Search

Three-dimensional ring electrode arrays can provide means for highly-parallelized nanoparticle-impact electrochemistry within bulk solution.

Background Preclinical and clinical data following acute myocardial infarction (MI) and reperfusion have shown a bimodal pattern of edematous myocardium at risk (MaR) on cardiovascular magnetic resonance (CMR) imaging during the first week [1,2]. In contrary, there have also been data demonstrating that MaR is stable during the first week in patients using contrast-enhanced steady-state free precession (CE-SSFP) imaging [3]. Purpose To use a comprehensive CMR protocol to assess the dynamics of edematous MaR during the first week following acute experimental MI. Methods Acute myocardial ischemia was induced in seven pigs by endovascular balloon occlusion in the left anterior descending artery with reperfusion after 40 minutes. CMR was performed at baseline, at 120 minutes, 24 hours and seven days post-reperfusion on a 1.5T scanner. The CMR protocol comprised of a prototype T2-SSFP sequence where two experiments with 16 echo times (T2 mapping16) and with 10 echo times (T2 mapping10) [1] were performed. After contrast administration, a short-axis CE-SSFP stack and late gadolinium enhancement (LGE) images were acquired. T2-maps were acquired in a mid-apical ventricular short-axis slice corresponding to the same anatomical level at all time points. All image analysis was performed using designated software. Severity of MaR was measured by placing a region of interest in the ischemic area on T2 maps and extent of MaR was assessed by delineating hyperintense areas in CE-SSFP short-axis stacks. Data is presented as mean ± SD and one-way ANOVA was used followed by Tukey's multiple comparison test. Results An example of all acquired CMR sequences is shown in Figure 1, with red arrows depicting the extent of edematous MaR. Figure 2 shows the severity of MaR by T2 values from T2 mapping16 where T2 values were significantly lower at 24 hours compared to 120 minutes post-reperfusion (P Conclusion The severity and extent of edematous myocardium at risk does not follow a bimodal pattern over the course of one week. However, absolute T2 values differ between T2 mapping sequences and therefore a standardization of a CMR protocol for the assessment of MaR is of importance. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Swedish Heart-Lung Foundation and The Medical Faculty of Lund University (ALF)

This work demonstrates a lateral flow assay concept on the basis of stochastic-impact electrochemistry. To this end, we first elucidate requirements to employ silver nanoparticles as redox-active labels. Then, we present a prototype that utilizes nanoimpacts from biotinylated silver nanoparticles as readouts to detect free biotin in solution based on competitive binding. The detection is performed in a membrane-based microfluidic system, where free biotin and biotinylated particles compete for streptavidin immobilized on embedded latex beads. Excess nanoparticles are then registered downstream at an array of detection electrodes. In this way, we establish a proof of concept that serves as a blueprint for future "digital" lateral flow sensors.

The ABC transporter ABCA7 has been found to be aberrantly expressed in a variety of cancer types, including breast cancer. We searched for specific epigenetic and genetic alterations and alternative splicing variants of ABCA7 in breast cancer and investigated whether these alterations are associated with ABCA7 expression. By analyzing tumor tissues from breast cancer patients, we found CpGs at the exon 5–intron 5 boundary aberrantly methylated in a molecular subtype-specific manner. The detection of altered DNA methylation in tumor-adjacent tissues suggests epigenetic field cancerization. In breast cancer cell lines, DNA methylation levels of CpGs in promoter-exon 1, intron 1, and at the exon 5–intron 5 boundary were not correlated with ABCA7 mRNA levels. By qPCR involving intron-specific and intron-flanking primers, we identified intron-containing ABCA7 mRNA transcripts. The occurrence of intron-containing transcripts was neither molecular subtype-specific nor directly correlated with DNA methylation at the respective exon–intron boundaries. Treatment of breast cancer cell lines MCF-7, BT-474, SK-BR3, and MDA-MB-231 with doxorubicin or paclitaxel for 72 h resulted in altered ABCA7 intron levels. Shotgun proteomics revealed that an increase in intron-containing transcripts was associated with significant dysregulation of splicing factors linked to alternative splicing.

