A European-Japanese study on peach allergy: IgE to Pru p 7 associates with severity.

BACKGROUND: Pru p 3 and Pru p 7 have been implicated as risk factors for severe peach allergy. This study aimed to establish sensitization patterns to five peach components across Europe and in Japan, to explore their relation to pollen and foods and to predict symptom severity. METHODS: In twelve European (EuroPrevall project) and one Japanese outpatient clinic, a standardized clinical evaluation was conducted in 1231 patients who reported symptoms to peach and/or were sensitized to peach. Specific IgE against Pru p 1, 2, 3, 4 and 7 and against Cup s 7 was measured in 474 of them. Univariable and multivariable Lasso regression was applied to identify combinations of parameters predicting severity. RESULTS: Sensitization to Pru p 3 dominated in Southern Europe but was also quite common in Northern and Central Europe. Sensitization to Pru p 7 was low and variable in the European centers but very dominant in Japan. Severity could be predicted by a model combining age of onset of peach allergy, probable mugwort, Parietaria pollen and latex allergy, and sensitization to Japanese cedar pollen, Pru p 4 and Pru p 7 which resulted in an AUC of 0.73 (95% CI 0.73-0.74). Pru p 3 tended to be a risk factor in South Europe only. CONCLUSIONS: Pru p 7 was confirmed as a significant risk factor for severe peach allergy in Europe and Japan. Combining outcomes from clinical and demographic background with serology resulted in a model that could better predict severity than CRD alone.

First-time anterior cruciate ligament injury in adolescent female elite athletes: a prospective cohort study to identify modifiable risk factors.

PURPOSE: To identify modifiable biomechanical and neuromuscular anterior cruciate ligament (ACL) injury risk factors for first-time ACL injury in adolescent female elite football and team handball players. METHODS: Adolescent female elite football and handball players with no previous ACL injury participated in the present study. At baseline, players were tested during side-cutting manoeuvres performed in a 3-dimensional motion analysis laboratory with concomitant electromyography (EMG) measurements. Maximal isometric lower limb muscle strength was assessed by handheld dynamometry. Players were prospectively followed for 2 years after baseline testing, and all magnetic resonance imaging (MRI) verified ACL injuries were registered. The effect of 16 risk factor candidates on the relative risk (RR) of ACL injury was estimated using Poisson regression analysis. RESULTS: Ninety players (age 16.9 ± 1.2 years) were included in the analyses. Nine first-time ACL injuries (injury incidence 10.0% (95% confidence interval (CI) 5.4-18.6%)) were registered during the 2-year follow-up period. Four risk factor candidates were significantly associated with the risk of ACL injury: (1) hip flexion angle at initial contact (IC) [RR 0.56, 95% confidence interval (CI) 0.34-0.92], (2) internal knee rotation angle at IC [RR 1.13, 95% CI 1.08-1.19], (3) semitendinosus EMG activity 50 ms prior to IC [RR: 0.62, 95% CI 0.43-0.89], and (4) external hip rotator strength [RR: 0.77, 95% CI 0.66-0.89]. CONCLUSION: Four distinct ACL injury risk factors related to the side-cutting manoeuvre were identified in a population of adolescent female elite football and team handball players with no previous ACL injury. As ACL injury typically occur during side-cutting, intervention programmes to modify these risk factors pose a promising strategy for ACL injury prevention in adolescent female elite football and team handball. LEVEL OF EVIDENCE: II.

[Aconitine poisoning due to confusion of aconite leaves with lovage]. / Aconitinvergiftung durch eine Verwechslung von Eisenhutblättern mit Liebstöckel.

Due to a mix-up an older couple (69 years and 71 years) ate a meal with herbs from their garden that contained leaves of monkshood (Aconitum napellus). The monkshood plants grew close to the herbs in their garden. Both patients developed the typical symptoms of aconitine poisoning with paresthesia, hypotension and bradycardia. Over the course of time both developed cardiac arrhythmia with ventricular extrasystoles and required monitoring on the intensive care unit (ICU). The husband was more severely affected and needed catecholamines for successful treatment of hypotension (70/40 mmHg) and bradycardia (45 bpm). The toxicological analysis of the patients' serum taken 3.5 h after ingestion led to the detection of 1.8 ng/ml and 2.0 ng/ml aconitine, respectively. The patients were discharged in good general condition after 1 and 2 days, respectively. Monkshood (Aconitum napellus) is one of the most toxic native plants that can also be found in gardens due to its popularity as an ornamental plant. All parts of the plant contain toxic diterpenoid alkaloids, such as aconitine. Aconitine causes persistent activation of the fast voltage-gated sodium channels resulting in severe cardiac and neurological toxicity. Treatment of aconitine-induced ventricular arrhythmias is challenging as they are often refractory to electrical cardioversion and antiarrhythmic drugs.

