A major proportion of allergic reactions to hazelnuts (Corylus avellana) are caused by immunologic cross-reactivity of IgE antibodies to pathogenesis-related class 10 (PR-10) proteins. Intriguingly, ...the four known isoforms of the hazelnut PR-10 allergen Cor a 1, denoted as Cor a 1.0401-Cor a 1.0404, share sequence identities exceeding 97% but possess different immunologic properties. In this work we describe the NMR solution structures of these proteins and provide an in-depth study of their biophysical properties. Despite sharing highly similar three-dimensional structures, the four isoforms exhibit remarkable differences regarding structural flexibility, hydrogen bonding and thermal stability. Our experimental data reveal an inverse relation between structural flexibility and IgE-binding in ELISA experiments, with the most flexible isoform having the lowest IgE-binding potential, while the isoform with the most rigid backbone scaffold displays the highest immunologic reactivity. These results point towards a significant entropic contribution to the process of antibody binding.
Background Severe anaphylaxis to honeybee or vespid stings is associated with a variety of risk factors, which are poorly defined. Objective Our aim was to evaluate the association of baseline serum ...tryptase concentrations and other variables routinely recorded during patient evaluation with the frequency of past severe anaphylaxis after a field sting. Methods In this observational multicenter study, we enrolled 962 patients with established bee or vespid venom allergy who had a systemic reaction after a field sting. Data were collected on tryptase concentration, age, sex, culprit insect, cardiovascular medication, and the number of preceding minor systemic reactions before the index field sting. A severe reaction was defined as anaphylactic shock, loss of consciousness, or cardiopulmonary arrest. The index sting was defined as the hitherto first, most severe systemic field-sting reaction. Relative rates were calculated with generalized additive models. Results Two hundred six (21.4%) patients had a severe anaphylactic reaction after a field sting. The frequency of this event increased significantly with higher tryptase concentrations (nonlinear association). Other factors significantly associated with severe reactions after a field sting were vespid venom allergy, older age, male sex, angiotensin-converting enzyme inhibitor medication, and 1 or more preceding field stings with a less severe systemic reaction. Conclusion In patients with honeybee or vespid venom allergy, baseline serum tryptase concentrations are associated with the risk for severe anaphylactic reactions. Preventive measures should include substitution of angiotensin-converting enzyme inhibitors.
Decompression sickness and arterial gas embolism, collectively known as decompression illness (DCI), are serious medical conditions that can result from compressed gas diving. DCI can present with a ...wide range of physiologic and neurologic symptoms. In diving medicine, skin manifestations are usually described in general as cutis marmorata (CM). Mainly in the Anglo-American literature the terms cutis marmorata, livedo reticularis (LR), and livedo racemosa (LRC) are used interchangeably but actually describe pathophysiologically different phenomena. CM is a synonym for LR, which is a physiological and benign, livid circular discoloration with a net-like, symmetric, reversible, and uniform pattern. The decompression-associated skin discolorations, however, correspond to the pathological, irregular, broken netlike pattern of LRC. Unlike in diving medicine, in clinical medicine/dermatology the pathology of livedo racemosa is well described as a thrombotic/embolic occlusion of arteries. This concept of arterial occlusion suggests that the decompression-associated livedo racemosa may be also caused by arterial gas embolism. Recent studies have shown a high correlation of cardiac right/left (R/L) shunts with arterial gas embolism and skin bends in divers with unexplained DCI. To further investigate this hypothesis, a retrospective analysis was undertaken in a population of Austrian, Swiss, and German divers. The R/L shunt screening results of 18 divers who suffered from an unexplained decompression illness (DCI) and presented with livedo racemosa were retrospectively analyzed. All of the divers were diagnosed with a R/L shunt, 83% with a cardiac shunt patent foramen ovale (PFO)/atrium septum defect (ASD), and 17% with a non-cardiac shunt. We therefore not only confirm this hypothesis but when using appropriate echocardiographic techniques even found a 100% match between skin lesions and R/L shunt. In conclusion, in diving medicine the term cutis marmorata/livedo reticularis is used incorrectly for describing the actual pathology of livedo racemosa. Moreover, this pathology could be a good explanation for the high correlation of livedo racemosa with cardiac and non-cardiac right/left shunts in divers without omission of decompression procedures.
