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Walnut Allergy Across Europe: Distribution of Allergen Sensitization Patterns and Prediction of Severity.Background: Walnut allergy is common across the globe, but data on the involvement of individual walnut components are scarce. Objectives: To identify geographical differences in walnut component sensitization across Europe, explore cosensitization and cross-reactivity, and assess associations of clinical and serological determinants with severity of walnut allergy. Methods: As part of the EuroPrevall outpatient surveys in 12 European cities, standardized clinical evaluation was conducted in 531 individuals reporting symptoms to walnut, with sensitization to all known walnut components assessed in 202 subjects. Multivariable Lasso regression was applied to investigate predictors for walnut allergy severity. Results: Birch-pollen-related walnut sensitization (Jug r 5) dominated in Northern and Central Europe and lipid transfer protein sensitization (Jug r 3) in Southern Europe. Profilin sensitization (Jug r 7) was prominent throughout Europe. Sensitization to storage proteins (Jug r 1, 2, 4, and 6) was detected in up to 10% of subjects. The walnut components that showed strong correlations with pollen and other foods differed between centers. The combination of determinants best predicting walnut allergy severity were symptoms upon skin contact with walnut, atopic dermatitis (ever), family history of atopic disease, mugwort pollen allergy, sensitization to cat or dog, positive skin prick test result to walnut, and IgE to Jug r 1, 5, 7, or carbohydrate determinants (area under the curve = 0.81; 95% CI, 0.73-0.89). Conclusions: Walnut-allergic subjects across Europe show clear geographical differences in walnut component sensitization and cosensitization patterns. A predictive model combining results from component-based serology testing with results from extract-based testing and information on clinical background allows for good discrimination between mild to moderate and severe walnut allergy. Keywords: Allergen components; EuroPrevall; Europe; IgE sensitization; Prediction; Severity; Walnut allergy; iFAAM.
Regular Physical Activity Levels and Incidence of Restrictive Spirometry Pattern: A Longitudinal Analysis of 2 Population-Based Cohorts.We estimated the association between regular physical activity and the incidence of restrictive spirometry pattern. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and physical activity were assessed in 2 population-based European cohorts (European Community Respiratory Health Survey: n = 2,757, aged 39-67 years; and Swiss Study on Air Pollution and Lung and Heart Diseases in Adults: n = 2,610, aged 36-82 years) first in 2000-2002 and again approximately 10 years later (2010-2013). Subjects with restrictive or obstructive spirometry pattern at baseline were excluded. We assessed the association of being active at baseline (defined as being physically active at least 2-3 times/week for ≥1 hour) with restrictive spirometry pattern at follow-up (defined as a postbronchodilation FEV1/FVC ratio of at least the lower limit of normal and FVC of <80% predicted) using modified Poisson regression, adjusting for relevant confounders. After 10 years of follow-up, 3.3% of participants had developed restrictive spirometry pattern. Being physically active was associated with a lower risk of developing this phenotype (relative risk = 0.76, 95% confidence interval: 0.59, 0.98). This association was stronger among those who were overweight and obese than among those of normal weight (P for interaction = 0.06). In 2 large European studies, adults practicing regular physical activity were at lower risk of developing restrictive spirometry pattern over 10 years. Keywords: BMI; FVC; physical activity; restrictive spirometry; spirometry.
Suicide rates in Iceland before and after the 2008 Global Recession: a nationwide population-based study.Background: Economic downturns have been associated with increased suicide rates. The 2008 global financial crisis varied across countries but hit Iceland relatively hard. We aimed to study potential changes in suicide rates in Iceland during this major economic transition. Methods: Data were retrieved on all suicides in Iceland during 2002-14. The study period was divided into a pre-collapse period (2002-08) and a post-collapse period (2008-14). Poisson regression models were used to estimate the association between pre-to-post economic collapse and suicide rates, expressed as risk ratios (RR) with 95% confidence intervals (CIs). Analyses were stratified by age and sex. Results: A total of 470 suicides were recorded during the study period. The mean age at death was 45 years and 75% were males. The overall suicide rates per 100 000 were 13.3 pre-collapse and 15 post-collapse revealing no overall differences in pre-to-post collapse (RR 1.12; CI 0.94-1.35). This was true for both men and women (RR 1.18; CI 0.96-1.46 and RR 0.96; CI 0.67-1.38, respectively). An increase in the unemployment rate was not associated with the overall suicide rate (RR 1.07; CI 0.86-1.33), and neither were changes in gross domestic product (RR 1.29; CI 0.94-1.79) or balance of trade (RR 1.08; CI 0.96-1.22). Conclusion: The economic collapse and rising unemployment rates in Iceland did not result in an overall increase in suicide rates. A strong welfare system and investing in social protection during the economic crisis may have mitigated suicide risk.
Promoter Methylation Status in 1031 Primary Breast Cancers Predicts Favorable Outcomes Following Chemotherapy.Background: Breast Cancer 1 gene (BRCA1) is known to be inactivated in breast tumors by promoter methylation. Tumor cells in patients carrying a germline mutation in BRCA1 are sensitive to cytotoxic drugs that cause DNA double strand breaks. However, very little is known on whether patients with BRCA1 promoter methylated tumors are similarly sensitive to cytotoxic drugs. In this study, we address this by making use of extensive follow-up data on patients treated with cyclophosphamide, methotrexate, and fluorouracil in Iceland between 1976 and 2007. Methods: We analyzed BRCA1 promoter methylation by pyrosequencing DNA from tumor samples from 1031 patients with primary breast cancer. Of those, 965 were sporadic cases, 61 were BRCA2, and five were BRCA1 germline mutation carriers. All cases were examined with respect to clinicopathological parameters and breast cancer-specific survival in patients treated with cytotoxic drugs. Information on chemotherapy treatment in noncarriers was available for 26 BRCA1 methylated tumors and 857 unmethylated tumors. Results: BRCA1 was promoter methylated in 29 sporadic tumors or in 3.0% of cases (29 of 965), whereas none of the tumors derived from BRCA germline mutation carriers were promoter methylated. Important to note, patients with BRCA1 promoter methylation receiving chemotherapeutic drug treatment show highly improved breast cancer-specific survival compared with unmethylated controls (hazard ratio = 0.10, 95% confidence interval = 0.01 to 0.75, two-sided P = .02). Conclusions: BRCA1 promoter methylation is predictive of improved disease outcome in patients receiving cyclophosphamide, methotrexate, and fluorouracil drug treatment. Our results support the use of markers indicative of "BRCAness" in sporadic breast cancers to identify patients that are likely to benefit from the use of DNA-damaging agents.