Temporal variation of Staphylococcus aureus clonal complexes in atopic dermatitis: a follow-up study.

BACKGROUND: A strong link between disease severity and Staphylococcus aureus colonization of the skin has been reported in patients with atopic dermatitis (AD). OBJECTIVES: To examine temporal variations in S. aureus colonization and S. aureus CC type in patients with AD, and to investigate links to disease severity, skin barrier properties and filaggrin gene (FLG) mutations. METHODS: This was a follow-up study of a cohort of 101 adult patients with AD recruited from an outpatient clinic. Bacterial swabs were taken at baseline and follow-up from lesional skin, nonlesional skin and the nose. Swabs positive for S. aureus were characterized by spa and the respective clonal complex (CC) type was assigned. Patients were characterized with respect to disease severity [Scoring Atopic Dermatitis (SCORAD)], skin barrier properties [transepidermal water loss (TEWL), pH] and FLG mutations. RESULTS: In total, 63 patients participated in a follow-up visit. Twenty-seven patients (43%) were colonized at both visits, 27 were colonized at only one visit and nine (14%) were not colonized at either visit. Of patients colonized at both visits, 52% remained colonized with the same CC type at follow-up. Change in CC type was related to an increase in SCORAD of 10·7 points; patients who carried the same CC type had a reduction in SCORAD of 4·4 points. Significantly higher skin pH was found in patients colonized at both visits, while change in CC type was not related to TEWL, pH or FLG mutations. CONCLUSIONS: The data indicate that temporal variation in S. aureus CC type is linked to flares of the disease.

Fish oil in infancy protects against food allergy in Iceland-Results from a birth cohort study.

BACKGROUND: Consumption of oily fish or fish oil during pregnancy, lactation and infancy has been linked to a reduction in the development of allergic diseases in childhood. METHODS: In an observational study, Icelandic children (n = 1304) were prospectively followed from birth to 2.5 years with detailed questionnaires administered at birth and at 1 and 2 years of age, including questions about fish oil supplementation. Children with suspected food allergy were invited for physical examinations, allergic sensitization tests, and a double-blind, placebo-controlled food challenge if the allergy testing or clinical history indicated food allergy. The study investigated the development of sensitization to food and confirmed food allergy according to age and frequency of postnatal fish oil supplementation using proportional hazards modelling. RESULTS: The incidence of diagnosed food sensitization was significantly lower in children who received regular fish oil supplementation (relative risk: 0.51, 95% confidence interval: 0.32-0.82). The incidence of challenge-confirmed food allergy was also reduced, although not statistically significant (0.57, 0.30-1.12). Children who began to receive fish oil in their first half year of life were significantly more protected than those who began later (P = .045 for sensitization, P = .018 for allergy). Indicators of allergy severity decreased with increased fish oil consumption (P = .013). Adjusting for parent education and allergic family history did not change the results. CONCLUSION: Postnatal fish oil consumption is associated with decreased food sensitization and food allergies in infants and may provide an intervention strategy for allergy prevention.

Component-resolved diagnosis and beyond: Multivariable regression models to predict severity of hazelnut allergy.