Durch den Einsatz von Raumlufttechnischen (RLT) Anlagen lassen sich Schadstoffkonzentrationen in Räumen effektiv reduzieren. Dies gilt grundsätzlich auch für die Konzentration von luftgetragenen Krankheitserregern. Es existieren Anlagentypen, die aufgrund ihrer Konfiguration ein Risikopotential bieten. Hierbei kann kontaminierte Abluft über die RLT-Anlage in nicht kontaminierte Bereiche verteilt werden. In dieser Studie wurde betrachtet, wie hoch die Übertragung derartiger Kontaminationen durch den Umluftbetrieb sowie durch eventuell vorhandene interne Leckagen in zentralen und dezentralen Lüftungsanlagen ist. Hierfür wurden verschiedene Fälle ausgewählt und die Verdünnung der Konzentration bestimmt. Neben einer dezentralen Lüftung für einen einzelnen Raum wurden zentrale Lüftungssysteme mit einer unterschiedlichen Anzahl angeschlossener Räume und damit verschiedenen Gesamtvolumenströmen betrachtet. Bei dem dezentralen Fall und einem Umluftanteil von 40 % am Zuluftvolumenstrom liegt die Verdünnung bei 60 %. Da ein dezentrales System typischerweise raumweise arbeitet, ist eine Übertragung in andere Räume über die raumlufttechnische Anlage ausgeschlossen. Bei einem zentralen System erhöht sie sich mit steigender Anzahl der versorgten Räume auf 80 – ca. 95 % unter der Annahme einer einzigen Kontaminationsquelle in nur einem der Räume. Die Versorgung mehrerer Räume führt gleichzeitig zu einem höheren Gesamtzuluftvolumenstrom im Vergleich zu dem dezentralen Fall. Die Verdünnung vergrößert sich je geringer der Leckage- bzw. Umluftanteil am Zuluftvolumenstrom ist. Im nächsten Schritt wurde für ein kleines Büro ein Vergleich der Belastung pro m3 Raumvolumen als Maß für die Kontamination mit vier verschiedenen Lüftungsszenarien (unbelüftet sowie nach DIN EN 16798-1 Kategorie I bis III) vorgenommen. Abschließend wurden für drei Bürogrößen Belastungen für die Fälle mit Umluftanteilen von 20 % und von 40 % berechnet und mit Luftvolumenströmen nach Kategorie II und III verglichen. Außerdem wurde für eine Anlage ohne Umluft betrachtet, wie sich interne Leckagen (bspw. durch Wärmerückgewinnungssysteme selbst oder den Einbau dieser) von 5% auswirken. Es ist zu erkennen, dass sich die Luftqualität bei der Nutzung einer dezentralen Lüftungsanlage und einem Umluftanteil von 40 % um eine Kategorie verschlechtert. Zu beachten ist, dass es sich um eine vereinfachte Rechnung des ungünstigsten Falls handelt, bei der die Wirkung von Filtern nicht betrachtet wurde. Bei Einbeziehung von Filterleistungen in die Berechnung ist mit einer Verringerung der Belastung zu rechnen [1]. Insgesamt ist zu bemerken, dass durch den Einsatz von Umluft in zentralen Lüftungssystemen das Risiko der Übertragungen von Kontaminationen aus der Abluft in die Zuluft nur sehr gering erhöht wird. Das Vorhandensein von Leckagen (Annahme 5%) durch Wärmerückgewinnungssysteme führt zu einem unerheblichen Einfluss. Dennoch sollte stets der Außenluftluftanteil möglichst hoch sein, um die Raumlufthygiene auf einem hohen Standard zu halten.

Peripheral nerve interfacing (PNI) has a high clinical potential for treating various diseases, like obesity or diabetes. However, currently existing electrodes present challenges to the interfacing procedure, which limits their clinical application, in particular, when targeting small peripheral nerves (200 μm). To improve the electrode handling and implantation, we fabricate a nerve interface that can fold itself to a cuff around a small nerve, triggered by the body moisture during insertion. We achieve this folding by printing a bilayer of a flexible polyurethane printing resin and a highly swelling sodium acrylate hydrogel using photopolymerization. When immersed in an aqueous liquid, the hydrogel swells and folds the electrode softly around the nerve. Furthermore, the electrodes are robust, can be stretched (20%), and bend to facilitate the implantation due to the use of soft and stretchable printing resins as substrates and a microcracked gold film as conductive layer. We demonstrate the straightforward implantation and extraction of the electrode as well as stimulation and recording capabilities on a small peripheral nerve in vivo. We believe that such simple and robust to use self-folding electrodes will pave the way for bringing PNI to a broader clinical application. This article is protected by copyright. All rights reserved.

Acute myocardial infarction (AMI) can progress to heart failure, which has a poor prognosis. Normally, 60% of stroke volume (SV) is attributed to the longitudinal ventricular shortening and lengthening evident in the atrioventricular plane displacement (AVPD) during the cardiac cycle, but there is no information on how the relationship changes between SV and AVPD before and after AMI. Therefore, the aim of this study was to determine how SV depends on AVPD before and after AMI in two swine models. Serial cardiac magnetic resonance imaging was carried out before and 1–2 h after AMI in a microembolization model ( n = 12) and an ischemia-reperfusion model ( n = 14). A subset of pigs ( n = 7) were additionally imaged at 24 h and at 7 days. Cine and late gadolinium enhancement images were analyzed for cardiac function, AVPD measurements and infarct size estimation, respectively. AVPD decreased ( P < 0.05) in all myocardial regions after AMI, with a concomitant SV decrease ( P < 0.001). The ischemia-reperfusion model affected SV to a higher degree and had a larger AVPD decrease than the microembolization model (−29 ± 14% vs. −15 ± 18%; P < 0.05). Wall thickening decreased in infarcted areas ( P < 0.001), and A-wave AVPD remained unchanged ( P = 0.93) whereas E-wave AVPD decreased ( P < 0.001) after AMI. We conclude that AVPD is coupled to SV independent of infarct type but likely to a greater degree in ischemia-reperfusion infarcts compared with microembolization infarcts. AMI reduces diastolic early filling AVPD but not AVPD from atrial contraction. These findings shed light on the physiological significance of atrioventricular plane motion when assessing acute and subacute myocardial infarction. NEW & NOTEWORTHY The link between cardiac longitudinal motion, measured as atrioventricular plane displacement (AVPD), and stroke volume (SV) is investigated in swine after acute myocardial infarction (AMI). This cardiac magnetic resonance study demonstrates a close coupling between AVPD and SV before and after AMI in an experimental setting and demonstrates that this connection is present in ischemia-reperfusion and microembolization infarcts, acutely and during the first week. Furthermore, AVPD is equally and persistently depressed in infarcted and remote myocardium after AMI.

