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Background: Aprepitant is a neurokinin 1 receptor (NK1R) antagonist used for its antipruritic properties in dermatoses and systemic diseases. The mode of action is still unclear. A peripheral effect is assumed as aprepitant shows efficacy in inflammatory skin diseases including prurigo nodularis (PN). Objectives: To investigate the peripheral effects of NK1R antagonism in PN and cell culture models. Methods: Subjects with PN received an aprepitant treatment. Clinical, morphological and immunohistochemical changes were investigated in skin biopsies before and after treatment. Expression of NK1R was analysed by immunohistochemistry and for downstream pathways ((p)ERK1/2) by Western blotting in PN patients and matched healthy volunteers. Effects of NK1R blocking were analysed in cell cultures of primary keratinocytes by Western blotting for (p)ERK1/2 and by qPCR for NK1R, interleukin (IL)‐1beta, IL‐6, IL‐8 and TNFalpha. Results: Aprepitant treatment showed significant reduction in pruritus intensity (P < 0.05) in PN and relevant immunohistochemical changes (down: CD5, CD25, up: CD79a, IL4). NK1R expression was higher in keratinocytes of PN patients compared to healthy controls. After treatment, epidermal NK1R expression increased while expression and activation of ERK1/2 decreased. In vitro, receptor up‐regulation and reduced expression and activation of ERK1/2 were confirmed and reduced IL‐expression shown when blocking NK1R. Conclusion: Our data confirm that NK1R antagonists such as aprepitant exhibit effects in the skin. Epidermal receptor expression, epidermal inflammatory ILs, ERK1/2 MAPK signalling and cutaneous inflammatory infiltrate were targets of NK1R antagonism. This may explain partly the antipruritic effect of NK1R antagonists next to its role in the central nervous system. Linked Commentary: J.Wallengren. J Eur Acad Dermatol Venereol 2019; 33: 2221–2222. https://doi.org/10.1111/jdv.16031. [ABSTRACT FROM AUTHOR]

Background: Although chronic pruritus affects a large part of the population, its reliable assessment remains difficult. Electronical diaries (eDiaries) are often used in multicentre clinical trials. The ItchApp© for Android was developed to assess itch intensity and course and was validated for the German language in 2017. Objective: To validate ItchApp© for the use in the Polish and US English languages. Methods: Fifty‐three subjects in Poland and thirty subjects in the USA with chronic pruritus completed the paper‐based and app‐based questionnaires. These questionnaires contained items for measuring the itch intensity, including a numerical rating scale (NRS) and verbal rating scale (VRS), and for detecting the change of pruritus since the beginning of treatment. Results: The ItchApp© showed a high level of test–retest reliability [Intraclass correlation, Kappa and Kendall‐Tau B coefficients: 0.915–1.000 (Poland) and 0.863–1.000 (USA)]. The convergent validity showed strong correlation between the itch intensity scales on the ItchApp© (Items II‐IV = VRS mean, NRS mean and NRS worst) and the paper‐based itch intensity scales (mean and worst: VRS, NRS, VAS) [Spearman‐Rho and Pearson correlation coefficients: 0.710–0.987 (Poland) and 0.646–0.954 (USA)]. The ItchApp© items moderately correlated with the ItchyQol scores [Spearman‐Rho and Pearson correlation coefficients: 0.303–0.554 (Poland) and 0.275–0.447 (USA)]. After completing the ItchApp© questionnaire, a feasibility questionnaire was completed and showed that subjects feel the app is well suited for assessing pruritus. Conclusion: We provide evidence for the ItchApp© as a validated eDiary for the assessment of pruritus in Polish and US English languages, enabling its use in multicentre international clinical trials. [ABSTRACT FROM AUTHOR]

Background: Currently available tools to monitor patients with chronic prurigo over time focus on pruritus and quality of life parameters, while no instrument objectively assessing the pruriginous lesions is yet available. Objective: The objective of this study was to develop a physician‐assessed Prurigo Activity Score (PAS), a new tool to monitor the distribution and activity of chronic prurigo lesions and to evaluate its reliability and validity. Methods: The 7‐item PAS questionnaire as well as validated pruritus intensity scales (VAS, NRS) and a skin‐related quality of life score (DLQI) were completed for 264 patients (172 females, age 61 years) at least twice over a period of 2 years. In addition, a 60‐min test–retest reliability test was performed by four experts for a random sample of 12 patients. Results: The PAS showed good test‐retest reliability (Cohens κ > 0.61; Cronbach‐alpha > 0.76), ordinal or metric items showed high inter‐rater reliability (Kendalls > 0.61) and items recording the number of lesions correlated significantly to each other (P < 0.001). The highest correlation to external constructs was achieved with DLQI. The feasibility test conducted by four raters indicated the suitability of PAS for tracking chronic prurigo in the clinical setting. Discussion: The PAS is a useful tool to objectively monitor pruriginous lesions in chronic prurigo patients over time. The sensitivity of change in the PAS score should be analysed in future studies. [ABSTRACT FROM AUTHOR]

