The house dust mite (HDM) is a major perennial allergen source and a significant cause of allergic rhinitis and allergic asthma. However, awareness of the condition remains generally low. This review ...assesses the links between exposure to HDM, development of the allergic response, and pathologic consequences in patients with respiratory allergic diseases. We investigate the epidemiology of HDM allergy to explore the interaction between mites and human subjects at the population, individual, and molecular levels. Core and recent publications were identified by using “house dust mite” as a key search term to evaluate the current knowledge of HDM epidemiology and pathophysiology. Prevalence data for HDM allergen sensitization vary from 65 to 130 million persons in the general population worldwide to as many as 50% among asthmatic patients. Heterogeneity of populations, terminology, and end points in the literature confound estimates, indicating the need for greater standardization in epidemiologic research. Exposure to allergens depends on multiple ecological strata, including climate and mite microhabitats within the domestic environment, with the latter providing opportunity for intervention measures to reduce allergen load. Inhaled mite aeroallergens are unusually virulent: they are able to activate both the adaptive and innate immune responses, potentially offering new avenues for intervention. The role of HDM allergens is crucial in the development of allergic rhinitis and asthma, but the translation of silent sensitization into symptomatic disease is still incompletely understood. Improved understanding of HDMs, their allergens, and their microhabitats will enable development of more effective outcomes for patients with HDM allergy.
Quantitative changes in leptin concentration lead to alterations in food intake and body weight, but the regulatory mechanisms that control leptin gene expression are poorly understood. Here we ...report that fat-specific and quantitative leptin expression is controlled by redundant cis elements and trans factors interacting with the proximal promoter together with a long noncoding RNA (lncOb). Diet-induced obese mice lacking lncOb show increased fat mass with reduced plasma leptin levels and lose weight after leptin treatment, whereas control mice do not. Consistent with this finding, large-scale genetic studies of humans reveal a significant association of single-nucleotide polymorphisms (SNPs) in the region of human lncOb with lower plasma leptin levels and obesity. These results show that reduced leptin gene expression can lead to a hypoleptinemic, leptin-responsive form of obesity and provide a framework for elucidating the pathogenic mechanism in the subset of obese patients with low endogenous leptin levels.
Recent global developments underscore the prominent role big data have in modern medical science. But privacy issues constitute a prevalent problem for collecting and sharing data between ...researchers. However, synthetic data generated to represent real data carrying similar information and distribution may alleviate the privacy issue. In this study, we present generative adversarial networks (GANs) capable of generating realistic synthetic DeepFake 10-s 12-lead electrocardiograms (ECGs). We have developed and compared two methods, named WaveGAN* and Pulse2Pulse. We trained the GANs with 7,233 real normal ECGs to produce 121,977 DeepFake normal ECGs. By verifying the ECGs using a commercial ECG interpretation program (MUSE 12SL, GE Healthcare), we demonstrate that the Pulse2Pulse GAN was superior to the WaveGAN* to produce realistic ECGs. ECG intervals and amplitudes were similar between the DeepFake and real ECGs. Although these synthetic ECGs mimic the dataset used for creation, the ECGs are not linked to any individuals and may thus be used freely. The synthetic dataset will be available as open access for researchers at OSF.io and the DeepFake generator available at the Python Package Index (PyPI) for generating synthetic ECGs. In conclusion, we were able to generate realistic synthetic ECGs using generative adversarial neural networks on normal ECGs from two population studies, thereby addressing the relevant privacy issues in medical datasets.
The indigenous people of Greenland, the Inuit, have lived for a long time in the extreme conditions of the Arctic, including low annual temperatures, and with a specialized diet rich in protein and ...fatty acids, particularly omega-3 polyunsaturated fatty acids (PUFAs). A scan of Inuit genomes for signatures of adaptation revealed signals at several loci, with the strongest signal located in a cluster of fatty acid desaturases that determine PUFA levels. The selected alleles are associated with multiple metabolic and anthropometric phenotypes and have large effect sizes for weight and height, with the effect on height replicated in Europeans. By analyzing membrane lipids, we found that the selected alleles modulate fatty acid composition, which may affect the regulation of growth hormones. Thus, the Inuit have genetic and physiological adaptations to a diet rich in PUFAs.
Abstract
Context
The lack of sensitive and robust analytical methods has hindered the reliable quantification of estrogen metabolites in subjects with low concentrations.
