The basophil activation test (BAT) has become a pervasive test for allergic response through the development of flow cytometry, discovery of activation markers such as CD63 and unique markers ...identifying basophil granulocytes. Basophil activation test measures basophil response to allergen cross‐linking IgE on between 150 and 2000 basophil granulocytes in <0.1 ml fresh blood. Dichotomous activation is assessed as the fraction of reacting basophils. In addition to clinical history, skin prick test, and specific IgE determination, BAT can be a part of the diagnostic evaluation of patients with food‐, insect venom‐, and drug allergy and chronic urticaria. It may be helpful in determining the clinically relevant allergen. Basophil sensitivity may be used to monitor patients on allergen immunotherapy, anti‐IgE treatment or in the natural resolution of allergy. Basophil activation test may use fewer resources and be more reproducible than challenge testing. As it is less stressful for the patient and avoids severe allergic reactions, BAT ought to precede challenge testing. An important next step is to standardize BAT and make it available in diagnostic laboratories. The nature of basophil activation as an ex vivo challenge makes it a multifaceted and promising tool for the allergist. In this EAACI task force position paper, we provide an overview of the practical and technical details as well as the clinical utility of BAT in diagnosis and management of allergic diseases.
The knowledge of how magnetization looks inside a ferromagnet is often hindered by the limitations of the available experimental methods which are sensitive only to the surface regions or limited in ...spatial resolution. Here we report a vector tomographic reconstruction based on soft X-ray transmission microscopy and magnetic dichroism data, which has allowed visualizing the three-dimensional magnetization in a ferromagnetic thin film heterostructure. Different non-trivial topological textures have been resolved and the determination of their topological charge has allowed us to identify a Bloch point and a meron-like texture. Our method relies only on experimental data and might be of wide application and interest in 3D nanomagnetism.
Rapamycin has long been considered an immunosuppressive agent due to its antiproliferative effects on immune cells, and is currently used as a component of antirejection regimens in transplantation. ...Despite the large number of mechanistic and clinical studies investigating the impact of rapamycin on cell‐mediated immunity, several paradoxes concerning rapamycin immunobiology remain. In particular, emerging evidence suggests that under certain circumstances rapamycin can exert immunostimulatory effects, boosting T cell responses in the face of pathogen infections and vaccines. Here, we review recent findings concerning the contradictory outcomes of rapamycin induced mTOR inhibition on CD4+ and CD8+ T cell responses in transplantation and protective immunity. These studies suggest that the conditions under which T cells are stimulated can profoundly modify the impact of rapamycin on antigen‐specific T cell responses. Thus, further investigation into the cellular and molecular pathways underlying the dichotomous effects of rapamycin in transplantation is required to harness the full potential of this immunomodulatory agent to promote graft survival and maximize protective immunity.
The authors review recent findings concerning the at times paradoxical effects of mTOR inhibition through rapamycin on CD4+ and CD8+ T cell responses in transplantation and protective immunity.
Nicotinamide adenine dinucleotide (NAD+) homeostasis is constantly compromised due to degradation by NAD+‐dependent enzymes. NAD+ replenishment by supplementation with the NAD+ precursors ...nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) can alleviate this imbalance. However, NMN and NR are limited by their mild effect on the cellular NAD+ pool and the need of high doses. Here, we report a synthesis method of a reduced form of NMN (NMNH), and identify this molecule as a new NAD+ precursor for the first time. We show that NMNH increases NAD+ levels to a much higher extent and faster than NMN or NR, and that it is metabolized through a different, NRK and NAMPT‐independent, pathway. We also demonstrate that NMNH reduces damage and accelerates repair in renal tubular epithelial cells upon hypoxia/reoxygenation injury. Finally, we find that NMNH administration in mice causes a rapid and sustained NAD+ surge in whole blood, which is accompanied by increased NAD+ levels in liver, kidney, muscle, brain, brown adipose tissue, and heart, but not in white adipose tissue. Together, our data highlight NMNH as a new NAD+ precursor with therapeutic potential for acute kidney injury, confirm the existence of a novel pathway for the recycling of reduced NAD+ precursors and establish NMNH as a member of the new family of reduced NAD+ precursors.
Our purpose is to adapt a statistical method for the analysis of discrete numerical series to the keywords appearing in scientific articles of a given area. As an example, we apply our methodological ...approach to the study of the keywords in the Library and Information Sciences (LIS) area. Our objective is to detect the new author keywords that appear in a fixed knowledge area in the period of 1 year in order to quantify the probabilities of survival for 10 years as a function of the impact of the journals where they appeared. Many of the new keywords appearing in the LIS field are ephemeral. Actually, more than half are never used again. In general, the terms most commonly used in the LIS area come from other areas. The average survival time of these keywords is approximately 3 years, being slightly higher in the case of words that were published in journals classified in the second quartile of the area. We believe that measuring the appearance and disappearance of terms will allow understanding some relevant aspects of the evolution of a discipline, providing in this way a new bibliometric approach.
The purpose of the present study was to investigate whether SNF472, the hexasodium salt of myo-inositol hexaphosphate (IP6 or phytate): 1. Inhibits induced calcification in cultured aortic valve ...interstitial cells (VIC) as an in vitro model of aortic valve stenosis and 2. Whether inhibition is different in VIC obtained from healthy and calcified aortic valves.
VIC from healthy (n = 5) and calcified (n = 7) human aortic valves were seeded in basic growth medium, osteogenic differentiation medium alone, or in osteogenic medium with SNF472 (3, 10, and 30 μM) and cultivated for 3 weeks. Calcification was quantified spectrophotometrically after Alizarin Red staining. In VIC from calcified valves, a complete inhibition of calcification was observed with SNF472 concentrations of 10 and 30 μM (p < .01), significantly stronger than in VIC from healthy valves. When SNF472 was added to VIC after 1 week in osteogenic medium, 30 and 100 μM SNF472 inhibited the progression of ongoing calcification by 81 and 100% (p < .01), respectively. The same concentrations of SNF472 given after 2 weeks reduced calcification by 35 and 40% respectively (not significant).