The hydrogen exosphere constitutes the uppermost atmospheric layer of the Earth, and its shape may reflect the last stage of the atmospheric escape process. The distribution of hydrogen in the outer exosphere remains unobserved because outer geocoronal emissions are difficult to observe from within the exosphere. In this study, we used the Lyman Alpha Imaging Camera on board the Proximate Object Close Flyby with Optical Navigation spacecraft, located outside the exosphere, to obtain the first image of the entire geocorona that extends to more than 38 Earth radii. The observed emission intensity distribution can be reproduced using our analytical model that has three parameters: exobase temperature, exobase density, and solar radiation pressure, which implies that hot hydrogen production in the magnetized plasmasphere is not the dominant process shaping the outer hydrogen exosphere. However, the role of the magnetic effect in determining the total escape flux cannot be ruled out. [ABSTRACT FROM AUTHOR]

The Fukushima Daiichi nuclear power plant accident caused radioactive pollution by 131I, 134Cs and 137Cs. The surface of the ground was contaminated at a volume of 3 × 107 m3. The government has mandated that the top 5 cm of the contaminated soil be removed and stored, in this way, it is desirable to reduce its volume. Soil samples were collected from a mountain, a rice field and a vegetable field in northern Japan, and the silt was extracted from the muddy water by washing the soil. Next, the silt was sprayed with a solution of cesium carbonate (Cs2CO3). We determined the amounts of Al, Si, K and Cs in the silt particles using micro-particle-induced X-ray emission (micro-PIXE) analysis. The silt particles from a vegetable field, a rice field and a mountain were mainly formed from smectite or vermiculite, which absorbs Cs atoms. The measurements at multiple detection angles confirmed that Cs atoms were uniformly absorbed within silt particles less than in diameter. This resulted that the radioactive Cs atoms were adsorbed in silt particles within of the surface. [ABSTRACT FROM AUTHOR]

The charge dynamics in the double-layered quantum dot sensitized solar cell (QDSSC) was studied to clarify the reason why the cell performance was much improved by a double-layer coating, by using the heterodyne transient grating (HD-TG) and transient absorption methods, based on a previous study for a conventional QDSSC (N. Maeda et al., Phys. Chem. Chem. Phys., 2013, 15, 11006.) In the double-layered QDSSC, the layer order of CdS and CdSe affected the cell performance. When CdS is in between TiO2 and CdSe, the conversion efficiency was enhanced by 70%, while it was lowered by 50% in the opposite order. From the information on charge dynamics, it was found that electrons were efficiently injected to TiO2 by appropriate band alignment of CdS and CdSe, while only a part of the electrons were transferred to the TiO2 when the layer order was opposite. Furthermore, the reverse electron transfer does not matter for the conversion efficiency, because the process increased even for the appropriate layer order. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE Chronic heart failure (CHF) is associated with action potential prolongation and Ca2+ overload, increasing risk of ventricular tachyarrhythmias (VT). We therefore investigated whether ICa blockade was anti-arrhythmic in an intact perfused heart model of CHF. EXPERIMENTAL APPROACH CHF was induced in rabbits after 4 weeks of rapid ventricular pacing. Hearts from CHF and sham-operated rabbits were isolated and perfused (Langendorff preparation), with ablation of the AV node. VT was induced by erythromycin and low [K+] (1.5mM). Electrophysiology of cardiac myocytes, with block of cation currents, was simulated by a mathematical model. KEY RESULTS Repolarization was prolonged in CHF hearts compared with sham-operated hearts. Action potential duration (APD) and overall dispersion of repolarization were further increased by erythromycin (300 µM) to block IKr in CHF hearts. After lowering [K+] to 1.5mM, CHF and sham hearts showed spontaneous episodes of polymorphic non-sustained VT. Additional infusion of verapamil (0.75 µM) suppressed early afterdepolarizations (EAD) and VT in 75% of sham and CHF hearts. Verapamil shortened APD and dispersion of repolarization, mainly by reducing transmural dispersion of repolarization via shortening of endocardial action potentials. Mathematical simulations showed that EADs were more effectively reduced by verapamil assuming a state-dependent block than a simple block of ICa. CONCLUSIONS AND IMPLICATIONS Blockade of ICa was highly effective in suppressing VT via reduction of transmural dispersion of repolarization and suppression of EAD. Such blockade might represent a novel therapeutic option to reduce risk of VT in structurally normal hearts and also in heart failure. LINKED ARTICLE This article is commented on by Stams et al., pp. 554-556 of this issue. To view this commentary visit [ABSTRACT FROM AUTHOR]

