Angioedema is defined as localized and self‐limiting edema of the subcutaneous and submucosal tissue, due to a temporary increase in vascular permeability caused by the release of vasoactive ...mediator(s). When angioedema recurs without significant wheals, the patient should be diagnosed to have angioedema as a distinct disease. In the absence of accepted classification, different types of angioedema are not uniquely identified. For this reason, the European Academy of Allergy and Clinical Immunology gave its patronage to a consensus conference aimed at classifying angioedema. Four types of acquired and three types of hereditary angioedema were identified as separate forms from the analysis of the literature and were presented in detail at the meeting. Here, we summarize the analysis of the data and the resulting classification of angioedema.
The monoclonal anti‐immunoglobulin E (IgE) antibody, omalizumab, was the first drug approved for use in patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) who remain symptomatic despite ...H1‐antihistamine treatment. Omalizumab binds to free IgE, which lowers free IgE levels and causes FcεRI receptors on basophils and mast cells to be downregulated. It has been shown to improve symptoms of CIU/CSU, but its mechanism of action is not currently understood. Potential mechanisms in CIU/CSU include reducing mast cell releasability, reversing basopenia and improving basophil IgE receptor function, reducing activity of IgG autoantibodies against FcεRI and IgE, reducing activity of IgE autoantibodies against an antigen or autoantigen that has yet to be definitively identified, reducing the activity of intrinsically ‘abnormal’ IgE, and decreasing in vitro coagulation abnormalities associated with disease activity. However, none of these theories alone or in combination fully account for the pattern of symptom improvement seen with omalizumab therapy, and therefore, no one mechanism is likely to be the definitive mechanism of action. Additional research is needed to further clarify the involvement of omalizumab in relieving symptoms associated with the complex, multifactorial pathogenesis of CIU/CSU.
We introduce the antibody landscape, a method for the quantitative analysis of antibodymediated immunity to antigenically variable pathogens, achieved by accounting for antigenic variation among ...pathogen strains. We generated antibody landscapes to study immune profiles covering 43 years of influenza A/H3N2 virus evolution for 69 individuals monitored for infection over 6 years and for 225 individuals pre- and postvaccination. Upon infection and vaccination, titers increased broadly, including previously encountered viruses far beyond the extent of cross-reactivity observed after a primary infection. We explored implications for vaccination and found that the use of an antigenically advanced virus had the dual benefit of inducing antibodies against both advanced and previous antigenic clusters. These results indicate that preemptive vaccine updates may improve influenza vaccine efficacy in previously exposed individuals.
Background Although recurrence and death can occur in patients with papillary thyroid cancer (PTC) several years after being diagnosed, the necessary duration of follow-up for these patients remains ...unclear. Methods This was a single-institution, retrospective review of 269 patients with PTC. Cox proportional hazards model and Kaplan-Meier curves were used to identify risk factors for recurrence and death. Risk predictors included age, sex, radiation exposure history, extent of operation, radioactive iodine treatment, follicular variant of PTC (FVPTC), extrathyroidal invasion, multifocality, TNM status, and stage. Results Median follow-up was 27 years. Of 269 patients, 180 (66%) were female, and 196 (73%) were ≤45 years of age. Recurrence and cancer-specific death rates were 28% and 9%, respectively. Time to recurrence (±SD) was 8.1 (± 8.3) years and to cancer-specific death was 9.0 (± 11.0) years; however, 11% of recurrences and 17% of deaths occurred after 20 years. Risk factors for recurrence were older age, FVPTC, T4 tumors, cervical lymph node involvement, metastases, and stage ≥ 4a. Predictors of death from PTC were older age, metastases, and stage ≥ 3. Conclusion Both recurrences and death from PTC can occur more than 30 years after being treated, thus lifelong follow-up of patients with PTC is necessary.
Purpose
As life expectancy continues to rise, post-treatment health-related quality of life (HRQoL) of breast cancer patients becomes increasingly important. This study examined the one-year ...longitudinal relation between axillary treatments and physical, psychosocial, and sexual wellbeing and arm symptoms.