BACKGROUND: Component-resolved diagnosis (CRD) has revealed significant associations between IgE against individual allergens and severity of hazelnut allergy. Less attention has been given to combining them with clinical factors in predicting severity. AIM: To analyze associations between severity and sensitization patterns, patient characteristics and clinical history, and to develop models to improve predictive accuracy. METHODS: Patients reporting hazelnut allergy (n = 423) from 12 European cities were tested for IgE against individual hazelnut allergens. Symptoms (reported and during Double-blind placebo-controlled food challenge [DBPCFC]) were categorized in mild, moderate, and severe. Multiple regression models to predict severity were generated from clinical factors and sensitization patterns (CRD- and extract-based). Odds ratios (ORs) and areas under receiver-operating characteristic (ROC) curves (AUCs) were used to evaluate their predictive value. RESULTS: Cor a 9 and 14 were positively (OR 10.5 and 10.1, respectively), and Cor a 1 negatively (OR 0.14) associated with severe symptoms during DBPCFC, with AUCs of 0.70-073. Combining Cor a 1 and 9 improved this to 0.76. A model using a combination of atopic dermatitis (risk), pollen allergy (protection), IgE against Cor a 14 (risk) and walnut (risk) increased the AUC to 0.91. At 92% sensitivity, the specificity was 76.3%, and the positive and negative predictive values 62.2% and 95.7%, respectively. For reported symptoms, associations and generated models proved to be almost identical but weaker. CONCLUSION: A model combining CRD with clinical background and extract-based serology is superior to CRD alone in assessing the risk of severe reactions to hazelnut, particular in ruling out severe reactions.

[Trends in Abuse of Biogenic Drugs in Parts of Germany 2007-2013]. / Entwicklung des Missbrauchs psychotroper Pflanzen und Pilze in Deutschland ­ Interpretation der Zahlen aus 3 Giftinformationszentren für die Jahre 2007­2013.

AIM OF THE STUDY: Based on an abundance of information on the internet, psychotropic plants and mushrooms are of increasing relevance as legal and cheap alternatives to other illicit drugs. Due to the lack of a German database, the abuse of selected biogenic drugs using reported exposures to 3 German Poison Information Centres (PICs) was examined. METHODS: Information on abuse of biogenic drugs was collected from the German PICs in Berlin, Erfurt and Fribourg (2007-2013). RESULTS: 602 drug abuses were reported to the selected PICs. 52% reported consumption of tropane alkaloid-containing plants (Angel's trumpet, Thorn apple, Belladonna), 25% of psilocybin-containing mushrooms and 10% of nutmeg. Angel's trumpet was identified as the most abused plant. Consumers of tropane alkaloid-containing plants were mainly adolescents, whereas the majority of the abusers of psilocybin-containing mushrooms and nutmeg were rather young grown-ups and school children, respectively. A preponderance of moderate and severe effects (55%) could be noticed for exposures to tropane alkaloid-containing plants. More than 90% of suspected cases of tropane alkaloid-containing as well as psilocybin-containing plants abuse resulted in the treatment recommendation 'surveillance in hospital'. Mydriasis, hallucinations, tachycardia and agitation were the main symptoms after the abuse of biogenic drugs. CONCLUSIONS: The data from the PICs suggest abuse of biogenic drugs in parts of Germany. A decreasing trend is observed, probably caused by the competition with new synthetic designer drugs. The results underline the dominance of Angel's trumpet in the abuse of biogenic drugs and emphasize the importance of easy accessibility for the abuse of biogenic drugs. Unexpectedly, the number of nutmeg abuse cases increased during the investigated period.

Staphylococcus aureus colonization in atopic eczema and its association with filaggrin gene mutations.

BACKGROUND: Atopic dermatitis (AD) is a prevalent disease with significant impact on physical health and quality of life. Staphylococcus aureus has been directly correlated to disease severity, and may also be a contributing causal factor in the pathogenesis of AD. OBJECTIVES: The primary aim was to assess differences in S. aureus colonization in patients with AD with and without filaggrin gene mutations. The secondary aim was to assess disease severity in relation to S. aureus colonization. Exploratory analyses were performed to investigate S. aureus genetic lineages in relation to filaggrin gene (FLG) mutations and disease severity. METHODS: Adult patients with AD (n = 101) were included in the study. Bacterial swabs were taken from lesional skin, nonlesional skin and the nose. Swabs positive for S. aureus were characterized by spa and the respective clonal complex (CC) type assigned. Patients were characterized with respect to disease severity (Scoring Atopic Dermatitis) and FLG mutations (n = 88). Fisher's exact test was used to analyse differences in S. aureus colonization in relation to FLG mutations. RESULTS: Of the 101 patients included, 74 (73%) were colonized with S. aureus. Of the colonized patients, 70 (95%) carried only one CC type in all three different sampling sites. In lesional skin, S. aureus was found in 24 of 31 patients with FLG mutations vs. 24 of 54 wild-type patients (P = 0·0004). Staphylococcus aureusCC1 clonal lineage was more prevalent in patients with FLG mutations (n = 10) than in wild-type patients (n = 2) (P = 0·003). No specific bacterial lineage was linked to disease severity. CONCLUSIONS: Increased S. aureus colonization in patients with AD with FLG mutations, and increased prevalence of CC1 in patients with FLG mutations, suggest that host-microbe interactions and clonal differences in S. aureus are important for colonization of AD skin.