Background: Molecular remodeling in heart failure includes slowing of repolarization, leading to proarrhythmia.Objective: To evaluate the effects of Na(+)/Ca(2+) exchanger (NCX) inhibition on repolarization as a novel antiarrhythmic concept in chronic heart failure (CHF).Methods and Results: CHF was induced by rapid ventricular pacing in rabbits. Left ventricular function was assessed by echocardiography. Monophasic action potentials (MAPs) showed a prolongation of repolarization in CHF after atrioventricular block and stimulation at different cycle lengths. Sotalol (100 μM, n = 13) or veratridine (0.5 μM; n = 15) resulted in a further significant increase in the MAP duration. CHF was associated with an increased dispersion of repolarization, as compared with sotalol-treated (+22 ± 7 ms; P < .05) and veratridine-treated (+20 ± 6 ms; P < .05) sham hearts. In the presence of a low potassium concentration, sotalol and veratridine reproducibly induced early afterdepolarizations (EADs) and polymorphic ventricular tachyarrhythmias (VTs). SEA0400 (1 μM), a pharmacological inhibitor of NCX, significantly shortened the MAP duration (P < .01) and reduced dispersion (P < .05). It suppressed EAD in 6 of 13 sotalol-treated failing hearts and in 9 of 10 veratridine-treated failing hearts, leading to a reduction in VT (60% in sotalol-treated failing hearts and 83% in veratridine-treated failing hearts). Simulations using a mathematical model showed a reduction in the action potential duration and the number of EADs by the NCX block in all subgroups.Conclusions: In an experimental model of CHF, the acute inhibition of NCX (1) reduces the MAP duration, (2) decreases dispersion of repolarization, and (3) suppresses EAD and VT. Our observations indicate for the first time that pharmacological NCX inhibition increases repolarization reserve and protects against VTs in heart failure. [ABSTRACT FROM AUTHOR]

Particle size distribution of activity was investigated with an impactor for airborne particles released from a pneumatic irradiation system of a research reactor. Airborne radioactivity released from the pneumatic tube of the reactor was identified as 24Na, 38Cl, and 56Mn and various fission products of which origin was uranium impurity in aluminum used in the part of the pneumatic tube. The AMAD (activity median aerodynamic diameter) of 24Na and 56Mn that were produced through (n, γ) reactions was ca. 1 µm, while that of fission products was ca. 0.4 µm. It was suggested that radioactive particles of ca. 1 µm were due to activation of aluminum dust in the pneumatic tube, and that the particles of ca. 0.4 µm were formed by attachment of recoiled fission products to radiation-induced airborne particles. [ABSTRACT FROM AUTHOR]

A rapid measurement method for aerosol particle size is required to clarify the formation mechanism of freshly-formed radioactive aerosols in accelerator rooms. A graded screen array (GSA) method only requires brief sampling. Therefore, the GSA method is suitable for the measurement of radioactive aerosols in the accelerator rooms. In this work, a conventional GSA was applied to measure the particle size distribution of an aerosol. An influence of the radioactive gas on the GSA measurement was found. The adsorption of radioactive gases resulted in a discrepancy between the results of the GSA method and those of the diffusion battery method. An improved GSA method was developed to measure the radioactive aerosol formed in the accelerator room. The adsorption was measured by the improved GSA, and the influence of the radioactive gas was eliminated. The result of the improved GSA showed fair agreement with that of the diffusion battery system. [ABSTRACT FROM AUTHOR]