Extended half-life (EHL) factor therapies are needed to reduce the burden of prophylaxis and improve treatment adherence in patients with hemophilia. BAX 826 is a novel polysialylated full-length recombinant factor VIII [polysialyic acid (PSA) rFVIII] with improved pharmacokinetics (PK), prolonged pharmacology, and maintained safety attributes to enable longer-acting rFVIII therapy. In factor VIII (FVIII)-deficient hemophilic mice, PSArFVIII showed a substantially higher mean residence time (>2-fold) and exposure (>3-fold), and prolonged efficacy in tail-bleeding experiments (48 vs. 30 hours) compared with unmodified recombinant FVIII (rFVIII), as well as a potentially favorable immunogenicity profile. Reduced binding to a scavenger receptor (low-density lipoprotein receptor-related protein 1) and von Willebrand factor (VWF) as well as a largely VWF-independent circulation time in mice provide a rationale for prolonged BAX 826 activity. The significantly improved PK profile versus rFVIII was confirmed in cynomolgus monkeys [mean residence time: 23.4 vs. 10.1 hours; exposure (area under the curve from time 0 to infinity): 206 vs. 48.2 IU/ml⋅h] and is in line with results from rodent studies. Finally, safety and toxicity evaluations did not indicate increased thrombogenic potential, and repeated administration of BAX 826 to monkeys and rats was well tolerated. The favorable profile and mechanism of this novel experimental therapeutic demonstrated all of the requirements for an EHL-rFVIII candidate, and thus BAX 826 was entered into clinical assessment for the treatment of hemophilia A. SIGNIFICANCE STATEMENT: Prolongation of FVIII half-life aims to reduce the burden of prophylaxis and improve treatment outcomes in patients with hemophilia. This study shows that polysialylation of PSArFVIII resulted in prolongations of rFVIII circulation time and procoagulant activity, together with a favorable nonclinical safety profile of the experimental therapeutic.

Insufficiency of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin motif repeats-13) is the cause of thrombotic thrombocytopenic purpura (TTP) and contributes in microangiopathy in sickle cell disease (SCD). Recombinant ADAMTS13 effectively cleaves prothrombotic ultra-large von Willebrand factor (VWF) multimers. It is being tested as replacement therapy for TTP, and at supra-physiologic concentrations, for moderating vaso-occlusive crisis in SCD. Deficiencies of VWF, or concomitant treatment with antithrombotic drugs, could pose risks for increased bleeds in these patient populations. The purpose of the experiments was to evaluate the potential of exaggerated pharmacology and temporary bleeding risks associated with rADAMTS13 administration. We utilized safety studies in monkey and tested the effects of administering maximum-feasible doses of rADAMTS13 on nonclinical safety and spontaneous or aggressive bleeds in the rat model. Evaluation of pharmacokinetics, toxicity profiles, and challenge in a tail-tip bleeding model show that treatment with rADAMTS13 did not increase bleeding tendency, either alone, or in combination with enoxaparin or acetylsalicylic-acid. These novel findings demonstrate absence of rADAMTS13 exaggerated pharmacology without spontaneous or aggravated bleeds even at supra-physiologic (>100-fold) plasma concentrations.

The H+,K+-ATPase was identified as the primary proton secretory pathway in the gastric parietal cell and is the pharmacological target of agents suppressing acid secretion. Recently, we identified a second acid secretory protein expressed in the parietal cell, the vacuolar H+-ATPase (V-type ATPase). The aim of the present study was to further characterize H+-ATPase activation by modulations in extracellular calcium via the calcium sensing receptor (CaSR). Isolated gastric glands were loaded with the pH indicator dye BCECF-AM [2′,7′-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethyl ester] to measure intracellular pH. Experiments were conducted in the absence of sodium and potassium to monitor H+-ATPase-specific transport activity. CaSR was activated with the calcimimetic R568 (400 nM) and/or by modulations in extracellular Ca2+. Elevation in calcium concentrations increased proton extrusion from the gastric parietal cell. Allosteric modification of the CaSR via R568 and calcium increased vacuolar H+-ATPase activity significantly (ΔpH/minlowCa2+(0.1mM) = 0.001 ± 0.001, ΔpH/minnormalCa2+(1.0mM) = 0.033 ± 0.004, ΔpH/minhighCa2+(5.0mM) = 0.051 ± 0.005). Carbachol significantly suppressed calcium-induced gastric acid secretion via the H+-ATPase under sodium- and potassium-free conditions. We conclude that the V-type H+-ATPase is tightly linked to CaSR activation. We observed that proton pump inhibitor (PPI) exposure does not modulate H+-ATPase activity. This elevated blood calcium activation of the H+-ATPase could provide an explanation for recurrent reflux symptoms while taking a PPI therapy.NEW & NOTEWORTHY This study emphasizes the role of the H+-ATPase in acid secretion. We further demonstrate the modification of this proton excretion pathway by extracellular calcium and the activation of the calcium sensing receptor CaSR. The novelty of this paper is based on the modulation of the H+-ATPase via both extracellular Ca (activation) and the classical secretagogues histamine and carbachol (inactivation). Both activation and inactivation of this proton pump are independent of PPI modulation.

Background Magnetic resonance imaging (MRI) biomarkers can diagnose and prognosticate kidney disease. Renal volume validation studies are however scarce, and measurements are limited by use of contrast agent or advanced post-processing. Purpose To validate a widely available non-contrast-enhanced MRI method for quantification of renal cortical and medullary volumes in pigs; investigate observer variability of cortical and medullary volumes in humans; and present reference values for renal cortical and medullary volumes in adolescents. Materials and Methods Cortical and medullary volumes were quantified from transaxial in-vivo water-excited MR images in six pigs and 15 healthy adolescents (13–16years). Pig kidneys were excised, and renal cortex and medulla were separately quantified by the water displacement method. Both limits of agreement by the Bland-Altman method and reference ranges are presented as 2.5–97.5 percentiles. Results Agreement between MRI and ex-vivo quantification were -7 mL (-10–0 mL) for total parenchyma, -4 mL (-9–3 mL) for cortex, and -2 mL (-7–2 mL) for medulla. Intraobserver variability for pig and human kidneys were 2 (boys) and 56–103 mL/m2 (girls) for total parenchyma, 39–62 mL/m2 and 36–68 mL/m2 for cortex, and 16–45 mL/m2 and 17–42 mL/m2 for medulla. Conclusion The proposed widely available non-contrast-enhanced MRI method can quantify cortical and medullary renal volumes and can be directly implemented clinically.

