Background: The precise immunological mechanisms for the early clinical protection of venom immunotherapy (VIT) have not yet been explained. Our aim was to evaluate whether high-affinity IgE receptor ...(FcepsiRI) and the related basophil function have a role in the induction of short-term VIT protection. Methods: We included 60 adults and 48 children. Basophil threshold sensitivity (CD-sens) to anti-FcepsiRI stimulation, and FcepsiRI gene and cell-surface expression were assessed at the beginning and just before the first maintenance dose (MD) of 100 μg of ultra-rush VIT (day 5) and at the beginning, during buildup, and just before the first MD of 70 μg and of 100 μg of semi-rush VIT (weeks 1-2 and 5). Results: We demonstrated a significant reduction in CD-sens to anti-FcepsiRI stimulation before the first MD in both ultra-rush and semi-rush VIT in all included subjects. FcepsiRI gene and/or cell-surface expression was decreased in 34-100% of subjects, with different dynamics between VIT protocols. Conclusion: We found a marked desensitization of FcepsiRI-activated basophils after short-term VIT. This suppression, which could be highly relevant for the development of early protective mechanisms, might be also related to the changes at the level of FcepsiRI expression. PUBLICATION ABSTRACT
Ecological interactions, such as predation and bioturbation, are thought to be fundamental determinants of macroevolutionary trends. A data set containing global occurrences of Phanerozoic fossils of ...benthic marine invertebrates shows escalatory trends in the relative frequency of ecological groups, such as carnivores and noncarnivorous infaunal or mobile organisms. Associations between these trends are either statistically insignificant or interpretable as preservational effects. Thus, there is no evidence that escalation drives macroecological trends at global and million-year time scales. We also find that taxonomic richness and occurrence data are cross-correlated, which justifies the traditional use of one as a proxy of the other.
INTRODUCTION:
Radiation induced damage in glioblastoma (GB) patients can present in a late-delayed fashion as radiation necrosis (RN) or tumor recurrence (TR). The radiographic differentiation of ...these entities is particularly challenging as they appear similar on magnetic resonance imaging (MRI.) Failure to differentiate these can ultimately lead to unnecessary surgery and early cessation radiation therapy. There is a need for developing novel non-invasive techniques that can reliably distinguish between radiation necrosis and tumor recurrence.
METHODS:
We orthotopically transplanted GL261 mouse glioblastoma cells into C57BL/6 mice, with successful tumor induction verified by MRI after two weeks. To consistently induce RN/TR, an aggressive radiation dose fractionation (12 Gy/60 Gy) on alternating days was used. This was completed such that one portion of the tumor received 100% dose of radiation fraction, sufficient to cause RN, whereas the tumor edge received only 50% of the dose, allowing for tumor recurrence. At four time points, MRI and diffusion kurtosis imaging (DKI) were obtained, and objective metrics such as mean, axial, and radial kurtosis and diffusivity were calculated.
RESULTS:
Our data demonstrated mice tumor recurrence and radiation necrosis on MR imaging. MRI and DKI at 2 weeks following orthotopic glioblastoma implantation demonstrated edema and gyral edema compatible with tumor recurrence. One week later, imaging sequences demonstrated continued tumor progression. This demonstrated that our proposed model for radiation induction was effective at achieving its goal of creating some areas of RN and some of TR.
CONCLUSIONS:
Our results provides an invaluable platform for the mechanistic study of acute radiation necrosis, chronic radiation necrosis, and tumor recurrence, and management of these conditions.
