IgE autoantibodies in serum and skin of non-bullous and bullous pemphigoid patients

Background Non-bullous pemphigoid (NBP) is a pemphigoid variant which frequently resembles other pruritic skin diseases. In contrast with bullous pemphigoid (BP), blisters are absent. In BP, previous studies showed that IgE autoantibodies may be involved in its pathogenesis. IgE-activated mast cells, basophils and eosinophils may participate in BP by inducing pruritus and possibly blister formation, although the differential role of IgE in NBP compared with BP has not yet been described. Objective To assess IgE in serum and skin of NBP and BP patients. Methods We examined total IgE and pemphigoid-specific IgE in the serum of 68 NBP and 50 BP patients by enzyme-linked immunosorbent assay (ELISA). Sera of 25 pemphigus patients and 25 elderly patients with pruritus were included as controls. Skin biopsies of 14 NBP and 14 BP patients with the highest IgE titres to NC16A were stained for IgE by immunofluorescence techniques. Results Total IgE was elevated in 63% of NBP and 60% of BP patients, and in 20% of pemphigus controls, as well as 60% of elderly controls. IgE ELISAs were more frequently positive in BP than in NBP (NC16A 18% vs. 9%, P = 0.139; BP230 34% vs. 22%, P = 0.149). IgE ELISAs for NC16A and BP230 were positive in 8% and 20% of elderly controls, respectively, while all pemphigus controls were negative. Two of 28 biopsies (7%; one NBP, one BP) showed linear IgE along the basement membrane zone, while in most biopsies (71% NBP; 86% BP) IgE was bound to dermal cells. Conclusion Since IgE was present in the serum and skin of both NBP and BP patients, this supports IgE-dependent mechanisms common to both diseases, such as pruritus. However, it remains to be elucidated whether IgE contributes to blister formation in BP

Diagnostic accuracy of haemophilia early arthropathy detection with ultrasound (HEAD-US): A comparative magnetic resonance imaging (MRI) study

Background. Repeated haemarthroses affect approximately 90% of patients with severe haemophilia and lead to progressive arthropathy, which is the main cause of morbidity in these patients. Diagnostic imaging can detect even subclinical arthropathy changes and may impact prophylactic treatment. Magnetic resonance imagining (MRI) is generally the gold standard tool for precise evaluation of joints, but it is not easily feasible in regular follow-up of patients with haemophilia. The development of the standardized ultrasound (US) protocol for detection of early changes in haemophilic arthropathy (HEAD-US) opened new perspectives in the use of US in management of these patients. The HEAD-US protocol enables quick evaluation of the six mostly affected joints in a single study. The aim of this prospective study was to determine the diagnostic accuracy of the HEAD-US protocol for the detection and quantification of haemophilic arthropathy in comparison to the MRI. Patients and methods. The study included 30 patients with severe haemophilia. We evaluated their elbows, ankles and knees (overall 168 joints) by US using the HEAD-US protocol and compared the results with the MRI using the International Prophylaxis Study Group (IPSG) MRI score. Results. The results showed that the overall HEAD-US score correlated very highly with the overall IPSG MRI score (r = 0.92). Correlation was very high for the evaluation of the elbows and knees (r 48 0.95), and slightly lower for the ankles (r 48 0.85). Conclusions. HEAD-US protocol proved to be a quick, reliable and accurate method for the detection and quantification of haemophilic arthropathy

High-frequency irreversible electroporation (H-FIRE) for non-thermal ablation without muscle contraction

<p>Abstract</p> <p>Background</p> <p>Therapeutic irreversible electroporation (IRE) is an emerging technology for the non-thermal ablation of tumors. The technique involves delivering a series of unipolar electric pulses to permanently destabilize the plasma membrane of cancer cells through an increase in transmembrane potential, which leads to the development of a tissue lesion. Clinically, IRE requires the administration of paralytic agents to prevent muscle contractions during treatment that are associated with the delivery of electric pulses. This study shows that by applying high-frequency, bipolar bursts, muscle contractions can be eliminated during IRE without compromising the non-thermal mechanism of cell death.</p> <p>Methods</p> <p>A combination of analytical, numerical, and experimental techniques were performed to investigate high-frequency irreversible electroporation (H-FIRE). A theoretical model for determining transmembrane potential in response to arbitrary electric fields was used to identify optimal burst frequencies and amplitudes for <it>in vivo </it>treatments. A finite element model for predicting thermal damage based on the electric field distribution was used to design non-thermal protocols for <it>in vivo </it>experiments. H-FIRE was applied to the brain of rats, and muscle contractions were quantified via accelerometers placed at the cervicothoracic junction. MRI and histological evaluation was performed post-operatively to assess ablation.</p> <p>Results</p> <p>No visual or tactile evidence of muscle contraction was seen during H-FIRE at 250 kHz or 500 kHz, while all IRE protocols resulted in detectable muscle contractions at the cervicothoracic junction. H-FIRE produced ablative lesions in brain tissue that were characteristic in cellular morphology of non-thermal IRE treatments. Specifically, there was complete uniformity of tissue death within targeted areas, and a sharp transition zone was present between lesioned and normal brain.</p> <p>Conclusions</p> <p>H-FIRE is a feasible technique for non-thermal tissue ablation that eliminates muscle contractions seen in IRE treatments performed with unipolar electric pulses. Therefore, it has the potential to be performed clinically without the administration of paralytic agents.</p