Device-to-device (D2D) communications underlaying a cellular infrastructure has recently been proposed as a means of increasing the resource utilization, improving the user throughput and extending ...the battery lifetime of user equipments. In this article we propose a new distributed power control algorithm that iteratively determines the signal-to-noise-and-interference-ratio (SINR) targets in a mixed cellular and D2D environment and allocates transmit powers such that the overall power consumption is minimized subject to a sum-rate constraint. The performance of the distributed power control algorithm is benchmarked with respect to the optimal SINR target setting that we obtain using the Augmented Lagrangian Penalty Function method. The proposed scheme shows consistently near optimum performance both in a single-input-multiple-output and a multiple-input-multiple-output setting. We also propose a joint power control and mode selection algorithm that requires single cell information only and clearly outperforms the classical cellular mode operation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background Severe side effects during venom immunotherapy (VIT) are associated with a variety of risk factors. Objective Our aim was to evaluate the association of baseline serum tryptase ...concentration (BTC) and of other parameters, which are routinely recorded during patient evaluation, with the frequency of severe reactions requiring an emergency intervention during the buildup phase of VIT. Methods In this observational prospective multicenter study, we enrolled 680 patients with established honeybee or vespid venom allergy who underwent VIT. Data were collected on tryptase concentration, age, sex, culprit insect, cardiovascular medication, degree of preceding sting reaction, preventive antiallergic medication before therapy, time between last preceding sting reaction and VIT, venom specific IgE concentration, and type of buildup procedure. Relative rates were calculated with generalized additive models. Results Fifty-seven patients (8.4%) required an emergency intervention during buildup because of a severe systemic reaction. The frequency of interventions increased significantly with higher BTC (log-linear association; adjusted odds ratio, 1.56; 95% CI, 1.15-2.11; P < .005). The predictive power of BTC was markedly greater when VIT was performed for vespid venom allergy than for bee venom (for bee VIT, no significant association; for vespid VIT, log-linear association; adjusted odds ratio, 2.33; 95% CI, 1.28-4.26; P = .005). The most important other factor significantly associated with severe reactions during the buildup phase of VIT was bee venom allergy. Conclusion Before vespid VIT, measurement of baseline serum tryptase concentration should be used to identify patients with a high risk for side effects. Patients with bee venom allergy require a particularly high degree of surveillance during VIT.
The rare, but emerging mold Aspergillus terreus is an important pathogen in some geographical areas, like Tyrol (Austria) and Houston (Texas). The reason for this high prevalence is unknown. The ...present serosurveillance study aimed to evaluate the trends in levels of A. terreus-specific IgG antibodies in various regions of Tyrol and to compare the results to the environmental spread of A. terreus in Tyrol. Therefore, 1058 serum samples from healthy blood donors were evaluated. Data revealed a significant difference between the Tyrolean Upland and Lowland. Moreover, female participants had higher A. terreus IgG antibody levels than male participants. The differences found in our study are consistent with the distributional differences in environmental and clinical samples described in previous studies, supporting that A. terreus IgG antibody levels reflect the environmental epidemiology of A. terreus in Tyrol.
Dupilumab is the first biological treatment approved for moderate-to-severe atopic dermatitis (AD). Efficacy and safety have been demonstrated in clinical trials, but real-life data is still limited. ...The objective of this study was to retrospectively evaluate Dupilumab treatment in AD patients in a real-life clinical setting. Effectiveness and safety outcomes were collected at baseline and after 2, 6, 10, 24, 39, and 52 weeks by using clinical scores for disease activity, as well as serological markers. Ninety-four patients from five dermatological hospitals were included. After 24 weeks of treatment, the median Investigator Global Assessment (IGA) and Eczema Area and Severity Index (EASI) showed a significant reduction compared to baseline (3.9 ± 0.7 vs. 1.4 ± 0.8 and 26.5 ± 12.5 vs. 6.4 ± 6.5). Interestingly, we observed rosacea-like folliculitis as an unexpected side effect in 6.4% of patients. Dupilumab proves to be an effective and well-tolerated treatment under real-life conditions. The occurrence of rosacea-like folliculitis warrants further mechanistic investigation.