Purpose: To retrospectively evaluate the long-term outcome of the bell-bottom technique for the endovascular repair of common iliac artery (CIA) aneurysms. Methods: Between September 2003 and September 2008, 89 patients (84 men; mean age 73.7+/-8.4 years) with aortic and CIA aneurysms were treated at 2 European centers with aortic extension cuffs or large iliac limbs that gave a bell-bottom configuration to the iliac portion of an aortoiliac stent-graft. The mean maximum aortic diameter was 65.7+/-12.3 mm (range 42-98), and the mean diameter of the treated CIA aneurysms was 22.1+/-3.0 mm (range 20-30). Results: Technical success was achieved in 97.8% (87/89). There was no early (<30-day) mortality, but 8 (8.9%) patients died (none aneurysm-related) during follow-up. Cumulative survival by Kaplan-Meier analysis was 96.3% at 1 year, 85.5% at 3 years, and 83.1% at 5 years. After a mean follow-up of 56.5 months, computed tomography documented 3 (3.4%) type I endoleaks: one proximal leak was treated by conversion to open repair, and the other 2 distal type I endoleaks were treated by implantation of an iliac extension. Two (2.2%) type II endoleaks were accompanied by an increase in the aneurysm diameter; one was treated by coil embolization of the inferior mesenteric artery and the other by conversion to open repair after repeated coil embolization. One patient underwent thrombectomy for iliac limb occlusion. The freedom from secondary intervention was 91.6% at 5 years. The mean maximum diameter of the CIA aneurysms showed no significant change over time (24.1+/-3 mm at 30 days and 23.4+/-4 mm at latest follow-up). Conclusion: Moderate-size CIA aneurysms (<30 mm) can be safely and effectively treated using the bell-bottom technique. The risk of distal type I endoleak is low. Iliac-related complications can be successfully treated by endovascular techniques. [ABSTRACT FROM AUTHOR]

Background: Long QT syndrome (LQTS) is associated with sudden cardiac death resulting from torsades de pointes (TdP), which are triggered by early afterdepolarizations (EADs). The cardiac Na(+)/Ca(2+) exchanger (NCX) has been suggested to work as a trigger for EADs.Objective: The purpose of this study was to test the hypothesis that inhibition of NCX with a newly developed selective NCX inhibitor (SEA0400) reduces TdP.Methods and Results: In 34 Langendorff-perfused rabbit hearts, the I(Kr)-blocker sotalol (100 microM; n = 18) as well as veratridine (0.5 microM; n = 16), an inhibitor of sodium channel inactivation, led to a significant increase in monophasic action potential (MAP) duration thereby mimicking LQTS2 and LQTS3. In bradycardic hearts, recordings of eight MAPs demonstrated an increased dispersion of repolarization (sotalol: 67%; veratridine: 89%; P <.05). After lowering of potassium concentration, sotalol (56%) and veratridine (63%) induced TdP. Perfusion with SEA0400 (1 microM) suppressed EADs in 15 of 16 sotalol hearts and in seven of 13 veratridine hearts. SEA0400 significantly shortened MAP duration and reduced dispersion of repolarization in both groups (P <.05). This reduced TdP incidence in the sotalol group (100%) and in the veratridine group (77%). To investigate the effects of NCX inhibition on the cellular level, we used a computer model of the rabbit ventricular myocyte. I(Na) and I(Kr) were modified to mimic the effects of veratridine and sotalol, respectively. Consistent with our in vitro experiments, reduction of NCX activity accelerated repolarization of the cellular action potential and prevented EADs.Conclusion: In an intact rabbit heart model of LQT2 and LQT3 as well as in a computer model of the rabbit cardiac myocyte, inhibition of NCX is effective in preventing TdP due to a suppression of EADs, a reversion of action potential prolongation, and a reduction of dispersion of repolarization. Our observations suggest a therapeutic benefit of selective NCX inhibition in LQTS. [ABSTRACT FROM AUTHOR]

Abstract The Borg (binder of Rho GTPases) family proteins interact with CDC42 and TC10 in a guanosine triphosphate (GTP)-dependent manner. We have isolated a full-length cDNA of the mouse Borg4 gene, which is a member of this family. Sequence analysis revealed that this gene encoded a putative 349-amino acid protein. By reverse transcription--coupled polymerase chain reaction (RTPCR) analysis, we observed that Borg4 was expressed ubiquitously in adult tissues. Additionally, we determined the entire cDNA sequence of the putative human Borg4 orthologue. By fluorescence in situ hybridization, mouse Borg4 and the putative human orthologue have been assigned to mouse chromosome lie and human chromosome 17q24-25, which has been described as syntenic to the mouse region. [ABSTRACT FROM AUTHOR]