Dissecting the actin cortex density and membrane-cortex distance in living cells by super-resolution microscopy.

Nanoscale spacing between the plasma membrane and the underlying cortical actin cytoskeleton profoundly modulates cellular morphology, mechanics, and function. Measuring this distance has been a key challenge in cell biology. Current methods for dissecting the nanoscale spacing either limit themselves to complex survey design using fixed samples or rely on diffraction-limited fluorescence imaging whose spatial resolution is insufficient to quantify distances on the nanoscale. Using dual-color super-resolution STED (stimulated-emission-depletion) microscopy, we here overcome this challenge and accurately measure the density distribution of the cortical actin cytoskeleton and the distance between the actin cortex and the membrane in live Jurkat T-cells. We found an asymmetric cortical actin density distribution with a mean width of 230 (+105/-125) nm. The spatial distances measured between the maximum density peaks of the cortex and the membrane were bi-modally distributed with mean values of 50 ± 15 nm and 120 ± 40 nm, respectively. Taken together with the finite width of the cortex, our results suggest that in some regions the cortical actin is closer than 10 nm to the membrane and a maximum of 20 nm in others.

Glenohumeral and scapulothoracic strength impairments exists in patients with subacromial impingement, but these are not reflected in the shoulder pain and disability index.

BACKGROUND: Pain and loss of function are cardinal symptoms associated with Subacromial impingement syndrome (SIS), while the presence and magnitude of deficits in strength and range of motion (ROM) are largely undescribed in non-athletic patients with SIS. Moreover, the relevance of impairments in strength and ROM to patient-reported shoulder function is not well described, even though testing of strength is recommended in clinical guidelines. The purpose of this study was, first, to investigate impairments in glenohumeral and scapulothoracic strength and in abduction and internal rotation ROM in patients with SIS. Secondly, to investigate the influence of these impairments on patient-reported shoulder function. METHODS: Cross-sectional study based on a consecutive cohort of 157 patients referred to specialist examination and diagnosed with shoulder impingement (SIS) using predefined validated diagnostic criteria. Prior to specialist examination, questionnaires regarding shoulder function (Shoulder Pain And Disability Index, SPADI) demographics and kinesiophobia (TSK-11) were collected, and shoulder strength and ROM was measured by trained testers, with the patient reporting pain levels during testing and for the last week. Impairments in strength (abduction, external-rotation, (protraction and horizontal-extension) and ROM (abduction and internal rotation) were investigated in patients with unilateral shoulder pain, using one-sample t-tests. SPADI total score (SPADI) and SPADI function score (SPADI-F), were chosen as dependent variables in multiple regressions to investigate the influence of impairments on patient-reported shoulder function. Independent variables of interest were; strength in abduction and external rotation, abduction ROM, pain-during-tests, pain-last-week and kinesiophobia. RESULTS: Significant impairments were found for all impairment tests, but most pronounced for glenohumeral strength and abduction ROM (29-33% deficits), and less for scapulothoracic strength and internal rotation ROM (8-18% deficits). Pain variables influenced SPADI and SPADI-F score to a high degree (R2 = 23.4-31.6%, p < 0.001), while strength and ROM did not. CONCLUSION: Substantial strength and ROM impairments were found in patients with SIS. Only pain significantly influenced patient-reported function, while impairments did not. As SPADI score does not reflect the substantial strength and ROM impairments in external rotation and abduction observed in patients with SIS, supplemental assessment of these impairments seems important.

Incidence and natural history of hen's egg allergy in the first 2 years of life-the EuroPrevall birth cohort study.