Methods
Women diagnosed with breast cancer who received different axillary treatments being axilla preserving surgery (APS) with or without axillary radiotherapy or full axillary lymph node dissection (ALND) with or without axillary radiotherapy were included. HRQoL was assessed at baseline, 6- and 12-months postoperatively using the BREAST-Q and the European Organization for Research and Treatment of Cancer QoL Questionnaire Breast Cancer Module (EORTC QLQ-BR23). Mixed regression models were constructed to assess the impact of axillary treatment on HRQoL. HRQoL at baseline was compared to HRQoL at 6- and at 12-months postoperatively.
Results
In total, 552 patients were included in the mixed regressions models. Except for ALND with axillary radiotherapy, no significant differences in physical and psychosocial wellbeing were found. Physical wellbeing decreased significantly between baseline and 6- and 12-months postoperatively (
p
< 0.001,
p
= 0.035) and psychosocial wellbeing decreased significantly between baseline and 12 months postoperatively (
p
= 0.028) for ALND with axillary radiotherapy compared to APS alone. Arm symptoms increased significantly between baseline and 6 months and between baseline and 12 months postoperatively for APS with radiotherapy (12.71, 13.73) and for ALND with radiotherapy (13.93, 16.14), with the lowest increase in arm symptoms for ALND without radiotherapy (6.85, 7.66), compared to APS alone (
p
< 0.05).
Conclusion
Physical and psychosocial wellbeing decreased significantly for ALND with radiotherapy compared to APS alone. Shared decision making and expectation management pre-treatment could be strengthened by discussing arm symptoms per axillary treatment with the patient.
Plain English summary
Breast cancer is one of the most common cancers among women worldwide. Since the survival rates are improving, the health-related quality of life of breast cancer patients after treatment becomes more important. One of the most important factors in the prognosis of breast cancer patients is the presence of axillary metastasis, the spread of breast cancer to lymph nodes in the armpit. There are different axillary treatments which can all affect health-related quality of life negatively. Therefore, the aim of this study is to examine the effect of different axillary treatments on physical, psychosocial, and sexual wellbeing and arm symptoms of breast cancer patients. This study included women with breast cancer who received either axillary preserving surgery with or without axillary radiotherapy, or a full axillary lymph node dissection with or without axillary radiotherapy. health-related quality of life was assessed with validated breast cancer specific questionnaires at baseline, 6- and 12-months postoperatively. Patients who underwent axilla preserving surgery without axillary radiotherapy experienced significantly less decline in both physical and psychosocial wellbeing as well as significantly fewer increase in arm symptoms compared to patients who received the more extensive axillary treatments. The results of this study can be used to improve shared decision making and expectation management for future breast cancer patients.b
Gravitationally bound three-body systems have been studied for hundreds of years and are common in our Galaxy. They show complex orbital interactions, which can constrain the compositions, masses and ...interior structures of the bodies and test theories of gravity, if sufficiently precise measurements are available. A triple system containing a radio pulsar could provide such measurements, but the only previously known such system, PSR B1620-26 (refs 7, 8; with a millisecond pulsar, a white dwarf, and a planetary-mass object in an orbit of several decades), shows only weak interactions. Here we report precision timing and multiwavelength observations of PSR J0337+1715, a millisecond pulsar in a hierarchical triple system with two other stars. Strong gravitational interactions are apparent and provide the masses of the pulsar MSymbol: see text(1.4378(13), where MSymbol: see textis the solar mass and the parentheses contain the uncertainty in the final decimal places) and the two white dwarf companions (0.19751(15)MSymbol: see text and 0.4101(3))MSymbol: see text, as well as the inclinations of the orbits (both about 39.2°). The unexpectedly coplanar and nearly circular orbits indicate a complex and exotic evolutionary past that differs from those of known stellar systems. The gravitational field of the outer white dwarf strongly accelerates the inner binary containing the neutron star, and the system will thus provide an ideal laboratory in which to test the strong equivalence principle of general relativity.
Methylation patterns of circulating cell-free DNA (cfDNA) contain rich information about recent cell death events in the body. Here, we present an approach for unbiased determination of the tissue ...origins of cfDNA, using a reference methylation atlas of 25 human tissues and cell types. The method is validated using in silico simulations as well as in vitro mixes of DNA from different tissue sources at known proportions. We show that plasma cfDNA of healthy donors originates from white blood cells (55%), erythrocyte progenitors (30%), vascular endothelial cells (10%) and hepatocytes (1%). Deconvolution of cfDNA from patients reveals tissue contributions that agree with clinical findings in sepsis, islet transplantation, cancer of the colon, lung, breast and prostate, and cancer of unknown primary. We propose a procedure which can be easily adapted to study the cellular contributors to cfDNA in many settings, opening a broad window into healthy and pathologic human tissue dynamics.