Objective
To establish ...sex-specific reference ranges for estrone (E1) and estradiol (E2) throughout life and to evaluate sex-differences using the state-of-the-art liquid chromatography tandem mass spectrometry (LC-MS/MS) method for quantification of E1, E2, and estriol (E3).
Design
LC-MS/MS method development and construction of estrogen reference ranges.
Settings
Population-based cross-sectional cohorts from the greater Copenhagen and Aarhus areas.
Participants
Healthy participants aged 3 months to 61 years (n = 1838).
Results
An isotope diluted LC-MS/MS method was developed and validated for measurements of serum E1, E2, and E3. Limits of detections (LODs) were 3 pmol/L (E1), 4 pmol/L (E2), and 12 pmol/L (E3), respectively. This sensitive method made it possible to differentiate between male and female concentration levels of E1 and E2 in children. In girls, E2 levels ranged from <LOD to 100 pmol/L during mini-puberty, whereas it was ≤20 pmol/L during childhood. E1 and E2 increased with age and pubertal breast stage and varied during the menstrual cycle; E1 was lower than E2 in girls and premenopausal women, and higher than E2 in postmenopausal women. In boys, E1 and E2 increased with age and pubertal stage, whereas little changes with age were observed in men. High E3 concentrations were confirmed in pregnant women.
Conclusion
Reference ranges of simultaneous quantification of E1 and E2 by this novel specific and highly sensitive LC-MS/MS method provide an invaluable tool in clinical practice and in future research studies.
Abstract
Deep learning-based tools may annotate and interpret medical data more quickly, consistently, and accurately than medical doctors. However, as medical doctors are ultimately responsible for ...clinical decision-making, any deep learning-based prediction should be accompanied by an explanation that a human can understand. We present an approach called electrocardiogram gradient class activation map (ECGradCAM), which is used to generate attention maps and explain the reasoning behind deep learning-based decision-making in ECG analysis. Attention maps may be used in the clinic to aid diagnosis, discover new medical knowledge, and identify novel features and characteristics of medical tests. In this paper, we showcase how ECGradCAM attention maps can unmask how a novel deep learning model measures both amplitudes and intervals in 12-lead electrocardiograms, and we show an example of how attention maps may be used to develop novel ECG features.
Numerous studies have investigated the prevalence and risk factors of hand eczema in the general population. These studies are of high value as they tend to be less biased than studies using clinical ...populations and as they are important for healthcare decision makers when they allocate resources. This study aimed to review the epidemiology of hand eczema in the general population.
Literature was examined using Pubmed‐Medline, Biosis, Science Citation Index, and dermatology text books. On the basis of studies performed between 1964 and 2007, the point prevalence of hand eczema was around 4%, the 1‐year prevalence nearly 10%, whereas the lifetime prevalence reached 15%. Based on seven studies, the median incidence rate of hand eczema was 5.5 cases/1000 person‐years (women = 9.6 and men = 4.0). A high incidence rate was associated with female sex, contact allergy, atopic dermatitis, and wet work. Atopic dermatitis was the single most important risk factor for hand eczema. Hand eczema resulted in medical consultations in 70%, sick leave (> 7 days) in about 20%, and job change in about 10%. Mean sick time was longer among those with allergic hand eczema than those with atopic and irritant hand eczema. Moderate to severe extension of hand eczema was the strongest risk factor for persistence of hand eczema. Other risk factors included early onset of hand eczema and childhood eczema. The aetiology of hand eczema is multifactorial and includes environmental as well as genetic factors. Future studies should focus on unresolved areas of hand eczema, for example, genetic predisposition.