Intercell interference coordination (ICIC) in or-thogonal frequency division multiple access (OFDMA) net¬works in general and in the 3GPP Long Term Evolution system in particular has received much ...attention both from the academia and the standardization communities. Under¬standing the trade-offs associated with ICIC mechanisms is important, because it helps identify the architecture and protocol support that allows practical systems to realize potential performance gains. In this paper we review some of the recent advances in ICIC research and discuss the assumptions, advantages and limitations of some of the proposed mechanisms. We then proceed to describe the architecture and protocol support for ICIC in the 3GPP LTE system. We make the point that the 3GPP standard is formed in a flexible way such that network operators can employ the most suitable ICIC mechanism tailored to their actual deployment scenario, traffic situation and preferred performance target.
Summary Background Lyme borreliosis develops in 1–5% of individuals bitten by ticks, but with a diagnostic gap affecting up to 30% of patients, a broadly applicable pharmacological prevention ...strategy is needed. Topical azithromycin effectively eradicated Borrelia burgdorferi sensu lato from the skin in preclinical studies. We assessed its efficacy in human beings. Methods In this randomised, double-blind, placebo-controlled, multicentre trial done in 28 study sites in Germany and Austria, adults were equally assigned to receive topical 10% azithromycin or placebo twice daily for 3 consecutive days, within 72 h of a tick bite being confirmed. Randomisation numbers, which were stratified by study site, were accessed in study centres via an interactive voice-response system, by pharmacists not involved in the study. The primary outcome was the number of treatment failures, defined as erythema migrans, seroconversion, or both, in participants who were seronegative at baseline, had no further tick bites during the study, and had serology results available at 8 weeks (intention-to-treat ITT population). This study is registered with EudraCT, number 2011-000117-39. Findings Between July 7, 2011, and Dec 3, 2012, 1371 participants were randomly assigned to treatment, of whom 995 were included in the ITT population. The trial was stopped early because an improvement in the primary endpoint in the group receiving azithromycin was not reached. At 8 weeks, 11 (2%) of 505 in the azithromycin group and 11 (2%) of 490 in the placebo group had treatment failure (odds ratio 0·97, 95% CI 0·42–2·26, p=0·47). Topical azithromycin was well tolerated. Similar numbers of patients had adverse events in the two groups (175 26% of 505 vs 177 26% of 490, p=0·87), and most adverse events were mild. Interpretation Topical azithromycin was well tolerated and had a good safety profile. Inclusion of asymptomatic seroconversion into the primary efficacy analysis led to no prevention effect with topical azithromycin. Adequately powered studies assessing only erythema migrans should be considered. A subgroup analysis in this study suggested that topical azithromycin reduces erythema migrans after bites of infected ticks. Funding Ixodes AG.
Treatment failure during venom immunotherapy (VIT) may be associated with a variety of risk factors.
Our aim was to evaluate the association of baseline serum tryptase concentration (BTC) and of ...other parameters with the frequency of VIT failure during the maintenance phase.
In this observational prospective multicenter study, we followed 357 patients with established honey bee or vespid venom allergy after the maintenance dose of VIT had been reached. In all patients, VIT effectiveness was either verified by sting challenge (n = 154) or patient self-reporting of the outcome of a field sting (n = 203). Data were collected on BTC, age, gender, preventive use of anti-allergic drugs (oral antihistamines and/or corticosteroids) right after a field sting, venom dose, antihypertensive medication, type of venom, side effects during VIT, severity of index sting reaction preceding VIT, and duration of VIT. Relative rates were calculated with generalized additive models.
22 patients (6.2%) developed generalized symptoms during sting challenge or after a field sting. A strong association between the frequency of VIT failure and BTC could be excluded. Due to wide confidence bands, however, weaker effects (odds ratios <3) of BTC were still possible, and were also suggested by a selective analysis of patients who had a sting challenge. The most important factor associated with VIT failure was a honey bee venom allergy. Preventive use of anti-allergic drugs may be associated with a higher protection rate.
It is unlikely that an elevated BTC has a strong negative effect on the rate of treatment failures. The magnitude of the latter, however, may depend on the method of effectiveness assessment. Failure rate is higher in patients suffering from bee venom allergy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
