bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor necrosis factor family member LIGHT acts with IL‐1β and TGF‐β to promote airway remodeling during rhinovirus infection
Authors: Mehta A. K. , Doherty T. , Broide D. , Croft M. 
Published: January 2018

AbstractBackgroundRhinovirus (RV) can exacerbate allergen‐driven asthma. However, it has been suggested that serial infections with RV may also lead to asthma‐like features in childhood without prior allergen exposure.AimWe sought to test the effects of RV infection in the absence of allergen challenge on lung tissue remodeling and to understand whether RV induced factors in common with allergen that promote remodeling.MethodsWe infected C57BL/6 mice multiple times with RV in the absence or presence of allergen to assess airway remodeling. We used knockout mice and blocking reagents to determine the participation of LIGHT (TNFSF14), as well as IL‐1β and TGF‐β, each previously shown to contribute to lung remodeling driven by allergen.ResultsRecurrent RV infection without allergen challenge induced an increase in peribronchial smooth muscle mass and subepithelial fibrosis. Rhinovirus (RV) induced LIGHT expression in mouse lungs after infection, and alveolar epithelial cells and neutrophils were found to be potential sources of LIGHT. Accordingly, LIGHT‐deficient mice, or mice where LIGHT was neutralized, displayed reduced smooth muscle mass and lung fibrosis. Recurrent RV infection also exacerbated the airway remodeling response to house dust mite allergen, and this was significantly reduced in LIGHT‐deficient mice. Furthermore, neutralizing IL‐1β or TGF‐β also limited subepithelial fibrosis and/or smooth muscle thickness induced by RV.ConclusionRhinovirus can promote airway remodeling in the absence of allergen through upregulating common factors that also contribute to allergen‐associated airway remodeling.
Isolation of a high‐affinity Bet v 1‐specific IgG‐derived ScFv from a subject vaccinated with hypoallergenic Bet v 1 fragments
Authors: Gadermaier E. , Marth K. , Lupinek C. , Campana R. , Hofer G. , Blatt K. , Smiljkovic D. , Roder U. , Focke‐Tejkl M. , Vrtala S. , Keller W. , Valent P. , Valenta R. , Flicker S. 
Published: January 2018

AbstractBackgroundRecombinant hypoallergenic allergen derivatives have been used in clinical immunotherapy studies, and clinical efficacy seems to be related to the induction of blocking IgG antibodies recognizing the wild‐type allergens. However, so far no treatment‐induced IgG antibodies have been characterized.ObjectiveTo clone, express, and characterize IgG antibodies induced by vaccination with two hypoallergenic recombinant fragments of the major birch pollen allergen, Bet v 1 in a nonallergic subject.MethodsA phage‐displayed combinatorial single‐chain fragment (ScFv) library was constructed from blood of the immunized subject and screened for Bet v 1‐reactive antibody fragments. ScFvs were tested for specificity and cross‐reactivity to native Bet v 1 and related pollen and food allergens, and epitope mapping was performed. Germline ancestor genes of the antibody were analyzed with the ImMunoGeneTics (IMGT) database. The affinity to Bet v 1 and cross‐reactive allergens was determined by surface plasmon resonance measurements. The ability to inhibit patients’ IgE binding to ELISA plate‐bound allergens and allergen‐induced basophil activation was assessed.ResultsA combinatorial ScFv library was obtained from the vaccinated donor after three injections with the Bet v 1 fragments. Despite being almost in germline configuration, ScFv (clone H3‐1) reacted with high affinity to native Bet v 1 and homologous allergens, inhibited allergic patients’ polyclonal IgE binding to Bet v 1, and partially suppressed allergen‐induced basophil activation.ConclusionImmunization with unfolded hypoallergenic allergen derivatives induces high‐affinity antibodies even in nonallergic subjects which recognize the folded wild‐type allergens and inhibit polyclonal IgE binding of allergic patients.
Oral myeloid cells uptake allergoids coupled to mannan driving Th1/Treg responses upon sublingual delivery in mice
Authors: Soria I. , López‐Relaño J. , Viñuela M. , Tudela J.‐I. , Angelina A. , Benito‐Villalvilla C. , Díez‐Rivero C. M. , Cases B. , Manzano A. I. , Fernández‐Caldas E. , Casanovas M. , Palomares O. , Subiza J. L. 
Published: January 2018

