Age-dependent sensitization to the 7S-vicilin-like protein Cor a 11 from hazelnut (Corylus avellana) in a birch-endemic region

Background: Hazelnut (Corylus avellana) allergy exhibits age and geographically distinct sensitization patterns that have not yet been fully resolved. Objective: To study sensitization to Cor a 11 in different age groups of hazelnut-allergic patients and infants with atopic dermatitis (AD) sensitized to hazelnut in a birch-endemic region. Methods: Sera from 80 hazelnut-allergic patients, 33 infants under 1 year of age with AD (24 sensitized and 9 not sensitized to hazelnut), 32 healthy control individuals, and 29 birch pollen–allergic but hazelnut-tolerant individuals were tested for immunoglobulin (Ig) E reactivity to Cor a 11 by ImmunoCAP. IgE reactivity to Cor a 1.01, Cor a 1.04, Cor a 8, and Cor a 9 was studied by ISAC microarray. Results: Forty patients (22 preschool children, 10 schoolchildren, and 8 adults) with systemic reactions on consumption of hazelnut were sensitized to Cor a 11 (respective rates of 36%, 40%, and 12.5%). Forty patients (6 preschool children, 10 schoolchildren, and 24 adults) reported oral allergy syndrome but only 2 of them (of preschool age) were sensitized to Cor a 11. Two (8%) of the AD infants sensitized to hazelnut showed IgE reactivity to Cor a 11. This reactivity was not observed in any of the AD infants without sensitization to hazelnut, in any of the birch-pollen allergic patients without hazelnut allergy, or in any of the healthy control individuals. Conclusion: Sensitization to Cor a 11 in a birch-endemic region is predominantly found in children with severe hazelnut allergy, a finding that is consistent with observations concerning sensitization to Cor a 9

Frequency of occurrence of medication discrepancies and associated risk factors in cases of acute hospital admission

Background: Medication discrepancies are a common occurrence following hospital admission and carry the potential for causing harm. However, little is known about the potential risk factors involved in medication discrepancies. Objective: The objective of this study was to determine how frequently medication discrepancies occur and their associated risk factors, in patients hospitalized via the emergency department of the Spaarne Gasthuis Hospital, located in The Netherlands. Methods: This retrospective observational study examines 832 hospital admissions which took place between April 1st and June 30th, 2015. Medication reconciliation was performed within 24 hours of admission and medication discrepancies were registered. The primary outcome recorded in the study was the proportion of patients experiencing one or more medication discrepancies, as verified by the physician. As a secondary outcome, the association between these discrepancies and pre-specified variables was analyzed using univariate and multivariate logistic regression. Results: At least one medication discrepancy was found to have occurred with 97 of the 832 patients (11.7%), the most common discrepancies involving incorrect drug dose (44.9%) and omission of medication (36.4%). In the univariate analysis, age (OR=1.03 [95% CI 1.02:1.04] p<0.001) and number of pre-admission medications taken (OR=1.13 [95%CI 1.09:1.17] p<0.001) were revealed to be significantly associated with the risk of medication discrepancies. Sex, type of medical specialty, and surgical versus non-surgical specialty were found not to be significantly associated with discrepancies. In the multivariate analysis, both the number of pre-admission medications (OR=1.10 [95%CI 1.06:1.15] p<0.001) and age (OR=1.02 [95%CI 1.01:1.03] p=0.004) were independently associated with the risk of medication discrepancy. Conclusions: Of the total number of patients, 11.7% experienced one or more medication discrepancies following admission to the hospital. Elderly patients taking multiple drugs were found to be particularly at risk

Alternative Ii-independent antigen-processing pathway in leukemic blasts involves TAP-dependent peptide loading of HLA class II complexes