SNF472 inhibited both the formation and the progression of calcification with the strongest effect in VIC from calcified valves.
Display omitted
ABSTRACT
We use the data provided by the Gaia Early Data Release 3 to search for a highly complete volume-limited sample of unresolved binaries consisting of a white dwarf and a main-sequence ...companion (i.e. WDMS binaries) within 100 pc. We select 112 objects based on their location within the Hertzsprung–Russell diagram, of which 97 are new identifications. We fit their spectral energy distributions (SED) with a two-body fitting algorithm implemented in VOSA (Virtual Observatory SED Analyser) to derive the effective temperatures, luminosities, and radii (hence surface gravities and masses) of both components. The stellar parameters are compared to those from the currently largest catalogue of close WDMS binaries, from the Sloan Digital Sky Survey (SDSS). We find important differences between the properties of the Gaia and SDSS samples. In particular, the Gaia sample contains WDMS binaries with considerably cooler white dwarfs and main-sequence companions (some expected to be brown dwarfs). The Gaia sample also shows an important population of systems consisting of cool and extremely low-mass white dwarfs, not present in the SDSS sample. Finally, using a Monte Carlo population synthesis code, we find that the volume-limited sample of systems identified here seems to be highly complete (≃ 80 ± 9 per cent); however, it only represents ≃9 per cent of the total underlying population. The missing ≃91 per cent includes systems in which the main-sequence companions entirely dominate the SEDs. We also estimate an upper limit to the total space density of close WDMS binaries of ≃ (3.7 ± 1.9) × 10−4 pc−3.
The determination of salivary biomarkers as a means of monitoring general health and for the early diagnosis of disease is of increasing interest in clinical research. Based on the linkage between ...salivary proteins and systemic diseases, the aim of this work was the identification of saliva proteins using proteomics. Salivary proteins were separated using two‐dimensional (2‐D) gel electrophoresis over a pH range between 3–10, digested, and then analyzed by matrix assisted laser desorption/ionization‐time of flight (MALDI‐TOF)‐TOF mass spectrometry (MS) and tandem mass spectrometry (MS/MS). Proteins were identified using automated MS and MS/MS data acquisition. The resulting data were searched against a protein database using an internal Mascot search routine. Ninety spots give identifications with high statistical reliability. Of the identified proteins, 11 were separated and identified in saliva for the first time using proteomics tools. Moreover, three proteins that have not been previously identified in saliva, PLUNC, cystatin A, and cystatin B were identified.
A short, easy-to-use health status questionnaire is needed in the multidimensional assessment of chronic obstructive pulmonary disease (COPD) in routine practice. The performance of the eight-item ...COPD assessment test (CAT) was analysed in 1,817 patients from primary care in seven European countries. The CAT has a scoring range of 0-40 (high score representing poor health status). Mean CAT scores indicated significant health status impairment that was related to severity of airway obstruction, but within each Global Initiative for Obstructive Lung Disease stage (I to IV) there was a wide range of scores (I: 16.2 ± 8.8; II: 16.3 ± 7.9; III: 19.3 ± 8.2; and IV: 22.3 ± 8.7; I versus II, p = 0.88; II versus III, p<0.0001; III versus IV, p = 0.0001). CAT scores showed relatively little variability across countries (within ± 12% of the mean across all countries). Scores were significantly better in patients who were stable (17.2 ± 8.3) versus those suffering an exacerbation (21.3 ± 8.4) (p<0.0001); and in patients with no (17.3 ± 8.1) or one or two (16.6 ± 8.2) versus three or more (19.7 ± 8.5) comorbidities (p<0.0001 for both). The CAT distinguished between classes of other impairment measures and was strongly correlated with the St George's Respiratory Questionnaire (r = 0.8, p<0.0001). The CAT is a simple and easy-to-use questionnaire that distinguishes between patients of different degrees of COPD severity and appears to behave the same way across countries.
Display omitted
•High rate algae ponds removed efficiently most of the target pharmaceuticals.•Primary treatment did not influence the removal capacity of the HRAP systems.•Positive removals for ...non-biodegradable compounds were achieved.•Venlafaxine or O-desmethylvenlafaxine, usually recalcintrant in CAS, were removed.•Biomass samples were analised to perform a mass balance of the HRAP system.
The present study evaluates the removal capacity of two high rate algae ponds (HRAPs) to eliminate 12 pharmaceuticals (PhACs) and 26 of their corresponding main metabolites and transformation products. The efficiency of these ponds, operating with and without primary treatment, was compared in order to study their capacity under the best performance conditions (highest solar irradiance). Concentrations of all the target compounds were determined in both water and biomass samples. Removal rates ranged from moderate (40–60 %) to high (>60 %) for most of them, with the exception of the psychiatric drugs carbamazepine, the β-blocking agent metoprolol and its metabolite, metoprolol acid. O-desmethylvenlafaxine, despite its very low biodegradability in conventional wastewater treatment plants, was removed to certain extent (13–39 %). Biomass concentrations suggested that bioadsorption/bioaccumulation to microalgae biomass was decisive regarding the elimination of non-biodegradable compounds such as venlafaxine and its main metabolites. HRAP treatment with and without primary treatment did not yield significant differences in terms of PhACs removal efficiency. The implementation of HRAPs as secondary treatment is a feasible alternative to CAS in terms of overall wastewater treatment, including organic micropollutants, with generally higher removal performances and implying a green, low-cost and more sustainable technology.
PDF