AbstractBackgroundPolymerized allergoids coupled to nonoxidized mannan (PM‐allergoids) may represent novel vaccines targeting dendritic cells (DCs). PM‐allergoids are better captured by DCs than native allergens and favor Th1/Treg cell responses upon subcutaneous injection. Herein we have studied in mice the in vivo immunogenicity of PM‐allergoids administered sublingually in comparison with native allergens.MethodsThree immunization protocols (4‐8 weeks long) were used in Balb/c mice. Serum antibody levels were tested by ELISA. Cell responses (proliferation, cytokines, and Tregs) were assayed by flow cytometry in spleen and lymph nodes (LNs). Allergen uptake was measured by flow cytometry in myeloid sublingual cells.ResultsA quick antibody response and higher IgG2a/IgE ratio were observed with PM‐allergoids. Moreover, stronger specific proliferative responses were seen in both submandibular LNs and spleen cells assayed in vitro. This was accompanied by a higher IFNγ/IL‐4 ratio with a quick IL‐10 production by submandibular LN cells. An increase in CD4+CD25highFOXP3+ Treg cells was detected in LNs and spleen of mice treated with PM‐allergoids. These allergoids were better captured than native allergens by antigen‐presenting (CD45+MHC‐II+) cells obtained from the sublingual mucosa, including DCs (CD11b+) and macrophages (CD64+). Importantly, all the differential effects induced by PM‐allergoids were abolished when using oxidized instead of nonoxidized PM‐allergoids.ConclusionOur results demonstrate for the first time that PM‐allergoids administered through the sublingual route promote the generation of Th1 and FOXP3+ Treg cells in a greater extent than native allergens by mechanisms that might well involve their better uptake by oral antigen‐presenting cells.
Immunoprofile of α‐Gal‐ and B‐antigen‐specific responses differentiates red meat‐allergic patients from healthy individuals
Authors: Apostolovic D. , Rodrigues R. , Thomas P. , Starkhammar M. , Hamsten C. , van Hage M. 
Published: January 2018

AbstractBackgroundThe galactose‐α‐1,3‐galactose (α‐Gal) epitope is involved in red meat allergy. As α‐Gal is structurally similar to the blood group B‐antigen, we explored the relationship between the immune responses to α‐Gal‐ and the B‐antigen in red meat‐allergic patients compared to healthy A/O or B blood donors.MethodsSera from 51 red meat‐allergic patients IgE‐positive to α‐Gal and 102 healthy blood donors (51 blood group A/O; 51 blood group B) were included. α‐Gal‐ and B‐antigen‐specific IgE (ImmunoCAP) and IgG/IgG1‐4 (ELISA) responses were determined. Basophil activation tests were performed.ResultsFifteen healthy donors were IgE positive to α‐Gal, of which 3 had blood group B. The allergic patients had significantly higher α‐Gal IgE levels compared to the healthy donors. The majority of the allergic patients, but none of the healthy donors, had IgE against the B‐antigen. Inhibition studies revealed cross‐reactivity between α‐Gal and the B‐antigen. The biological activity of the B‐antigen was confirmed by basophil activation tests. Anti‐α‐Gal IgG1 and IgG4 levels were significantly higher in the patients compared to the healthy donors. Moreover, the IgG response to the B‐antigen was comparable between the allergic patients and healthy A/O donors.ConclusionRed meat‐allergic patients showed significantly higher α‐Gal IgE, IgG1, and IgG4 levels, reflecting a Th2 response, compared to healthy blood donors. Blood group B donors had significantly reduced antibody responses to α‐Gal, due to similarities with the B‐antigen, resulting in a lower risk of sensitization to α‐Gal and development of red meat allergy.
Skin inflammation exacerbates food allergy symptoms in epicutaneously sensitized mice
Authors: Kawasaki A. , Ito N. , Murai H. , Yasutomi M. , Naiki H. , Ohshima Y. 
Published: January 2018