The regeneration of structural biopolymers into micelles or nanoparticles suspended in water has enabled the design of new materials with unique and compelling properties that can serve at the ...interface between the biotic and the abiotic worlds. In this study, we leveraged silk fibroin quintessential properties (i.e. polymorphism, conformability and hydrophobicity) to design a water-based protein suspension that self-assembles on the surface of food upon dip coating. The water-based post-processing control of the protein polymorphism enables the modulation of the diffusion of gases through the silk fibroin thin membranes (e.g. O2 and CO2 diffusion, water vapour permeability), which is a key parameter to manage food freshness. In particular, an increased beta-sheet content corresponds to a reduction in oxygen diffusion through silk fibroin thin films. By using the dip coating of strawberries and bananas as proof of principle, we have shown that the formation of micrometre-thin silk fibroin membranes around the fruits helps the management of postharvest physiology of the fruits. Thus, silk fibroin coatings enhance fruits' shelf life at room conditions by reducing cell respiration rate and water evaporation. The water-based processing and edible nature of silk fibroin makes this approach a promising alternative for food preservation with a naturally derived material.
We report the first discovery of a fast radio burst (FRB), FRB 20200125A, by the Green Bank Northern Celestial Cap (GBNCC) Pulsar Survey conducted with the Green Bank Telescope at 350 MHz. FRB ...20200125A was detected at a Galactic latitude of 58 43 with a dispersion measure of 179 pc cm3, while electron density models predict a maximum Galactic contribution of 25 pc cm3 along this line of sight. Moreover, no apparent Galactic foreground sources of ionized gas that could account for the excess DM are visible in multiwavelength surveys of this region. This argues that the source is extragalactic. The maximum redshift for the host galaxy is zmax = 0.17, corresponding to a maximum comoving distance of approximately 750 Mpc. The measured peak flux density for FRB 20200125A is 0.37 Jy, and we measure a pulse width of 3.7 ms, consistent with the distribution of FRB widths observed at higher frequencies. Based on this detection and assuming a Euclidean flux density distribution of FRBs, we calculate an all-sky rate at 350 MHz of FRBs sky−1 day−1 above a peak flux density of 0.42 Jy for an unscattered pulse having an intrinsic width of 5 ms, consistent with rates reported at higher frequencies, albeit with large uncertainties. Given the recent improvements in our single-pulse search pipeline, we also revisit the GBNCC survey sensitivity to various burst properties. Finally, we find no evidence of strong interstellar scattering in FRB 20200125A, adding to the growing evidence that some FRBs have circumburst environments where free-free absorption and scattering are not significant.
We report the synthesis and characterization of a new sulfur-containing derivative of bacteriochlorophyll
a
. The latter was isolated from biomass of the nonsulfur purple bacterium
Rhodobacter ...capsulatus
strain B10. The developed photosensitizer is
N
-aminobacteriopurpurinimide with an exocyclic amino group acylated with a lipoic acid moiety, which is a biogenic substance that acts as a cofactor of the pyruvate dehydrogenase and α-ketoglutarate dehydrogenase complexes in the body. The disulfide moiety of lipoic acid confers the compound aurophilicity, thus allowing its conjugation with gold nanoparticles (NP-Au) via S—Au bonds. The shape and the size of the resulting nanoconjugate with immobilized photosensitizer (PS—Au) were assessed by dynamic light scattering and transmission electron microscopy. The conjugated nanoparticles are spherical with hydrodynamic diameter of 100–110 nm. The PS—Au conjugate absorbs light at 824 nm and emits strong fluorescence at 830 nm, which allowed
in vivo
study of its dynamic biodistribution in rats bearing sarcoma M-1. Compared to the free photosensitizer, PS loaded on the gold nanoparticles (PS—Au) showed extended circulation time in the blood and enhanced tumor uptake due to nonspecific passive targeting when the drug accumulates in tumor sites through the leaky tumor neovasculature and does not return to the circulation.
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