For various engineering applications, the analysis and prediction of damage onset and propagation within ductile materials under thermo-mechanical loading conditions play a crucial role. However, finite element modeling of the influence of the temperature on plastic flow and damage evolution and the back-coupling of theses dissipative processes on the temperature field remains a challenging task, until today. To this end, a thermo-mechanically coupled two-surface damage-plasticity theory is derived in a thermodynamically consistent manner for large deformations. It can be considered as the thermo-mechanically coupled extension of a corresponding isothermal model, which was proposed recently by Brepols et al. (2020). In this novel theory, the heat generation associated with thermo-elastic coupling and irreversible processes (i.e. damage and plasticity) is derived from the first law of thermodynamics. To overcome the mesh-dependence of conventional local damage models, a gradient-extension based on the micromorphic approach of Forest (2009, 2016) is employed. Besides the theoretical development, the algorithmic implementation into finite elements is discussed, including the computation of the required tangent operators via automatic differentiation. Finally, the fully coupled multi-physical formulation is verified regarding mesh-insensitive predictions of e.g. strain localization, local heat accumulation, material and thermal-softening, as well as crack propagation and back-coupling effects on the temperature field. Quantitative and qualitative comparisons of the model’s predictions to experimental data reveal the promising potential of the numerically robust and flexible theory.

BACKGROUND The oxidative deterioration of vegetable oils is commonly measured by the peroxide value, thereby not considering the contribution of individual lipid hydroperoxide isomers, which might have different bioactive effects. Thus, the formation of 9- and 13-hydroperoxy octadecadienoic acid (9-HpODE and 13- HpODE), was quantitated after short-term heating and conditions representative of long-term domestic storage in samples of linoleic acid, canola, sunflower and soybean oil, by means of stable isotope dilution analysis-LC-MS/MS. RESULTS While heating of pure linoleic acid at 180 °C for 30 min led to an almost complete loss of 9-HpODE and 13-HpODE, heating of canola, sunflower and soybean oil resulted in the formation of 5.74 ± 3.32, 2.00 ± 1.09, 16.0 ± 2.44 mM 13-HpODE and 13.8 ± 8.21, 10.0 ± 6.74 and 45.2 ± 6.23 mM 9-HpODE. An almost equimolar distribution of the 9- and 13-HpODE was obtained during household-representative storage conditions after 56 days, whereas under heating conditions, an approximately 2.4-, 2.8- and 5.0-fold (p ≤ 0.001) higher concentration of 9-HpODE than 13-HpODE was detected in canola, soybean and sunflower oil, respectively. CONCLUSION A temperature-dependent distribution of HpODE regioisomers could be shown in vegetable oils suggesting them as markers of lipid oxidation in oils used for short-term heating.

The aim of this article was to investigate the temperature increase of the external root surface during laser-assisted endodontic treatment using a diode laser (980 nm) in a microchopped mode.Ten freshly extracted, human maxillary incisors with mature apices were collected, prepared to size F4 at working length (ProTaper; Dentsply Maillefer, Ballaigues, Switzerland), mounted to a holder, and irradiated (using spiral movements in coronal direction) with a diode laser (GENTLEray 980 Classic Plus; KaVo, Biberach, Germany) with a 200 μm fiber in four different treatment groups: Group 1 (control group) was irradiated in six cycles of 5-sec irradiation/20-sec pause with 2.5 W in the pulse mode. Groups 2 to 4 were irradiated at six cycles of 5-sec irradiation/20-sec pause in the microchopped mode (Group 2-1.6 W; Group 3-2.0 W; Group 4-2.5 W). The applied mode was 25 ms on/25 ms off. Within the on period, the laser delivered an intermittent sequence of energy complexes and the maximum output was equal to the nominated output of the device (12 W). Canals were kept moist by sterile saline irrigation in between irradiations, and temperature changes were continuously measured using a thermal imaging camera. Recordings were analyzed by a mixed model (analysis of variance [ANOVA] for repeated measurements).The highest mean of temperature rise, 1.94°C ± 1.07°C, was measured in Group 4, followed by Group 3 (1.74°C ± 1.22°C) and Group 2 (1.58°C ± 1.18°C). The lowest increase occurred in Group 1 (1.06°C ± 1.20°C). There was a significant difference (p = 0.041) between the groups. Significant differences were found between Groups 1 and 4 (p = 0.007) and 1 and 2 (p = 0.035). In addition, a marginally significant difference between Groups 1 and 2 (p = 0.052) was noted. There was no significant difference between Groups 2, 3, and 4. Despite the low mean values reported, the highest temperature increase (+5.7°C) was measured in one of the specimens of treatment Group 2 at the middle third.Under the conditions used and within the limitations of the study, the microchopped diode laser irradiation is a safe possible treatment option in laser-assisted endodontic treatment, concerning the temperature elevation on the external root surface.

Pseudomyxoma peritonei is a rare tumorous disease with various grades of malignancy and is characterized by production of mucinous and gelatinous masses. Development of pseudomyxoma peritonei is usually associated with rupture of appendiceal mucinous tumors and other mucinous tumors of the gastrointestinal tract or ovaries. Pseudomyxoma peritonei is usually divided into three types: low-grade, high-grade, and high-grade with signet ring cells. Staging of the disease is determined by the peritoneal cancer index. Clinical findings are highly variable depending on disease staging. The typical finding of#8220;jelly belly#8221; syndrome worsens with disease progression. The diagnosis is based on the pre-operative cure by imaging methods, especially computed tomography.The Sugarbaker method involves maximal removal of tumorous masses, so-called cytoreductive surgery, and perioperative intraabdominal application of hot cytostatics (hyperthermic intraperitoneal chemotherapy) with the aim of achieving maximal liquidation of tumorous processes.Our results are comparable with previous published data and confirm high effectivness of this method. The results show statistically very significant extention of overall survival, disease free interval with acceptable lethality 0-12 % and morbidity 27-56%. These results promote this method as the gold standard of treatment of pseudomyxoma peritonei in selected patients.