AbstractBackgroundCutaneous exposure to food antigen through impaired skin barrier has been shown to induce epicutaneous sensitization, thereby causing IgE‐mediated food allergies.ObjectiveWe examined whether skin barrier impairment following epicutaneous sensitization exacerbates food allergies.MethodsBALB/c mice were epicutaneously sensitized by repeated application of ovalbumin (OVA) to MC903‐pretreated ear skin for 48 hours weekly and then intragastrically challenged with OVA. After the first oral challenge, the skin barrier was disrupted with topical application of MC903 or by tape‐stripping. Mice were monitored for changes in body temperature and the occurrence of diarrhea after undergoing the second oral challenge. Serum levels of mouse mast cell protease‐1 (mmcp1) and OVA‐specific IgE, IgG1, IgG2a antibodies and OVA‐specific IgA levels in intestinal lavage fluid were measured by ELISA. Tissue accumulation of eosinophils was determined histologically.ResultsEpicutaneously sensitized mice developed anaphylaxis after intragastric challenge, as evidenced by diarrhea, decreased body temperature, and increased serum mmcp1 levels. Skin barrier disruption by MC903 treatment or tape‐stripping exacerbated allergic reactions induced by oral challenge. MC903 treatment increased serum baseline and postchallenge mmcp1 levels. Topical pretreatment with dexamethasone alleviated allergic reactions that were exacerbated by MC903 treatment.ConclusionEven after eliminating exposure to the antigen, inflammation from skin barrier disruption can exacerbate the severity of food allergy symptoms. Serum baseline mmcp1 levels might be an effective marker for predicting the severity of antigen‐induced allergic symptoms.
Transrectal prostate biopsy sepsis rate following reduced quinolone antibiotic prophylaxis from six doses to single dose
Authors: Bangash Haider K. , Hawks Cynthia , McCombie Steve P. , Brown Matthew , Hayne Dickon 
Published: January 2018

BackgroundThis study aimed to evaluate the rates of infective complication related to transrectal prostate biopsy (TRPB) as our centre changed its protocol from six doses over 3 days to a single pre‐procedure prophylactic dose.MethodsThis prospective cohort study identified infective complication in patients who attended and subsequently underwent TRPB at the time of their one‐stop prostate clinic at our public tertiary hospital between August 2011 and April 2017. Patients who underwent TRPB between August 2011 and November 2014 received six doses of 500 mg of ciprofloxacin, taken twice daily over 3 days. This protocol was changed to a single dose of 500 mg of ciprofloxacin prior to biopsy from February 2015 to April 2017. Patients who had travelled to South East Asia in the 6 months prior to TRPB received a single dose of 1 g intravenous ertapenem prior to biopsy, and this remained unchanged throughout the study period. The rates of infective complication were recorded and compared between the groups of patients who had undergone six doses versus a single dose of prophylactic ciprofloxacin.ResultsA total of 766 patients underwent TRPB from August 2011 to April 2017. Of these, 357 patients received the 3‐day course of prophylaxis (Group 1) and 409 patients received the single dose prophylaxis (Group 2). Fifty‐five patients were excluded from analysis. There was no significant difference in infective complications between the two groups (3.4% (11/326) Group 1 versus 4.9% (19/385) Group 2, P = 0.40).ConclusionOur study supports the use of a single dose of ciprofloxacin as sufficient antibiotic prophylaxis prior to TRPB.
Robotic‐assisted radical cystectomy with intracorporeal urinary diversion versus open: early Australian experience
Authors: Chow Ken , Zargar Homayoun , Corcoran Niall M. , Costello Anthony J. , Peters Justin S. , Dundee Philip 
Published: January 2018

