their resemblance to human disease mechanisms and phenotypes. Findings in rodent models are consequently often difficult to extrapolate to human clinical trials. To overcome this ‘translational gap’, we and other groups are developing porcine disease models. Pigs share many anatomical and physiological traits with humans and thus hold great promise as translational animal models. Importantly, the toolbox for genetic engineering of pigs is rapidly expanding. Human disease mechanisms and targets can therefore be reproduced in pigs on a molecular level, resulting in precise and predictive porcine (PPP) models. In this short review, we summarize our work on the development of genetically (pre)diabetic pig models and how they have been used to study disease mechanisms and test therapeutic strategies. This includes the generation of reporter pigs for studying beta-cell maturation and physiology. Furthermore, genetically engineered pigs are promising donors of pancreatic islets for xenotransplantation. In summary, genetically tailored pig models have become an important link in the chain of translational diabetes and metabolic research.

Im Gegensatz zu Markenartikeln schafften es Handelsmarken 2021 nicht, an das starke Corona-Vorjahr anzuknüpfen: Sie verloren rund 1,6 Mrd. Euro beziehungsweise 2,7 Prozent an Umsatz. Somit gab der Eigenmarkenanteil von 39,4 Prozent im Vorjahr auf 38,5 Prozent nach, wie Nielsen IQ ermittelt hat.

In the present paper, we compare how the kelp gull, Larus dominicanus, utilizes various nest building materials, particularly vascular plants, bryophytes, lichens and other components, in the Fildes Peninsula area (King George Island) and on the Argentine Islands area. In both areas, nest material primarily consisted of the Antarctic hairgrass (Deschampsia antarctica), bryophytes, lichens, feathers, limpets, and algae. Our study reveals area-specific differences in the utilization of plants for nest building related to local conditions during the nesting season. In the Fildes area, vegetation emerges from under the winter snow cover earlier in the spring, giving the gulls greater choice locally, meaning that the gulls need not resort to long distance material transfer. Here, mosses and lichens dominate in the nest material, likely collected from the nearby vegetation formations. The Antarctic hairgrass in these conditions is mostly found in nests located directly within hairgrass formations. However, on the more southern Argentine Islands, kelp gulls routinely use D. antarctica and some mosses, transferring them from coastal hill tops where snow generally disappears earlier. Here, the gulls appear to be selective still, as they rarely use some mosses, such as Polytrichum strictum, that are abundant near the nesting locations. In the Argentine Islands area, we documented long-range transfer of the Antarctic hairgrass and some other vegetation materials from places of abundance to bare rocks of low islands lacking developed vegetation. This demonstrates the potential of the gulls to serve as dispersal and gene pool exchange agents for the local terrestrial biota in the maritime Antarctic, especially between highly isolated populations from small islands and ice-free areas.

Existing osteoporosis models in sheep exhibit some disadvantages, e.g., challenging surgical procedures, serious ethical concerns, failure of reliable induction of substantial bone loss, or lack of comparability to the human condition. This study aimed to compare bone morphological and mechanical properties of old and young sheep, and to evaluate the suitability of the old sheep as a model for senile osteopenia. The lumbar vertebral body L3 of female merino sheep with two age ranges, i.e., old animals (6–10 years; n = 41) and young animals (2–4 years; n = 40), was analyzed concerning its morphological and mechanical properties by bone densitometry, quantitative histomorphometry, and biomechanical testing of the corticalis and/or central spongious region. In comparison with young sheep, old animals showed only marginally diminished bone mineral density of the vertebral bodies, but significantly decreased structural (bone volume, − 15.1%; ventral cortical thickness, − 11.8%; lateral cortical thickness, − 12.2%) and bone formation parameters (osteoid volume, osteoid surface, osteoid thickness, osteoblast surface, all − 100.0%), as well as significantly increased bone erosion (eroded surface, osteoclast surface). This resulted in numerically decreased biomechanical properties (compressive strength; − 6.4%). Old sheep may represent a suitable model of senile osteopenia with markedly diminished bone structure and formation, and substantially augmented bone erosion. The underlying physiological aging concept reduces challenging surgical procedures and ethical concerns and, due to complex alteration of different facets of bone turnover, may be well representative of the human condition.