Spectroscopy in the femtosecond time domain can both reveal fundamental insight in the properties of materials and provide relevant experimental tests for functional systems. [...]

In a large group of patients, it is impossible to measure blood pressure using an upper arm cuff. An alternative, non-invasive method of blood pressure measurement is required for patients with severe limb deformities or obesity, for amputees, and in the emergency medicine. The device proposed here measures blood pressure in the cheek using a small pressure pad and a pump to occlude the cheek artery – arteria facialis – and assesses blood flow with an infrared light source and a detector. The infrared light signal is analysed to assess the systolic and diastolic blood pressure of the patient. Manual evaluation of the light intensity signal showed a good agreement between cheek blood pressure measurement and a reference measurement using an upper arm cuff.

Background: Pressure-volume (PV) loops provide a wealth of information on cardiac function but are not readily available in clinical routine or in clinical trials. This study aimed to develop and validate a noninvasive method to compute individualized left ventricular PV loops. Methods: The proposed method is based on time-varying elastance, with experimentally optimized model parameters from a training set (n=5 pigs), yielding individualized PV loops. Model inputs are left ventricular volume curves from cardiovascular magnetic resonance imaging and brachial pressure. The method was experimentally validated in a separate set (n=9 pig experiments) using invasive pressure measurements and cardiovascular magnetic resonance images and subsequently applied to human healthy controls (n=13) and patients with heart failure (n=28). Results: There was a moderate-to-excellent agreement between in vivo-measured and model-calculated stroke work (intraclass correlation coefficient, 0.93; bias, −0.02±0.03 J), mechanical potential energy (intraclass correlation coefficient, 0.57; bias, −0.04±0.03 J), and ventricular efficiency (intraclass correlation coefficient, 0.84; bias, 3.5±2.1%). The model yielded lower ventricular efficiency ( P P P P Conclusions: We have developed the first experimentally validated, noninvasive method to compute left ventricular PV loops and associated quantitative measures. The proposed method shows significant agreement with in vivo-derived measurements and could support clinical decision-making and provide surrogate end points in clinical heart failure trials.

Background Cardiovascular magnetic resonance (CMR) can be used to calculate myocardial extracellular volume fraction (ECV) by relating the longitudinal relaxation rate in blood and myocardium before and after contrast-injection to hematocrit (Hct) in blood. Hematocrit is known to vary with body posture, which could affect the calculations of ECV. The aim of this study was to test the hypothesis that there is a significant increase in calculated ECV values if the Hct is sampled after the CMR examination in supine position compared to when the patient arrives at the MR department. Methods Forty-three consecutive patients including various pathologies as well as normal findings were included in the study. Venous blood samples were drawn upon arrival to the MR department and directly after the examination with the patient remaining in supine position. A Modified Look-Locker Inversion recovery (MOLLI) protocol was used to acquire mid-ventricular short-axis images before and after contrast injection from which motion-corrected T1 maps were derived and ECV was calculated. Results Hematocrit decreased from 44.0 ± 3.7% before to 40.6 ± 4.0% after the CMR examination (p

The H

The design and characterization of a HHG source conceived for Time and Angle Resolved PhotoElectron Spectroscopy (TR-ARPES) experiments are presented. The harmonics are selected through a grating monochromator with an innovative design able to provide XUV radiation for two distinct TR-ARPES setups. © OSA 2018.

BACKGROUND The oxidative deterioration of vegetable oils is commonly measured by the peroxide value, thereby not considering the contribution of individual lipid hydroperoxide isomers, which might have different bioactive effects. Thus, the formation of 9‐ and 13‐hydroperoxy octadecadienoic acid (9‐HpODE and 13‐ HpODE), was quantified after short‐term heating and conditions representative of long‐term domestic storage in samples of linoleic acid, canola, sunflower and soybean oil, by means of stable isotope dilution analysis–liquid chromatography‐mass spectroscopy. RESULTS Although heating of pure linoleic acid at 180 °C for 30 min led to an almost complete loss of 9‐HpODE and 13‐HpODE, heating of canola, sunflower and soybean oil resulted in the formation of 5.74 ± 3.32, 2.00 ± 1.09, 16.0 ± 2.44 mmol L–1 13‐HpODE and 13.8 ± 8.21, 10.0 ± 6.74 and 45.2 ± 6.23 mmol L–1 9‐HpODE. An almost equimolar distribution of the 9‐ and 13‐HpODE was obtained during household‐representative storage conditions after 56 days, whereas, under heating conditions, an approximately 2.4‐, 2.8‐ and 5.0‐fold (P ≤ 0.001) higher concentration of 9‐HpODE than 13‐HpODE was detected in canola, soybean and sunflower oil, respectively. CONCLUSION A temperature‐dependent distribution of HpODE regioisomers could be shown in vegetable oils, suggesting their application as markers of lipid oxidation in oils used for short‐term heating. © 2017 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Here, we report on a novel narrowband High Harmonic Generation (HHG) light source designed for ultrafast photoelectron spectroscopy (PES) on solids. Notably, at 16.9 eV photon energy, the harmonics bandwidth equals 19 meV. This result has been obtained by seeding the HHG process with 230 fs pulses at 515 nm. The ultimate energy resolution achieved on a polycrystalline Au sample at 40 K is ∼22 meV at 16.9 eV. These parameters set a new benchmark for narrowband HHG sources and have been obtained by varying the repetition rate up to 200 kHz and, consequently, mitigating the space charge, operating with ≈ 3 × 10 7 electrons/s and ≈ 5 × 10 8 photons/s. By comparing the harmonics bandwidth and the ultimate energy resolution with a pulse duration of ∼105 fs (as retrieved from time-resolved experiments on bismuth selenide), we demonstrate a new route for ultrafast space-charge-free PES experiments on solids close to transform-limit conditions.Here, we report on a novel narrowband High Harmonic Generation (HHG) light source designed for ultrafast photoelectron spectroscopy (PES) on solids. Notably, at 16.9 eV photon energy, the harmonics bandwidth equals 19 meV. This result has been obtained by seeding the HHG process with 230 fs pulses at 515 nm. The ultimate energy resolution achieved on a polycrystalline Au sample at 40 K is ∼22 meV at 16.9 eV. These parameters set a new benchmark for narrowband HHG sources and have been obtained by varying the repetition rate up to 200 kHz and, consequently, mitigating the space charge, operating with ≈ 3 × 10 7 electrons/s and ≈ 5 × 10 8 photons/s. By comparing the harmonics bandwidth and the ultimate energy resolution with a pulse duration of ∼105 fs (as retrieved from time-resolved experiments on bismuth selenide), we demonstrate a new route for ultrafast space-charge-free PES experiments on solids close to transform-limit conditions.