Physics of the Riemann Hypothesis

Physicists become acquainted with special functions early in their studies. Consider our perennial model, the harmonic oscillator, for which we need Hermite functions, or the Laguerre functions in quantum mechanics. Here we choose a particular number theoretical function, the Riemann zeta function and examine its influence in the realm of physics and also how physics may be suggestive for the resolution of one of mathematics' most famous unconfirmed conjectures, the Riemann Hypothesis. Does physics hold an essential key to the solution for this more than hundred-year-old problem? In this work we examine numerous models from different branches of physics, from classical mechanics to statistical physics, where this function plays an integral role. We also see how this function is related to quantum chaos and how its pole-structure encodes when particles can undergo Bose-Einstein condensation at low temperature. Throughout these examinations we highlight how physics can perhaps shed light on the Riemann Hypothesis. Naturally, our aim could not be to be comprehensive, rather we focus on the major models and aim to give an informed starting point for the interested Reader.Comment: 27 pages, 9 figure

The KELT Follow-Up Network And Transit False-Positive Catalog: Pre-Vetted False Positives For TESS

The Kilodegree Extremely Little Telescope (KELT) project has been conducting a photometric survey of transiting planets orbiting bright stars for over 10 years. The KELT images have a pixel scale of ~23\u27\u27 pixel⁻¹—very similar to that of NASA\u27s Transiting Exoplanet Survey Satellite (TESS)—as well as a large point-spread function, and the KELT reduction pipeline uses a weighted photometric aperture with radius 3\u27. At this angular scale, multiple stars are typically blended in the photometric apertures. In order to identify false positives and confirm transiting exoplanets, we have assembled a follow-up network (KELT-FUN) to conduct imaging with spatial resolution, cadence, and photometric precision higher than the KELT telescopes, as well as spectroscopic observations of the candidate host stars. The KELT-FUN team has followed-up over 1600 planet candidates since 2011, resulting in more than 20 planet discoveries. Excluding ~450 false alarms of non-astrophysical origin (i.e., instrumental noise or systematics), we present an all-sky catalog of the 1128 bright stars (6 \u3c V \u3c 13) that show transit-like features in the KELT light curves, but which were subsequently determined to be astrophysical false positives (FPs) after photometric and/or spectroscopic follow-up observations. The KELT-FUN team continues to pursue KELT and other planet candidates and will eventually follow up certain classes of TESS candidates. The KELT FP catalog will help minimize the duplication of follow-up observations by current and future transit surveys such as TESS

A compilation of field surveys on gaseous elemental mercury (GEM) from contrasting environmental settings in Europe, South America, South Africa and China: separating fads from facts

Mercury is transported globally in the atmosphere mostly in gaseous elemental form (GEM, Hg0 gas), but still few worldwide studies taking into account different and contrasted environmental settings are available in a single publication. This work presents and discusses data from Argentina, Bolivia, Bosnia and Herzegovina, Brazil, Chile, China, Croatia, Finland, Italy, Russia, South Africa, Spain, Slovenia and Venezuela. We classified the information in four groups: (1) mining districts where this contaminant poses or has posed a risk for human populations and/or ecosystems; (2) cities, where the concentration ofatmospheric mercury could be higher than normal due to the burning of fossil fuels and industrial activities; (3) areas with natural emissions from volcanoes; and (4) pristine areas where no anthropogenic influence was apparent. All the surveys were performed using portable LUMEX RA-915 series atomic absorption spectrometers. The results for cities fall within a low GEM concentration range that rarely exceeds 30 ng m-3, that is, 6.6 times lower than the restrictive ATSDR threshold (200 ng m-3) for chronic exposure to this pollutant. We also observed this behavior in the former mercury mining districts, where few data were above 200 ng m-3.We noted that high concentrations of GEM are localized phenomena that fade away in short distances. However, this does not imply that they do not pose a risk for those working in close proximity to the source. This is the case of the artisanal gold miners that heat the Au–Hg amalgam to vaporize mercury. In this respect, while GEM can be truly regarded as a hazard, because of possible physical–chemical transformations into other species, it is only under these localized conditions, implying exposure to high GEM concentrations, which it becomes a direct risk for humans.Grants CGL2009-13171 and CTM2012-33918 from the Spanish Ministry of Economy and Competitiveness and PII1I09-0142- 4389 from theCastilla-LaMancha (Spain)RegionalGovernment.Published713-7346A. Monitoraggio ambientale, sicurezza e territorioJCR Journalrestricte