Objective: Electrical impedance tomography (EIT) is a non-invasive and relatively cheap imaging technique allowing continuous monitoring of lung function at the bedside. However, image reconstruction and processing are not yet standardized for clinical use, limiting comparability and reproducibility between studies. In addition, optimal reconstruction settings still have to be identified for different clinical applications. In this work (i) a systematic way to select ‘good’ EIT algorithm parameters is developed and (ii) an evaluation of these parameters in terms of correct functional imaging and consistency is performed. Approach: First, 19 200 reconstruction models are generated by full factorial design of experiment in 5D space. Then, in order to quantify the quality of reconstruction, known conductivity changes are introduced and figures of merit (FoM) are calculated from the response image. These measures are further used to select a subset of reconstruction models, matching certain FoM thresholds, and are then used for in vivo evaluation. For this purpose, EIT images of one piglet are reconstructed to assess changes in tidal impedance and end-expiratory lung impedance, at positive end expiratory pressure of 0 and 15 cmH2O. From ground truth spirometry measurements, physiological criteria are formulated and the subset of models is further reduced. Finally, the remaining reconstruction models are evaluated on physiological data gathered from published data in the literature to assess the generalization possibilities. Main results: Parametrization of EIT image reconstruction has a strong influence on the resulting FoM and the derived physiological parameter. While numerous reconstruction models showed reasonable values for a single parameter, in total only 12 matched all simulation and physiological criteria. After validation on further physiological data, only a single reconstruction model remained with a noise figure of 0.3, target size of 0.08, weight radius of 0.3, normalized voltage and strong weighting of lung and heart regions. Furthermore, the relationship between the reconstruction settings and some FoM could be partly explained by using a linear statistical model. Significance: The quest for standard reconstruction settings is highly relevant for future clinical applications. Simulation measures might help to assess the quality of the reconstruction models, but further evaluation of more data and different experimental settings is required.

Objective To evaluate the pharmacokinetics and selected pharmacodynamic effects of a commercially available l -methadone/fenpipramide combination administered to isoflurane anaesthetized ponies. Study design Prospective single-group interventional study. Animals A group of six healthy adult research ponies (four mares, two geldings). Methods Ponies were sedated with intravenous (IV) detomidine (0.02 mg kg–1) and butorphanol (0.01 mg kg–1) for an unrelated study. Additional IV detomidine (0.004 mg kg–1) was administered 85 minutes later, followed by induction of anaesthesia using IV diazepam (0.05 mg kg–1) and ketamine (2.2 mg kg–1). Anaesthesia was maintained with isoflurane in oxygen. Baseline readings were taken after 15 minutes of stable isoflurane anaesthesia. l -Methadone (0.25 mg kg–1) with fenpipramide (0.0125 mg kg–1) was then administered IV. Selected cardiorespiratory variables were recorded every 10 minutes and compared to baseline using the Wilcoxon signed-rank test. Adverse events were recorded. Arterial plasma samples for analysis of plasma concentrations and pharmacokinetics of l -methadone were collected throughout anaesthesia at predetermined time points. Data are shown as mean ± standard deviation or median and interquartile range (p Results Plasma concentrations of l -methadone showed a rapid initial distribution phase followed by a slower elimination phase which is best described with a two-compartment model. The terminal half-life was 44.3 ± 18.0 minutes, volume of distribution 0.43 ± 0.12 L kg–1 and plasma clearance 7.77 ± 1.98 mL minute–1 kg–1. Mean arterial blood pressure increased from 85 (±16) at baseline to 100 (±26) 10 minutes after l -methadone/fenpipramide administration (p = 0.031). Heart rate remained constant. In two ponies fasciculations occurred at different time points after l -methadone administration. Conclusions and clinical relevance Administration of a l -methadone/fenpipramide combination to isoflurane anaesthetized ponies led to a transient increase in blood pressure without concurrent increases in heart rate. Pharmacokinetics of l -methadone were similar to those reported for conscious horses administered racemic methadone.

An enantioselective assay for the determination of methadone and its main metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine in equine plasma based on capillary electrophoresis with highly sulfated γ-cyclodextrin as chiral selector and electrokinetic analyte injection is described. The assay is based on liquid/liquid extraction of the analytes at alkaline pH from 0.1 mL plasma followed by electrokinetic sample injection of the analytes from the extract across a buffer plug without chiral selector. Separation occurs cationically at normal polarity in a pH 3 phosphate buffer containing 0.16% (w/v) of highly sulfated γ-cyclodextrin. The developed assay is precise (intra- and interday RSD < 4% and < 7%, respectively), is capable to determine enantiomer levels of methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine in plasma down to 2.5 ng/mL, and was successfully applied to monitor enantiomer drug and metabolite levels in plasma of a pony that was anesthetized with racemic ketamine and isoflurane and received a bolus of racemic methadone and a bolus followed by constant rate infusion of racemic methadone. The data suggest that the assay is well suited for pharmacokinetic purposes.

OBJECTIVE In EIT applications to the thorax, a single electrode plane has typically been used to reconstruct a transverse 2D 'slice'. However, such images can be misleading as EIT is sensitive to contrasts above and below the electrode plane, and ventilation and aeration inhomogeneities can be distributed in complex ways. Using two (or more) electrode planes, 3D EIT images may be reconstructed, but 3D reconstructions are currently little used in thoracic EIT. In this paper, we investigate an incremental pathway towards 3D EIT reconstructions, using two electrode planes to calculate improved transverse slices as an intermediate step. We recommend a specific placement of electrode planes, and further demonstrate the feasibility of multi-slice reconstruction in two species. APPROACH Simulations of the forward and reconstructed sensitivities were analysed for two electrode planes using a 'square' pattern of electrode placement as a function of two variables: the stimulation and measurement 'skip', and the electrode plane separation. Next, single- versus two-plane measurements were compared in a horse and in human volunteers. We further show the feasibility of 3D reconstructions by reconstructing multiple transverse and, unusually, frontal slices during ventilation. MAIN RESULTS Using two electrode planes leads to a reduced position error and improvement in off-plane contrast rejection. 2D reconstructions from two-plane measurements showed better separation of lungs, as compared to the single plane measurements which tend to push contrasts in the center of the image. 3D reconstructions of the same data show anatomically plausible images, inside as well as outside the volume between the two electrode planes. SIGNIFICANCE Based on the results, we recommend EIT electrode planes separated by less than half of the minimum thoracic dimension with a 'skip 4' pattern and 'square' placement to produce images with good slice selectivity.