Background Maternal supplementation with long-chain n-3 polyunsaturated fatty acids can have immunologic effects on the developing fetus through several anti-inflammatory pathways. However, there is ...limited knowledge of the long-term programming effects. Objective In a randomized controlled trial from 1990 with 24 years of follow-up, our aim was to determine whether supplementation with 2.7 g of long-chain n-3 polyunsaturated fatty acids in pregnancy can reduce the risk of asthma in offspring and allergic respiratory disease. Methods The randomized controlled trial included 533 women who were randomly assigned to receive fish oil during the third trimester of pregnancy, olive oil, or no oil in the ratio 2:1:1. The offspring were followed in a mandatory national prescription register, with complete follow-up for prescriptions related to the treatment of asthma and allergic rhinitis as primary outcomes. Furthermore, the offspring were invited to complete a questionnaire (74% participated) and attend a clinical examination (47% participated) at age 18 to 19 years. Results In intention-to-treat analyses the probability of having had asthma medication prescribed was significantly reduced in the fish oil group compared with the olive oil group (hazard ratio, 0.54, 95% CI, 0.32-0.90; P = .02). The probability of having had allergic rhinitis medication prescribed was also reduced in the fish oil group compared with the olive oil group (hazard ratio, 0.70, 95% CI, 0.47-1.05; P = .09), but the difference was not statistically significant. Self-reported information collected at age 18 to 19 years supported these findings. No associations were detected with respect to lung function outcomes or allergic sensitization at 18 to 19 years of age. Conclusion Maternal supplementation with fish oil might have prophylactic potential for long-term prevention of asthma in offspring.
The Greenlandic population, a small and historically isolated founder population comprising about 57,000 inhabitants, has experienced a dramatic increase in type 2 diabetes (T2D) prevalence during ...the past 25 years. Motivated by this, we performed association mapping of T2D-related quantitative traits in up to 2,575 Greenlandic individuals without known diabetes. Using array-based genotyping and exome sequencing, we discovered a nonsense p.Arg684Ter variant (in which arginine is replaced by a termination codon) in the gene TBC1D4 with an allele frequency of 17%. Here we show that homozygous carriers of this variant have markedly higher concentrations of plasma glucose (β = 3.8 mmol l(-1), P = 2.5 × 10(-35)) and serum insulin (β = 165 pmol l(-1), P = 1.5 × 10(-20)) 2 hours after an oral glucose load compared with individuals with other genotypes (both non-carriers and heterozygous carriers). Furthermore, homozygous carriers have marginally lower concentrations of fasting plasma glucose (β = -0.18 mmol l(-1), P = 1.1 × 10(-6)) and fasting serum insulin (β = -8.3 pmol l(-1), P = 0.0014), and their T2D risk is markedly increased (odds ratio (OR) = 10.3, P = 1.6 × 10(-24)). Heterozygous carriers have a moderately higher plasma glucose concentration 2 hours after an oral glucose load than non-carriers (β = 0.43 mmol l(-1), P = 5.3 × 10(-5)). Analyses of skeletal muscle biopsies showed lower messenger RNA and protein levels of the long isoform of TBC1D4, and lower muscle protein levels of the glucose transporter GLUT4, with increasing number of p.Arg684Ter alleles. These findings are concomitant with a severely decreased insulin-stimulated glucose uptake in muscle, leading to postprandial hyperglycaemia, impaired glucose tolerance and T2D. The observed effect sizes are several times larger than any previous findings in large-scale genome-wide association studies of these traits and constitute further proof of the value of conducting genetic association studies outside the traditional setting of large homogeneous populations.
Background High pre-pregnancy body mass index (BMI) and excessive gestational weight gain (GWG) are suggested to influence risk of asthma and atopic disease in offspring. Objective We examined the ...effect of BMI and GWG on risk of asthma, wheezing, atopic eczema (AE), and hay fever in children during the first 7 years of life. Methods This was a cohort study of 38,874 mother-child pairs from the Danish National Birth Cohort (enrollment 1996-2002) with information from the 16th week of pregnancy and at age 6 months, 18 months, and 7 years of the child. Odds ratios (ORs) with 95% CIs were calculated by logistic regression with adjustment for potential confounders. Results During the first 7 years of life, 10.4% of children developed doctor-diagnosed asthma, 25.8% AE, and 4.6% hay fever. Maternal BMI and to a lesser extent GWG were associated with doctor-diagnosed asthma ever. In particular, BMI ≥ 35 (adjusted OR, 1.87; 95% CI, 0.95-3.68) and GWG ≥ 25 kg (adjusted OR, 1.97; 95% CI, 1.38-2.83) were associated with current severe asthma at age 7 years. Maternal BMI was also associated with wheezing in offspring, with the strongest association observed between BMI ≥ 35 and late-onset wheezing (adjusted OR, 1.87; 95% CI, 1.28-2.73). Maternal BMI and GWG were not associated with AE or hay fever. Conclusions Maternal obesity during pregnancy was associated with increased risk of asthma and wheezing in offspring but not with AE and hay fever, suggesting that pathways may be nonallergic.
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