The Western diet is characterized by a high consumption of heat-treated fats and oils. During deep-frying processes, vegetable oils are subjected to high temperatures which result in the formation of lipid peroxidation products. Dietary intake of oxidized vegetable oils has been associated with various biological effects, whereas knowledge about the effects of structurally-characterized lipid peroxidation products and their possible absorption into the body is scarce. This study investigates the impact of linoleic acid, one of the most abundant polyunsaturated fatty acids in vegetable oils, and its primary and secondary peroxidation products, 13-HpODE and hexanal, on genomic and metabolomic pathways in human gastric cells (HGT-1) in culture. The genomic and metabolomic approach was preceded by an up-to-six-hour exposure study applying 100 &micro, M of each test compound to the apical compartment in order to quantitate the compounds&rsquo, recovery at the basolateral side. Exposure of HGT-1 cells to either 100 &micro, M linoleic acid or 100 &micro, M 13-HpODE resulted in the formation of approximately 1 &micro, M of the corresponding hydroxy fatty acid, 13-HODE, in the basolateral compartment, whereas a mean concentration of 0.20 &plusmn, 0.13 &micro, M hexanal was quantitated after an equivalent application of 100 &micro, M hexanal. An integrated genomic and metabolomic pathway analysis revealed an impact of the linoleic acid peroxidation products, 13-HpODE and hexanal, primarily on pathways related to amino acid biosynthesis (p &lt, 0.05), indicating that peroxidation of linoleic acid plays an important role in the regulation of intracellular amino acid biosynthesis.

TPS6650 Background: Accurate evaluation of symptom intensities is essential for optimal cancer care and improving the quality of life of patients. An inappropriate interpretation of symptoms may lead to treatment outcomes failure, overdose of medication, or may leave the patients undertreated. However, the perception of symptoms can vary between the treating physician and patient. Physicians appear to underestimate the patient symptoms. And this variation in the perception of side effects can lead to wrong assumptions and subsequent treatment changes, affecting treatment effectiveness and quality of life. There is growing interest to enhance symptom monitoring during routine cancer care using patient-reported outcomes, leaving open the question of whether the benefits of systems to reveal self-reports outweigh their added cost. There are several tools for assessment of symptoms in oncology. In cancer treatment clinical trials, the standard source of adverse symptom data is clinician reporting by use of items from PRO-CTCAE, developed by NCI. To address these questions, we conducted a single-center prospective trial to test whether systematic tablet computer-based collection of patient-reported symptoms during chemotherapy treatment, with automated alerts to clinicians for severe adverse events (grade 3-4) will change in questionnaire score at 6 months compared with baseline. Secondary endpoints will include difference in unscheduled clinic visits frequency, and survival. Methods: Patients initiating chemotherapy at General Hospital Pula Oncology Clinic for advanced or metastatic gastrointestinal, lung, breast, genitourinary, or gynecologic cancers will be enrolled in a nonblinded, prospective trial of self-reporting of symptoms, compare with usual care. Patients receiving chemotherapy and their clinicians will be independently asked on the same day to complete 10 symptoms (including fatigue, pain, nausea, vomiting, diarrhea, dysgeusia, appetite, sleep disturbance, fever and hair loss). Participants will remain on study until discontinuation of cancer treatment, withdrawal, or death. All participants will provide written informed consent and followed for up to 28 months or until death. To compare how patient’s vs clinician’s reports relate to clinical events, a time-dependent Cox regression model adjusted for covariates including cancer type, age, sex, and education level will be used to measure associations between reaching particular grade severity thresholds with the risk of death and unscheduled clinic visits. Clinical trial information: 2019-000855-15.

Im Mittelpunkt des Fachbeitrages steht die Frage, uber welche bewegungsbezogenen (Zusatz-)Qualifikationen fruhpadagogische Fachkrafte verfugen, um den grundlegenden Bildungs­bereich »Bewegung« in der Kita-Praxis umzusetzen. Beantwortet wird diese Frage anhand erster Befunde einer im Rahmen des Verbundprojektes »Bewegung in der fruhen Kindheit« (BiK) durchgefuhrten Untersuchung mit fruhpadagogischen Fachkraften. Diese werden im Kontext der bewegungsbezogenen Fort- und Weiterbildungslandschaft betrachtet. Anhand der Ergebnisse werden erste Konsequenzen fur die Aus-, Fort- und Weiterbildungspraxis entwickelt.