BackgroundThe aim of this study was to describe our initial Australian single surgeon experience with robotic‐assisted radical cystectomy (RARC) and intracorporeal urinary diversion (ICUD) and to compare the outcomes with open radical cystectomy (ORC).MethodsBetween January 2014 and June 2016, consecutive patients diagnosed with muscle invasive and high‐risk non‐muscle invasive bladder cancer undergoing radical cystectomy were included. Treatment modalities included either RARC with ICUD or ORC. ICUD consisted of either intracorporeal ileal conduit or orthotopic neobladder formation. Prospectively collected perioperative and oncological outcomes were analysed.ResultsTwenty‐six RARC and 13 ORC were performed. Median operating times were 362 and 240 min for RARC and ORC, respectively (P < 0.001). Estimated blood loss for RARC was 300 mL compared with 500 mL for ORC (P = 0.01). Post‐operative haemoglobin drop was less in the RARC cohort (20% versus 24%, P = 0.03). There was no statistical difference in overall 90‐day complication rates (81% versus 62%, P = 0.25) and 90‐day major complication rates (19% versus 23%, P = 0.67) between the RARC and ORC groups, respectively. Positive surgical margins for RARC were 4% and 8% for ORC (P = 1.0).ConclusionEarly results demonstrate that the safe introduction of RARC with ICUD in Australia is potentially feasible without compromising perioperative and oncological outcomes. Future randomized trial with larger numbers will be required for further analysis in the Australian setting.
Five‐country manikin study found that neonatologists preferred using the LISAcath rather than the Angiocath for less invasive surfactant administration
Authors: Fabbri Laura , Klebermass‐Schrehof Katrin , Aguar Marta , Harrison Catherine , Gulczyńska Ewa , Santoro Debora , Di Castri Marco , Rigo Vincent 
Published: January 2018

AbstractAimLess invasive surfactant administration (LISA) has been shown to decrease the risk of death and bronchopulmonary dysplasia in preterm neonates. The LISAcath is the first catheter to be specifically developed for LISA, and we compared the clinical impressions of neonatologists using the LISAcath and the commonly used Angiocath in a simulated setting.MethodsThis was a multinational, multicentre study, conducted in October 2016, which involved 39 neonatologists who were recruited by employees of the sponsor from large, well‐recognised neonatal intensive care units across Europe. LISA was not the standard of care in these units in Austria, Belgium, Poland, Spain and the United Kingdom at the time of the study. After training, participants simulated LISA on a neonatal manikin, once with the LISAcath and once with Angiocath, then answered a 10‐item questionnaire.ResultsThe responses to nine of 10 questions showed that 67‐95% of the respondents preferred the LISAcath to the Angiocath, with most of the remainder indicating no preference. The only exception was the luer connection question, with two‐thirds expressing no preference. The LISAcath was considered potentially safer by 33 of 39 participants, with no votes for the Angiocath.ConclusionOverall, neonatologists preferred using the LISAcath rather than the Angiocath on a neonatal manikin.
The effects of income transfers on poverty reduction in people with disabilities in South Korea
Authors: Lee Ji Sun , Choi Jeong‐Kyun 
Published: January 2018

Using a nationally representative sample dataset from the 2016 Korean Welfare Panel Study, we examined the anti‐poverty effects of income transfers in people with disabilities. Our findings indicate that in households with a person with a disability, income transfers decreased by 55.9% and 84.8% of the pre‐transfer poverty rate and poverty gap, respectively. Before income transfers, households with a person with a disability were 1.94 times more likely to be poor compared to those without a person with a disability. When income transfers were offered, the chance of being poor in the disability group was only 1.11 times higher than that in the non‐disability group. Findings from the aggregated data suggest that means‐tested income transfers were more effective in reducing poverty levels than social insurance or private income transfers. At the individual level, the provision of means‐tested programs was also more likely to decrease the likelihood of experiencing poverty than social insurance and private income transfers.
Do final‐year medical students have sufficient prescribing competencies? A systematic literature review
Authors: Brinkman David J. , Tichelaar Jelle , Graaf Sanne , Otten René H. J. , Richir Milan C. , van Agtmael Michiel A. 
Published: January 2018