BACKGROUND: Parents and health staff perceive hen's egg allergy (HEA) as a common food allergy in early childhood, but the true incidence is unclear because population-based studies with gold-standard diagnostic criteria are lacking. OBJECTIVE: To establish the incidence and course of challenge-confirmed HEA in children, from birth until the age of 24 months, in different European regions. METHODS: In the EuroPrevall birth cohort study, children with a suspected HEA and their age-matched controls were evaluated in 9 countries, using a standardized protocol including measurement of HE-specific immunoglobulin E-antibodies in serum, skin prick tests, and double-blind, placebo-controlled food challenges (DBPCFC). RESULTS: Across Europe, 12 049 newborns were enrolled, and 9336 (77.5%) were followed up to 2 years of age. In 298 children, HEA was suspected and DBPCFC was offered. HEA by age two was confirmed in 86 of 172 challenged children (mean raw incidence 0.84%, 95% confidence interval (95% CI) 0.67-1.03). Adjusted mean incidence of HEA was 1.23% (95% CI 0.98-1.51) considering possible cases among eligible children who were not challenged. Centre-specific incidence ranged from United Kingdom (2.18%, 95% CI 1.27-3.47) to Greece (0.07%). Half of the HE-allergic children became tolerant to HE within 1 year after the initial diagnosis. CONCLUSIONS: The largest multinational European birth cohort study on food allergy with gold-standard diagnostic methods showed that the mean adjusted incidence of HEA was considerably lower than previously documented, although differences in incidence rates among countries were noted. Half of the children with documented HEA gained tolerance within 1 year postdiagnosis.

Synthesis of sp(3)-rich scaffolds for molecular libraries through complexity-generating cascade reactions.

An efficient strategy for the synthesis of complex small molecules from simple building blocks is presented. Key steps of the strategy include tandem Petasis and Diels-Alder reactions, and divergent complexity-generating cyclization cascades from a key dialdehyde intermediate. The methodology is validated through the synthesis of a representative compound set, which has been used in the production of 1617 molecules for the European Lead Factory.

Self-reported previous knee injury and low knee function increase knee injury risk in adolescent female football.

Knee injuries are common in adolescent female football. Self-reported previous knee injury and low Knee injury and Osteoarthritis Outcome Score (KOOS) are proposed to predict future knee injuries, but evidence regarding this in adolescent female football is scarce. The aim of this study was to investigate self-reported previous knee injury and low KOOS subscale score as risk factors for future knee injuries in adolescent female football. A sample of 326 adolescent female football players, aged 15-18, without knee injury at baseline, were included. Data on self-reported previous knee injury and KOOS questionnaires were collected at baseline. Time-loss knee injuries and football exposures were reported weekly by answers to standardized text-message questions, followed by injury telephone interviews. A priori, self-reported previous knee injury and low KOOS subscale scores (< 80 points) were chosen as independent variables in the risk factor analyses. The study showed that self-reported previous knee injury significantly increased the risk of time-loss knee injury [relative risk (RR): 3.65, 95% confidence (CI) 1.73-7.68; P < 0.001]. Risk of time-loss knee injury was also significantly increased in players with low KOOS subscale scores (< 80 points) in Activities of Daily Living (RR: 5.0), Sport/Recreational (RR: 2.2) and Quality of Life (RR: 3.0) (P < 0.05). In conclusion, self-reported previous knee injury and low scores in three KOOS subscales significantly increase the risk of future time-loss knee injury in adolescent female football.

Quality of life and disease severity in patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) affects quality of life (QoL) negatively in patients and their families. We examined the relationship between disease severity and QoL in patients with AD. METHODS: Consecutive, newly referred outpatients with AD, 4 years of age or older, were assessed from January 2012 onwards by means of the dermatology life quality index (DLQI, range 0-30), the Scoring of AD (SCORAD) disease severity score (range 0-103), filaggrin gene (FLG) mutation status and paraclinical tests related to allergy. RESULTS: A total of 250 patients with a mean age of 26.0 years were identified with complete data on DLQI; 148 (59.2%) females and 102 (40.8%) males. Of these 45.6% had asthma, 46.8% had hay fever, 22.7% had a loss-of-function mutation in FLG, and 61.9% had one or more inhalant allergic sensitizations. The correlation between SCORAD and DLQI was 0.42 (P < 0.001). After multivariate adjustment there was an increasing mean DLQI score with increasing disease severity measured by SCORAD (DLQI in mild = 5.30, moderate = 8.59 and severe = 11.94 AD), P-value for difference between groups <0.001; a higher mean DLQI among females than males (9.73 vs. 8.34), P = 0.028; and among patients reporting facial eczema (9.88 vs. 6.24), P = 0.012. No statistically significant influence on DLQI was found for hand or foot eczema, age, blood eosinophil count, allergic sensitization, asthma, hay fever, FLG mutation status and smoking. FLG null mutation status was not significantly associated with SCORAD. CONCLUSION: AD impacts negatively on the QoL, proportional to the severity of the disease. Furthermore, female sex and facial eczema are associated with low QoL. Positive FLG null mutation status is not associated with QoL or disease severity.