During HLA class II synthesis in antigen-presenting cells, the invariant chain (Ii) not only stabilizes HLA class II complexes in the endoplasmic reticulum, but also mediates their transport to specialized lysosomal antigen-loading compartments termed MIICs. This study explores an alternative HLA class II presentation pathway in leukemic blasts that involves proteasome and transporter associated with antigen processing (TAP)-dependent peptide loading. Although HLA-DR did associate with Ii, Ii silencing in the human class II-associated invariant chain peptide (CLIP)-negative KG-1 myeloid leukemic cell line did not affect total and plasma membrane expression levels of HLA-DR, as determined by western blotting and flow cytometry. Since HLA-DR expression does require peptide binding, we examined the role of endogenous antigen-processing machinery in HLA-DR presentation by CLIP− leukemic blasts. The suppression of proteasome and TAP function using various inhibitors resulted in decreased HLA-DR levels in both CLIP− KG-1 and ME-1 blasts. Simultaneous inhibition of TAP and Ii completely down-modulated the expression of HLA-DR, demonstrating that together these molecules form the key mediators of HLA class II antigen presentation in leukemic blasts. By the use of a proteasome- and TAP-dependent pathway for HLA class II antigen presentation, CLIP− leukemic blasts might be able to present a broad range of endogenous leukemia-associated peptides via HLA class II to activate leukemia-specific CD4+ T cells

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

Genetic and Environmental Influences on Individual Differences in Attitudes Toward Homosexuality: An Australian Twin Study

Previous research has shown that many heterosexuals hold negative attitudes toward homosexuals and homosexuality (homophobia). Although a great deal of research has focused on the profile of homophobic individuals, this research provides little theoretical insight into the aetiology of homophobia. To examine genetic and environmental influences on variation in attitudes toward homophobia, we analysed data from 4,688 twins who completed a questionnaire concerning sexual behaviour and attitudes, including attitudes toward homosexuality. Results show that, in accordance with literature, males have significantly more negative attitudes toward homosexuality than females and non-heterosexuals are less homophobic than heterosexuals. In contrast with some earlier findings, age had no significant effect on the homophobia scores in this study. Genetic modelling showed that variation in homophobia scores could be explained by additive genetic (36%), shared environmental (18%) and unique environmental factors (46%). However, corrections based on previous findings show that the shared environmental estimate may be almost entirely accounted for as extra additive genetic variance arising from assortative mating for homophobic attitudes. The results suggest that variation in attitudes toward homosexuality is substantially inherited, and that social environmental influences are relatively minor

Epidemiology and Molecular Relationships of Cryptosporidium spp. in People, Primates, and Livestock from Western Uganda

Cryptosporidium is a common gastrointestinal parasite known for its zoonotic potential. We found Cryptosporidium in 32.4% of people, 11.1% of non-human primates, and 2.2% of livestock in the region of Kibale National Park, Uganda. In people, infection rates were higher in one community than elsewhere, and fetching water from an open water source increased the probability of infection. Phylogenetic analyses identified clusters of Cryptosporidium with mixed host origins in people, primates, and livestock outside the park; however, parasites from primates inside the park were genetically divergent, suggesting a separate sylvatic transmission cycle. Infection was not associated with clinical disease in people, even in the case of co-infection with the gastrointestinal parasite Giardia duodenalis. Parasites such as Cryptosporidium may be maintained through frequent cross-species transmission in tropical settings where people, livestock, and wildlife interact frequently, but the parasite may undergo more host-specific transmission where such interactions do not occur. Persistent low-level shedding and immunity may limit the clinical effects of infection in such settings

Phase I and pharmacokinetic study of irinotecan in combination with R115777, a farnesyl protein transferase inhibitor

The aims of this study were to determine the maximum-tolerated dose (MTD), toxicity profile, and pharmacokinetics of irinotecan given with oral R115777 (tipifarnib), a farnesyl protein transferase inhibitor. Patients were treated with escalating doses of irinotecan with interval-modulated dosing of R115777 (continuously or on days 1-14, and repeated every 21 days). In total, 35 patients were entered onto the trial for a median duration of treatment of 43 days (range, 5-224 days). Neutropenia and thrombocytopenia were the dose-limiting toxicities; other side effects were mostly mild. The MTD was established at R115777 300 mg b.i.d. for 14 consecutive days with irinotecan 350 mg m-2 given every 3 weeks starting on day 1. Three patients had a partial response and 14 had stable disease. In the continuous schedule, the area under the curves of irinotecan and its active metabolite SN-38 were 20.0% (P = 0.004) and 38.0% (P < 0.001) increased by R115777, respectively. Intermittent dosing of R115777 at a dose of 300 mg b.i.d. for 14 days every 3 weeks is the recommended dose of R115777 in combination with the recommended single-agent irinotecan dose of 350 mg m-2