AimsPrescribing errors are an important cause of patient safety incidents and are frequently caused by junior doctors. This might be because the prescribing competence of final‐year medical students is poor as a result of inadequate clinical pharmacology and therapeutic (CPT) education. We reviewed the literature to investigate which prescribing competencies medical students should have acquired in order to prescribe safely and effectively, and whether these have been attained by the time they graduate.MethodsPubMed, EMBASE and ERIC databases were searched from the earliest dates up to and including January 2017, using the terms ‘prescribing’, ‘competence’ and ‘medical students’ in combination. Articles describing or evaluating essential prescribing competencies of final‐year medical students were included.ResultsTwenty‐five articles describing, and 47 articles evaluating, the prescribing competencies of final‐year students were included. Although there seems to be some agreement, we found no clear consensus among CPT teachers on which prescribing competencies medical students should have when they graduate. Studies showed that students had a general lack of preparedness, self‐confidence, knowledge and skills, specifically regarding general and antimicrobial prescribing and pharmacovigilance. However, the results should be interpreted with caution, given the heterogeneity and methodological weaknesses of the included studies.ConclusionsThere is considerable evidence that final‐year students have insufficient competencies to prescribe safely and effectively, although there is a need for a greater consensus among CPT teachers on the required competencies. Changes in undergraduate CPT education are urgently required in order to improve the prescribing of future doctors.
Pharmacokinetic–pharmacodynamic modelling of neutrophil response to G‐CSF in healthy subjects and patients with chemotherapy‐induced neutropenia
Authors: Melhem Murad , Delor Isabelle , Pérez‐Ruixo Juan Jose , Harrold John , Chow Andrew , Wu Liviawati , Jacqmin Philippe 
Published: January 2018

AimThe objective of the present study was to use pharmacokinetic–pharmacodynamic modelling to characterize the effects of chemotherapy on the granulopoietic system and to predict the absolute neutrophil counts (ANCs) for patients with chemotherapy‐induced neutropenia treated with filgrastim and pegfilgrastim.MethodsData were extracted from 10 phase I–III studies conducted in 110 healthy adults, and 618 adult and 52 paediatric patients on chemotherapy following administration of filgrastim or pegfilgrastim. The structural model accounted for ANC dynamics and the effects of filgrastim and pegfilgrastim, chemotherapy and corticosteroids. The impact of neutrophils on drug disposition was based on a drug receptor–binding model that assumed quasi‐equilibrium and stimulation of the production and maturation of neutrophils upon treatment. The chemotherapy and corticosteroid effects were represented by kinetic–pharmacodynamic‐type models, where chemotherapy stimulated elimination of neutrophil precursors at the mitotic stage, and corticosteroids stimulated neutrophil production.ResultsThe systemic half‐lives of filgrastim (2.6 h) and pegfilgrastim (10.1 h) were as expected. The effective half‐life of chemotherapy was 9.6 h, with a 2‐day killing effect. The rate of receptor elimination from mitotic compartments exhibited extreme interindividual variability (% coefficient of variation >200), suggesting marked differences in sensitivity to chemotherapy effects on ANCs. The stimulatory effects of pegfilgrastim were significantly greater than those of filgrastim. Model qualification confirmed the predictive capability of this model.ConclusionThis qualified model simulates the time course of ANC in the absence or presence of chemotherapy and predicts nadir, time to nadir and time of recovery from different grades of neutropenia upon treatment with filgrastim and pegfilgrastim.
Teicoplanin anaphylaxis associated with surgical prophylaxis
Authors: Azamgarhi Tariq , Shah Ashik , Warren Simon 
Published: January 2018

AimsThe aim of this paper is to determine the rate of true anaphylaxis to teicoplanin.MethodsA case‐series including all suspected anaphylactic reactions attributed to teicoplanin anaphylaxis within a single institution over a 29‐month period were categorised according to the probability of true IgE‐mediated anaphylaxis using previously published criteria. The number of patients who received teicoplanin was determined and used to calculate the rate of IgE‐mediated anaphylaxis.ResultsApproximately 18 800–19 600 patients received teicoplanin during the study period, during which there were 14 cases of suspected anaphylaxis attributed to the administration of teicoplanin: five were categorised as definite IgE‐mediated anaphylaxis, four as probable, two as uncertain and three were excluded. Of the excluded cases, two were found to have positive intradermal skin testing to alternative agents (rocuronium and chlorhexidine), and one did not meet the published clinical criteria.We therefore calculated the rate of IgE‐mediated anaphylaxis to be between 0.046% and 0.059% (equating to between 1:2088 and 1:1655).ConclusionsThis is the first study to calculate a rate of IgE‐mediated anaphylaxis to teicoplanin in clinical practice. Our case series suggests that these life‐threatening reactions occur less commonly than reported by the manufacturers. Mast cell tryptase is unreliable when used to predict the likelihood of IgE‐mediated anaphylaxis to teicoplanin.