Purpose: Pulmonary rehabilitation programs (PR) are an important part of the comprehensive treatment of patients with chronic pulmonary diseases. Patients respond individually to PR. The aim of this ...study is to identify potential predictors of success of PR to recognise patients who benefit most and to uncover possible reasons for poor response to PR. Patients and Methods: We included 121 patients with chronic obstructive pulmonary disease (COPD) who completed our 4-week inpatient PR without any exacerbations of disease during PR that could potentially affect PR outcomes. Improvement in distance of greater than or equal to 30 m on the 6-minute walk test (6MWT) after PR was chosen as a primary marker of physical success. Ninety-one patients achieved improvement of greater than or equal to 30 m on the 6MWT and were thus considered good responders, and 30 patients were poor responders with improvement in the distance of <30 m on the 6MWT. Results: We compared baseline clinical characteristics, medication, lung function, physical capacity, body composition, and laboratory blood tests between groups of good and poor responders. The most prominent differences between groups were associated with differences in baseline body composition and erythrocyte-related parameters. Good responders had significantly lower body water content (p = 0.042) and higher body weight (p = 0.036), body fat content (p = 0.049), dry lean mass (p = 0.021), haemoglobin levels (p = 0.040), erythrocyte count (p = 0.017), haematocrit (p = 0.030) and iron level (p = 0.028). Conclusion: A more muscular body composition and a higher ability to transport oxygen from the blood to the muscles could be beneficial for the outcome of PR. Plain Language Summary: Pulmonary rehabilitation programs (PR) are important part of management of patients with chronic obstructive pulmonary diseases and other chronic pulmonary diseases. Nevertheless, PR are sparsely available to patients, and patients respond to PR individually. Our study will help identify patients who benefit most from PR and find possible reasons why the physical condition of some patients does not improve with PR. Only patients with chronic obstructive pulmonary disease who completed inpatient pulmonary rehabilitation program without any exacerbations of disease that could potentially affect PR outcomes were included in this study to determine what baseline patient characteristics could predict good and poor responders to PR. The results of our study suggest that a more muscular body composition and a higher ability to transport oxygen from the blood to the muscles could be beneficial to the outcome of PR. We suggest that before sarcopenic or anaemic patients are referred for PR, special care should first be taken to address and remedy their condition to maximise their physical gain in PR. Keywords: pulmonary rehabilitation, COPD, predictors, responders
How does the choice of size metric, specimen selection, and taxonomic level affect the results of macroevolutionary or ecological analyses? Four molluscan data sets are used to address this question ...as follows. First, the relationships among various size metrics are examined using a morphometric data set of Late Cretaceous-Oligocene veneroid bivalves. Second, the relationship between the size of bulk-sampled specimens and the size of species' type specimens is examined using bulk-sampled bivalves and gastropods from the Coffee Sand (Upper Cretaceous, Mississippi). Third, the same relationship is examined using mollusk-dominated field censuses from the type Cincinnatian (Upper Ordovician, Ohio, Indiana, and Kentucky). Fourth, the relationship between the size of the type species of a genus and median species size is examined using literature-derived measurements of bivalve type specimens from the recent eastern Pacific continental shelf. Together these data sets provide estimates of the biases imposed by measuring different kinds of specimens and using different methods of estimating body size. The geometric mean of length and height is highly correlated with more complex morphometrically based metrics and is our preferred bivalve size metric. Bulk or randomly sampled specimens are significantly smaller than species' type specimens for the Cretaceous dataset but significantly larger for the Ordovician dataset. Genus' type-species size is an unbiased estimate of median species size. These results suggest that large-scale studies can use the size of the type species of a genus as an unbiased proxy for a type-specimen size of a genus' median species, but that species' type-specimen size is a biased proxy for bulk or randomly sampled specimens. In addition, this study emphasizes the importance of using a single type of measurement within studies and suggests that combining multiple types of specimens (e.g., type specimens and bulk-sampled specimens) could lead to substantive errors.
Background The identification of the disease-causing insect in venom allergy is often difficult. Objective To establish recombinant allergen-based IgE tests to diagnose bee and yellow jacket wasp ...allergy. Methods Sera from patients with bee and/or wasp allergy (n = 43) and patients with pollen allergy with false-positive IgE serology to venom extracts were tested for IgE reactivity in allergen extract-based tests or with purified allergens, including nonglycosylated Escherichia coli –expressed recombinant (r) Api m 1, rApi m 2, rVes v 5, and insect cell–expressed, glycosylated rApi m 2 as well as 2 natural plant glycoproteins (Phl p 4, bromelain). Results The patients with venom allergy could be diagnosed with a combination of E coli –expressed rApi m 1, rApi m 2, and rVes v 5 whereas patients with pollen allergy remained negative. For a group of 29 patients for whom the sensitizing venom could not be identified with natural allergen extracts, testing with nonglycosylated allergens allowed identification of the sensitizing venom. Recombinant nonglycosylated allergens also allowed definition of the sensitizing venom for those 14 patients who had reacted either with bee or wasp venom extracts. By IgE inhibition studies, it is shown that glycosylated Api m 2 contains carbohydrate epitopes that cross-react with natural Api m 1, Ves v 2, natural Phl p 4, and bromelain, thus identifying cross-reactive structures responsible for serologic false-positive test results or double-positivity to bee and wasp extracts. Conclusion Nonglycosylated recombinant bee and wasp venom allergens allow the identification of patients with bee and wasp allergy and should facilitate accurate prescription of venom immunotherapy.