Guard cells integrate various hormone signals and environmental cues to balance plant gas exchange and transpiration. The wounding-associated hormone jasmonic acid (JA) and the drought hormone abscisic acid (ABA) both trigger stomatal closure. In contrast to ABA however, the molecular mechanisms of JA-induced stomatal closure have remained largely elusive. Here, we identify a fast signaling pathway for JA targeting the K

Mucosal hypoxia is a common endpoint for many pathological processes including ischemic colitis, colonic obstruction and anastomotic failure. Previous studies suggest that hypoxia modulates colonic mucosal function through inhibition of chloride secretion. However, the molecular mechanisms underlying this observation are poorly understood. AMP-activated protein kinase (AMPK) is a metabolic energy regulator found in a wide variety of cells and has been linked to cystic fibrosis transmembrane conductance regulator (CFTR) mediated chloride secretion in several different tissues. We hypothesized that AMPK mediates many of the acute effects of hypoxia on human and rat colonic electrolyte transport.The fluorescent chloride indicator dye N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide was used to measure changes in intracellular chloride concentrations in isolated single rat colonic crypts. Ussing chamber experiments in human colonic mucosa were conducted to evaluate net epithelial ion transport.This study demonstrates that acute hypoxia inhibits electrogenic chloride secretion via AMPK mediated inhibition of CFTR. Pre-treatment of tissues with the AMPK inhibitor 6-[4-(2-piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo [1,5-a] pyrimidine (compound C) in part reversed the effects of acute hypoxia on chloride secretion.We therefore suggest that AMPK is a key component of the adaptive cellular response to mucosal hypoxia in the colon. Furthermore, AMPK may represent a potential therapeutic target in diseased states or in prevention of ischemic intestinal injury.

Studies investigating the activating and inhibitory actions of bioflavonoids on colonic function have yielded conflicting results. At low concentrations, flavonoids may stimulate chloride secretion while at higher concentrations they may have antisecretory actions in the colon. Naringenin (4',5,7-trihydroxyflavanone), found predominantly in citrus fruits, confers a protective effect against colorectal cancer and is purported to modulate secretory function in colonic cell lines. The aim of this study was to investigate the effects of naringenin on ion transport in rat and human colonic mucosae. Naringenin inhibited basal and stimulated chloride secretion in rat and human colonic mucosae mounted in Ussing chambers (IC(50) 330 μMol/L and 360 μMol/L respectively) and did not alter intracellular cAMP generation. Naringenin inhibited chloride secretion in MQAE (N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide) loaded crypts stimulated with forskolin. In BCECF (2',7'-bis-(2-carboxyethyl)-5-(and 6)-carboxyfluorescein acetoxymethyl ester) loaded crypts, naringenin caused an intracellular acidification (ΔpH/min=0.05 ± 0.004) which was sensitive to the Na-K-Cl co-transporter (NKCC) inhibitor bumetanide. In addition, the antisecretory effect of naringenin was not inhibited by blockade of barium sensitive basolateral K(+) transporters or by inhibition of Na+/H(+) exchange by amiloride. We propose that the antisecretory action of naringenin is due to inhibition of basolateral NKCC1 in rat and human colon.

Currently, there is a flurry of research interest on materials with an unconventional electronic structure, and we have already seen significant progress in their understanding and engineering towards real-life applications. The interest erupted with the discovery of graphene and topological insulators in the previous decade. The electrons in graphene simulate massless Dirac Fermions with a linearly dispersing Dirac cone in their band structure, while in topological insulators, the electronic bands wind non-trivially in momentum space giving rise to gapless surface states and bulk bandgap. Weyl semimetals in condensed matter systems are the latest addition to this growing family of topological materials. Weyl Fermions are known in the context of high energy physics since almost the beginning of quantum mechanics. They apparently violate charge conservation rules, displaying the ‘chiral anomaly’, with such remarkable properties recently theoretically predicted and experimentally verified to exist as low energy quasiparticle states in certain condensed matter systems. Not only are these new materials extremely important for our fundamental understanding of quantum phenomena, but also they exhibit completely different transport phenomena. For example, massless Fermions are susceptible to scattering from non-magnetic impurities. Dirac semimetals exhibit non-saturating extremely large magnetoresistance as a consequence of their robust electronic bands being protected by time reversal symmetry. These open up whole new possibilities for materials engineering and applications including quantum computing. In this review, we recapitulate some of the outstanding properties of WTe2, namely, its non-saturating titanic magnetoresistance due to perfect electron and hole carrier balance up to a very high magnetic field observed for the very first time. It also indicative of hosting Lorentz violating type-II Weyl Fermions in its bandstructure, again first predicted candidate material to host such a remarkable phase. We primarily focus on the findings of our ARPES, spin-ARPES, and time-resolved ARPES studies complemented by first-principles calculations.

Case report: Hepatoblastoma was diagnosed in a 4-year-old girl receiving growth hormone substitution therapy for short stature. Owing to multiple congenital malformations, VACTERL-H (vertebral, anal, cardiac, tracheal, renal and limb anomalies with hydrocephalus) association had been suggested. Elevated chromosomal breakage rates and G2 phase arrest induced by DNA-crosslinking agents in cellular assays confirmed the diagnosis of Fanconi anaemia (FA), a tumour susceptibility syndrome known to be associated with hepatocellular carcinoma following androgen therapy. Subsequent genotyping revealed biallelic mutations in the FANCD1/BRCA2 gene. Conclusion: We describe the first case of hepatoblastoma in a patient with FA to raise awareness of this tumour type in the close clinical observation of early cancer-prone forms of this condition, particularly in the presence of FANCD1/BRCA2 mutations. The present case also underscores the importance of FA testing in patients with VACTERL(-H).