Alongside the obesity epidemic, the prevalence of maternal diabetes is rising worldwide, and adverse effects on fetal development and metabolic disturbances in the offspring's later life have been described. To clarify whether metabolic programming effects are due to mild maternal hyperglycemia without confounding obesity, we investigated wild-type offspring of INSC93S transgenic pigs, which are a novel genetically modified large-animal model expressing mutant insulin (INS) C93S in pancreatic β-cells. This mutation results in impaired glucose tolerance, mild fasting hyperglycemia and insulin resistance during late pregnancy. Compared with offspring from wild-type sows, piglets from hyperglycemic mothers showed impaired glucose tolerance and insulin resistance (homeostatic model assessment of insulin resistance: +3-fold in males; +4.4-fold in females) prior to colostrum uptake. Targeted metabolomics in the fasting and insulin-stimulated state revealed distinct alterations in the plasma metabolic profile of piglets from hyperglycemic mothers. They showed increased levels of acylcarnitines, gluconeogenic precursors such as alanine, phospholipids (in particular lyso-phosphatidylcholines) and α-aminoadipic acid, a potential biomarker for type 2 diabetes. These observations indicate that mild gestational hyperglycemia can cause impaired glucose tolerance, insulin resistance and associated metabolic alterations in neonatal offspring of a large-animal model born at a developmental maturation status comparable to human babies.

ObjectivesIntracranial arteriosclerotic disease is a relevant cause of ischemic stroke worldwide with a high recurrence rate despite best medical treatment. Following the SAMMPRIS trial, endovascular treatment has remained a second-line therapy. Meanwhile, there has been significant advances in device technology. SeQuent Please NEO is a novel polymer-free, drug-coated (paclitaxel/iopromide) balloon (DCB) primarily designed for cardiology. Because of its high flexibility and pushability, it may also be suitable for intracranial use. The aim of this study was to assess the feasibility and safety of SeQuent Please NEO DCB in symptomatic intracranial severe stenosis.MethodsA single-center retrospective cohort study of patients with symptomatic intracranial severe stenosis treated with SeQuent Please NEO DCB was performed at a tertiary stroke center.ResultsTen patients (all men, median age 73 years (IQR 69–77)) were included. Median pre-treatment stenosis grade was 78% (IQR 75–80%) with four internal carotid artery, two mid-basilar artery, and four vertebral artery lesions. Median post-treatment stenosis grade was 50% (IQR 45–53%). Successful angioplasty was achieved in all cases without technical failure. There were no cases of peri-procedural reocclusion and no deaths at median follow-up of 3 months (IQR 2–3).ConclusionIn this pilot study, SeQuent Please NEO DCB was feasible and safe in the treatment of symptomatic intracranial severe stenosis. It might represent a promising alternative to medical treatment in selected cases.

Objective To assess changes in the distribution in pulmonary ventilation in anaesthetized ponies using Electrical Impedance Tomography (EIT). Study design Prospective experimental study Animals Eight adult ponies geldings Methods General anaesthesia was induced and maintained using isoflurane in oxygen with volume-controlled ventilation [tidal volume (10 mL kg-1), respiratory rate (8 – 12 breaths minute-1)] to maintain end-tidal carbon dioxide between 35 and 40 mmHg (4.66–5.32 kPa). Regional distribution of ventilation was assessed with EIT (plane of 5th to 6th intercostal space) at 30, 60 and 90 minutes after intubation. The resulting functional images were divided into four regions of interest (ROI, A - D) to determine 1) the ratio of tidal volume distribution between dependent to non-dependent lung (D/ND), 2) changes in distribution within the lungs in latero-lateral direction. The centre of ventilation (COV) was calculated. The dimension of the chest in latero-lateral (W) and dorso-ventral (H) direction was measured at the height of the withers and the W/H ratio was calculated. The influence of time on D/ND ratio, COV and ROI A – D were analysed with ANOVA followed by post-hoc Bonferroni tests. Pearson correlation coefficient and the coefficient of determination (r2) were calculated to evaluate the relationship between W/H ratio and D/ND ratio, and COV. Statistical significance was set at p < 0.05. Results The median D/ND ratio (T30 to T90) was 0.67 (0.40 -1.01) and for COV 31.15% (11.20-45.20), confirming the expected uneven distribution of ventilation. The D/ND ratio had a moderate negative correlation with the W/H ratio (r = -0.68, r2 = 0.46, p = 0.000), while the COV did not correlate with the W/H ratio (r = -0.04). Conclusion and clinical relevance: Uneven ventilation in mechanically ventilated right laterally recumbent anaesthetised ponies occurs within thirty minutes and changed little over the following 60 minutes.