Incidence and natural history of challenge-proven cow's milk allergy in European children--EuroPrevall birth cohort.

BACKGROUND: Cow's milk allergy (CMA) is one of the most commonly reported childhood food problems. Community-based incidence and prevalence estimates vary widely, due to possible misinterpretations of presumed reactions to milk and differences in study design, particularly diagnostic criteria. METHODS: Children from the EuroPrevall birth cohort in 9 European countries with symptoms possibly related to CMA were invited for clinical evaluation including cows' milk-specific IgE antibodies (IgE), skin prick test (SPT) reactivity and double-blind, placebo-controlled food challenge. RESULTS: Across Europe, 12 049 children were enrolled, and 9336 (77.5%) were followed up to 2 years of age. CMA was suspected in 358 children and confirmed in 55 resulting in an overall incidence of challenge-proven CMA of 0.54% (95% CI 0.41-0.70). National incidences ranged from 1% (in the Netherlands and UK) to <0.3% (in Lithuania, Germany and Greece). Of all children with CMA, 23.6% had no cow's milk-specific IgE in serum, especially those from UK, the Netherlands, Poland and Italy. Of children with CMA who were re-evaluated one year after diagnosis, 69% (22/32) tolerated cow's milk, including all children with non-IgE-associated CMA and 57% of those children with IgE-associated CMA. CONCLUSIONS: This unique pan-European birth cohort study using the gold standard diagnostic procedure for food allergies confirmed challenge-proven CMA in <1% of children up to age 2. Affected infants without detectable specific antibodies to cow's milk were very likely to tolerate cow's milk one year after diagnosis, whereas only half of those with specific antibodies in serum 'outgrew' their disease so soon.

IgE recognition patterns in peanut allergy are age dependent: perspectives of the EuroPrevall study.

BACKGROUND: We tested the hypothesis that specific molecular sensitization patterns correlate with the clinical data/manifestation in a European peanut-allergic population characterized under a common protocol. METHODS: Sixty-eight peanut-allergic subjects and 82 tolerant controls from 11 European countries were included. Allergy to peanut and lowest symptom-eliciting dose was established by double-blind placebo-controlled food challenge in all but anaphylactic subjects. Information of early or late (before or after 14 years of age) onset of peanut allergy was obtained from standardized questionnaires. IgE to peanut allergens rAra h 1-3, 6, 8-9, profilin and CCD was determined using ImmunoCAP. RESULTS: Seventy-eight percent of peanut allergics were sensitized to peanut extract and 90% to at least one peanut component. rAra h 2 was the sole major allergen for the peanut-allergic population. Geographical differences were observed for rAra h 8 and rAra h 9, which were major allergens for central/western and southern Europeans, respectively. Sensitization to rAra h 1 and 2 was exclusively observed in early-onset peanut allergy. Peanut-tolerant subjects were frequently sensitized to rAra h 8 or 9 but not to storage proteins. Sensitization to Ara h 2 ≥ 1.0 kUA /l conferred a 97% probability for a systemic reaction (P = 0.0002). Logistic regression revealed a significant influence of peanut extract sensitization and region on the occurrence of systemic reactions (P = 0.0185 and P = 0.0436, respectively). CONCLUSION: Sensitization to Ara h 1, 2 and 3 is usually acquired in childhood. IgE to Ara h 2 ≥ 1.0 kUA /l is significantly associated with the development of systemic reactions to peanut.

Predictors of health-related quality of life of European food-allergic patients.