Intestinal fluid secretion is pivotal in the creation of an ideal environment for effective enzymatic digestion, nutrient absorption and stool movement. Since fluid cannot be actively secreted into the gut, this process is dependent on an osmotic gradient, which is mainly created by chloride transport by the enterocyte. A pathological dysbalance between fluid secretion and absorption leads to obstruction or potentially fatal diarrhoea. This article reviews the widely accepted model of intestinal chloride secretion with an emphasis on the molecular players involved in this tightly regulated process.

The parietal cell is responsible for secreting concentrated hydrochloric acid into the gastric lumen. To fulfill this task, it is equipped with a broad variety of functionally coupled apical and basolateral ion transport proteins. The concerted scientific effort over the last years by a variety of researchers has provided us with the molecular identity of many of these transport mechanisms, thereby contributing to the clarification of persistent controversies in the field. This article will briefly review the current model of parietal cell physiology and ion transport in particular and will update the existing models of apical and basolateral transport in the parietal cell.

Many countries fail to use regional techniques for either labor analgesia or obstetric anesthesia. Kybele, an international outreach group, seeks to improve obstetric anesthesia practices worldwide. Its educational program in Croatia was evaluated by studying the change in use of regional anesthetic techniques in obstetrics after a Kybele visit.An international Kybele team spent two weeks in an educational program in Croatia in September 2005. Croatian anesthesiologists evaluated its benefit via a questionnaire two months after the program. In addition, hospitals that hosted a Kybele member compiled data on rates of regional blockade for cesarean section and labor analgesia before and after the Kybele visit.All Croatian anesthesiologists rated the overall experience as excellent or good. Eight out of nine hospitals contributed data to evaluate the program's impact on obstetric anesthesia practice. The average rate of use of regional anesthesia for cesarean section increased across the eight hospitals (P0.001) after Kybele; some institutions used neuraxial blockade for the majority of cesarean sections following the Kybele educational program. The average rate of epidural analgesia for labor also increased among the eight hospitals after the Kybele visit (P0.02), although absolute rates were still modest (maximum rate =5%).In Croatia, a two-week educational program in obstetric anesthesia increased the use of regional anesthesia and analgesia for labor and delivery in the year that followed the program. Multiple factors limit availability of analgesia for childbirth in Croatia.

InflatiBits is a modular construction kit that enables playful exploration of pneumatically actuated kinematic systems. The kit contains different building blocks based on soft robotics principles such as soft inflatable air-chambers, constraining elements, air-connectors, pressure sources, and sensor modules. The elements can be combined and actuated manually or through an optional Arduino-based control board. The board contains a motorized air-pump, solenoid valves and allows for connecting the sensor module to achieve more complex behaviors and motion patterns. The InflatiBits modules and connectors are compatible with standard Lego parts, enabling children to integrate them into existing playing environments.

Ein Forschungsprojekt mit dem Titel „Bewegung in der fruhen Kindheit“ eroffnet fachterminologisch ein weites Begriffsfeld. Schon die Benennung des Lebensabschnitts der fruhen Kindheit impliziert im padagogischen Anwendungsfeldeine Vielfalt von Begriffen, wie etwa Betreuung, Bildung, Forderung und Erziehung. Auch finden sich in den Bildungs- und Orientierungsplanen sowie in den Schul-, Fachschul- und Hochschulcurricula der Lander erganzend zum Begriff Bewegung - selten definiert oder nur unprazise beschrieben - die Begriffe Korper, Leib, Wahrnehmung, Gesundheit, Sport und Spiel wieder (siehe Bahr u. a. , in diesem Band). Eine Auseinandersetzung mit dem Gegenstands- und AnwendungsbereichBewegung, die Verortung von Bewegung im Kontext fruher Bildung sowie die Klarung daraus abgeleiteter Bildungsziele ist daher erforderlich und Ziel der folgenden Ausfuhrungen.

Bildung und Entwicklung erfolgen uber die Eigenaktivitat des Kindes. So ist nach Schafer „fruhkindliche Bildung in erster Linie Selbst-Bildung und wird entlang der Erfahrungen gewonnen, die Kinder in ihren Lebenszusammenhangen machen“ (2003, 31). Bewegungshandlungen werden damit zum Mittler von Entwicklungs- und Bildungsprozessen und die Art des raumlichen, materialen, personellen und interaktiven Gestaltungsprozesses durch die padagogische Fachkraft zu einer bedeutsamen didaktischen Kategorie (vgl. Fischer 2013, 22). Das Spannungsfeld zwischen „Struktur / Anleitung“ auf der einen und „Offenheit / Selbstbestimmung“ auf der anderen Seite ruckt dabei auch im Bildungsbereich Bewegung in den Fokus methodischer Uberlegungen. „Struktur“ ist dabei jedoch ebenso wenig mit „direkter Erziehung“ im Sinne angeleiteter expliziter und intentionaler Lernprozesse zu verstehen (vgl. Liegle 2010), wie „Offenheit“ mit dem Fehlen jeglicher padagogischer Einflussnahme gleichgesetzt werden kann.

Bewegung wird seit der Erarbeitung des Rahmen- und Orientierungsplans fur die fruhe Bildung in Kindertageseinrichtungen durch die Kultus- und Jugendministerkonferenz im Jahre 2004 als einer von sechs Bildungsbereichen in der fruhen Kindheit formuliert (KMK 2004) und ist seitdem in den Bildungsplanen und Empfehlungen fur Kindertagesstatten in allen Bundeslandern im Bildungsauftrag verankert.

Cystic fibrosis is a lethal genetic disorder commonly caused by the F508del mutation which is not amenable to gene therapy. Here, the authors use triplex-forming PNA molecules and donor DNA in biodegradable polymer nanoparticles to correct F508del and achieve clinically relevant levels of gene editing.