The Mesozoic–Cenozoic transition is generally seen as a pivotal time in the evolution of benthic marine assemblages but the details of the timing and drivers of these changes are poorly known. The ...Atlantic and Gulf Coastal Plains of the United States contain assemblages preserved as original aragonitic and calcitic material in unconsolidated sediments. This makes coastal plain assemblages ideally suited to paleoecological analyses. Data derived from bulk samples of the Coffee Formation (lower/middle Campanian: Mississippi) as well as published faunal lists from comparable samples of the Severn (Maastrichtian: Maryland), Providence (Maastrichtian: Georgia and Alabama), Stone City (Eocene: Texas), and Gosport (Eocene: Alabama) Formations are used to assess changes in taxonomic diversity and ecomorphological group (life habit and trophic group) composition through this time interval. These analyses find a significant decrease in rarefied-sample species richness from the Campanian through the Eocene, but no change in evenness. With the notable exception of the Stone City Formation, increases in carnivore (neogastropod) richness and abundance occur before the Campanian. Epifaunal suspension-feeding species are a smaller proportion of the sample richness in Eocene samples than in Cretaceous samples. Decreased relative epifaunal suspension-feeder biomass but unchanged relative numbers of epifaunal suspension-feeder individuals suggests a relative decrease in epifaunal suspension-feeder size. Infaunal suspension feeders increase in richness and abundance through the interval. The proportion of drilled bivalves and gastropods does not change through the interval. Changes found in the structure of local shallow-shelf benthic assemblages from the Campanian through the Eocene are generally small relative to the variability between samples. Formation-level variation between assemblages is high relative to the magnitude of the temporal signal, emphasizing the need for investigators to include multiple formations per interval in tests of temporal trends.
Current guidelines for venom immunotherapy suggest that immunotherapy should be performed only in patients with IgE mediated systemic reactions. However, opinions on the diagnosis and treatment of ...patients with systemic reactions in the absence of IgE are quite varied. We present a patient with a history of atypical systemic reactions after a bee sting. Skin tests and specific IgE for bee venom were negative. We performed a sting provocation test in order to characterize the nature and mechanism of reaction. The provocation test was positive and mast cell activation was proved by tryptase elevation. We decided to treat the patient with immunotherapy. After beginning immunotherapy we were able to detect specific IgE for bee venom in the serum.
Purpose To search for the association between the –634 C/G polymorphism of the VEGF gene and vision threating proliferative diabetic retinopathy (PDR) and to determine whether vitreous levels of VEGF ...were affected by genetic factors.
Methods In this cross sectional case‐control study 349 unrelated Slovene subjects (Caucasians) with type 2 diabetes mellitus were enrolled: 206 patients with vision threating PDR in whom vitrectomy was performed, and the control group of 143 subjects with type 2 diabetes of duration of more than 10 years who had no clinical signs of diabetic retinopathy. In 68 out of 206 patients with PDR (71 eyes) vitreous fluid samples (0.3 ml) were obtained by vitreoretinal surgery.
Results The –634 C/G VEGF gene polymorphism was not associated with PDR. Moreover, significantly higher vitreous levels of VEGF were demonstrated in diabetics with the CC genotype compared to those with the other (CG + GG) genotypes.
Conclusion Despite the effect of the –634 C/G VEGF gene polymorphism on vitreous levels of VEGF in PDR, it failed to contribute to the genetic susceptibility to PDR.