BACKGROUND: Although food allergy has universally been found to impair HRQL, studies have found significant differences in HRQL between countries, even when corrected for differences in perceived disease severity. However, little is known about factors other than disease severity which may contribute to HRQL in food-allergic patients. Therefore, the aim of this study was to identify factors which may predict HRQL of food-allergic patients and also to investigate the specific impact of having experienced anaphylaxis and being prescribed an EAI on HRQL. METHODS: A total of 648 European food-allergic patients (404 adults, 244 children) completed an age-specific questionnaire package including descriptive questions. Multivariable regression analyses were performed to develop models for predicting HRQL of these patients. RESULTS: For adults, the prediction model accounted for 62% of the variance in HRQL and included perceived disease severity, type of symptoms, having a fish or milk allergy, and gender. For children, the prediction model accounted for 28% of the variance in HRQL and included perceived disease severity, having a peanut or soy allergy, and country of origin. For both adults and children, neither experiencing anaphylaxis nor being prescribed an epinephrine auto-injector (EAI) contributed to impairment of HRQL. CONCLUSIONS: In this study, food allergy-related HRQL may be predicted to a greater extent in adults than in children. Allergy to certain foods may cause greater HRQL impairment than others. Country of origin may affect HRQL, at least in children. Experiencing anaphylaxis or being prescribed an EAI has no impact on HRQL in either adults or children.

The EuroPrevall outpatient clinic study on food allergy: background and methodology.

BACKGROUND: The EuroPrevall project aimed to develop effective management strategies in food allergy through a suite of interconnected studies and a multidisciplinary integrated approach. To address some of the gaps in food allergy diagnosis, allergen risk management and socio-economic impact and to complement the EuroPrevall population-based surveys, a cross-sectional study in 12 outpatient clinics across Europe was conducted. We describe the study protocol. METHODS: Patients referred for immediate food adverse reactions underwent a consistent and standardized allergy work-up that comprised collection of medical history; assessment of sensitization to 24 foods, 14 inhalant allergens and 55 allergenic molecules; and confirmation of clinical reactivity and food thresholds by standardized double-blind placebo-controlled food challenges (DBPCFCs) to milk, egg, fish, shrimp, peanut, hazelnut, celeriac, apple and peach. RESULTS: A standardized methodology for a comprehensive evaluation of food allergy was developed and implemented in 12 outpatient clinics across Europe. A total of 2121 patients (22.6% <14 years) reporting 8257 reactions to foods were studied, and 516 DBPCFCs were performed. CONCLUSIONS: This is the largest multicentre European case series in food allergy, in which subjects underwent a comprehensive, uniform and standardized evaluation including DBPCFC, by a methodology which is made available for further studies in food allergy. The analysis of this population will provide information on the different phenotypes of food allergy across Europe, will allow to validate novel in vitro diagnostic tests, to establish threshold values for major allergenic foods and to analyse the socio-economic impact of food allergy.

A hydrogel based nanosensor with an unprecedented broad sensitivity range for pH measurements in cellular compartments.

Optical pH nanosensors have been applied for monitoring intracellular pH in real-time for about two decades. However, the pH sensitivity range of most nanosensors is too narrow, and measurements that are on the borderline of this range may not be correct. Furthermore, ratiometric measurements of acidic intracellular pH (pH < 4) in living cells are still challenging due to the lack of suitable nanosensors. In this paper we successfully developed a multiple sensor, a fluorophore based nanosensor, with an unprecedented broad measurement range from pH 1.4 to 7.0. In this nanosensor, three pH-sensitive fluorophores (difluoro-Oregon Green, Oregon Green 488, and fluorescein) and one pH-insensitive fluorophore (Alexa 568) were covalently incorporated into a nanoparticle hydrogel matrix. With this broad range quadruple-labelled nanosensor all physiological relevant pH levels in living cells can be measured without being too close to the limits of its pH-range. The nanosensor exhibits no susceptibility to interference by other intracellular ions at physiological concentrations. Due to its positive surface charge it is spontaneously internalized by HeLa cells and localizes to the lysosomes where the mean pH was measured at 4.6. This quadruple-labelled nanosensor performs accurate measurements of fluctuations of lysosomal pH in both directions, which was shown by treatment with the V-ATPase inhibitor bafilomycin A1 or its substrate ATP in HeLa cells. These measurements indicate that this novel quadruple-labelled nanosensor is a promising new tool for measuring the pH of acidic compartments in living cells.