Microarray Technology May Reveal the Contribution of Allergen Exposure and Rhinovirus Infections as Possible Triggers for Acute Wheezing Attacks in Preschool Children

Allergen exposure and rhinovirus (RV) infections are common triggers of acute wheezing exacerbations in early childhood. The identification of such trigger factors is difficult but may have therapeutic implications. Increases of IgE and IgG in sera, were shown against allergens and the N-terminal portion of the VP1 proteins of RV species, respectively, several weeks after allergen exposure or RV infection. Hence, increases in VP1-specific IgG and in allergen-specific IgE may serve as biomarkers for RV infections or allergen exposure. The MeDALL-allergen chip containing comprehensive panels of allergens and the PreDicta RV chip equipped with VP1-derived peptides, representative of three genetic RV species, were used to measure allergen-specific IgE levels and RV-species-specific IgG levels in sera obtained from 120 preschool children at the time of an acute wheezing attack and convalescence. Nearly 20% of the children (22/120) showed specific IgE sensitizations to at least one of the allergen molecules on the MeDALL chip. For 87% of the children, increases in RV-specific IgG could be detected in the follow-up sera. This percentage of RV-specific IgG increases was equal in IgE-positive and -negative children. In 10% of the children, increases or de novo appearances of IgE sensitizations indicative of allergen exposure could be detected. Our results suggest that, in the majority of preschool children, RV infections trigger wheezing attacks, but, in addition, allergen exposure seems to play a role as a trigger factor. RV-induced wheezing attacks occur in IgE-sensitized and non-IgE-sensitized children, indicating that allergic sensitization is not a prerequisite for RV-induced wheeze.     

Relative Validity of Micronutrient and Fiber Intake Assessed With Two New Interactive Meal- and Web-Based Food Frequency Questionnaires

Background

The meal- and Web-based food frequency questionnaires, Meal-Q and MiniMeal-Q, were developed for cost-efficient assessment of dietary intake in epidemiological studies.

Objective

The objective of this study was to evaluate the relative validity of micronutrient and fiber intake assessed with Meal-Q and MiniMeal-Q. The reproducibility of Meal-Q was also evaluated.

Methods

A total of 163 volunteer men and women aged between 20 and 63 years were recruited from Stockholm County, Sweden. Assessment of micronutrient and fiber intake with the 174-item Meal-Q was compared to a Web-based 7-day weighed food record (WFR). Two administered Meal-Q questionnaires were compared for reproducibility. The 126-item MiniMeal-Q, developed after the validation study, was evaluated in a simulated validation by using truncated Meal-Q data.

Results

The study population consisted of approximately 80% women (129/163) with a mean age of 33 years (SD 12) who were highly educated (130/163, 80% with >12 years of education) on average. Cross-classification of quartiles with the WFR placed 69% to 90% in the same/adjacent quartile for Meal-Q and 67% to 89% for MiniMeal-Q. Bland-Altman plots with the WFR and the questionnaires showed large variances and a trend of increasing underestimation with increasing intakes. Deattenuated and energy-adjusted Spearman rank correlations between the questionnaires and the WFR were in the range ρ=.25-.69, excluding sodium that was not statistically significant. Cross-classifications of quartiles of the 2 Meal-Q administrations placed 86% to 97% in the same/adjacent quartile. Intraclass correlation coefficients for energy-adjusted intakes were in the range of .50-.76.

Conclusions

With the exception of sodium, this validation study demonstrates Meal-Q and MiniMeal-Q to be useful methods for ranking micronutrient and fiber intake in epidemiological studies with Web-based data collection.     

Effects of Walking Speed on Total and Regional Body Fat in Healthy Postmenopausal Women

Introduction: This study had two aims: (1) To confirm the efficacy of exercise speed and impulse (session duration at a given speed) to produce total and abdominal fat loss in postmenopausal women, and (2) compare the exercise speed and impulse necessary for the stimulation of fat loss to the suppression of bone mineral loss. Of special interest was to compare these parameters of exercise on fat loss in the same study and with the same subjects where they were found to suppress bone mineral loss. We hypothesized that (1) more total fat will be lost with slow walking and a longer impulse than with fast speed and shorter impulse, and (2) more abdominal subcutaneous (SC) and visceral fat (VF) will be lost with fast walking speed. Materials and Methods: Fat loss and suppression of bone mineral loss were measured in the same 25 subjects after 15 weeks, and fat measurements were also taken after 30 weeks in 16 residual subjects. Study parameters were walking a 4.8 km distance 4 days/week at either 6.6 km/h (120% of ventilatory threshold (VT)) or at 5.5 km/h (101.6% of VT) and expending 300 kcal/session. Body composition (fat and lean body mass, LBM) was measured with dual-energy X-ray absorptiometry (DXA) and anthropometric methods. Results: Slow walkers in the residual group progressively lost a significant percent of total body fat over 30 weeks while no such loss occurred after 15 weeks in fast walkers in either group, supporting hypothesis 1. However, the 20% higher starting body fat in 16 residual slow relative to fast subjects suggests that exercise fat loss is greater in overweight than in lean subjects. In fast walkers, fat loss occurred after 30 weeks of training. Hypothesis 2 was not supported as both speeds led to equal VF loss in 30-week group as estimated by waist circumference (CF) confirming that VF responds to the magnitude of energy expenditure and not the walking speed. Conclusions: Total body fat is lost through walking at all speeds, but the change is more rapid, clear, and initially greater with slow walking in overweight subjects. A longer exercise impulse at a lower speed in our study initially produced greater total fat loss than a shorter one with fast walking speed. This was reversed in comparison to how the same exercise in the same subjects suppressed bone mineral loss. Data from other studies indicate that longer impulses may promote greater fat loss at both slow and high exercise speeds, and our study providing only a 4.8 km walking distance may have limited the walking impulse and the magnitude of fat loss. Increased exercise energy expenditure at either walking speed produces equivalent declines in visceral fat in postmenopausal women, and with sufficiently long impulses, should reduce disabilities associated with central obesity.     

Dietary intake of phytoestrogens, estrogen receptor-beta polymorphisms and the risk of prostate cancer

BACKGROUND: The causes of prostate cancer are poorly understood, but genetic factors may be more important than for many other malignancies, and dietary phytoestrogens may be protective. Because phytoestrogens bind tightly to the estrogen receptor-beta, we conducted an epidemiologic investigation of synergistic effects between phytoestrogen intake and estrogen receptor-beta gene polymorphisms. METHODS: We performed a population-based case-control study in Sweden. All participants reported their phytoestrogen intake and donated a blood sample. We identified four haplotype-tagging single nucleotide polymorphisms (htSNPs) and genotyped these htSNPs in 1314 prostate cancer patients and 782 controls. Odds ratios were estimated by multivariate logistic regression. Interactions between phytoestrogen intake and estrogen receptor-beta SNPs on prostate cancer risk were evaluated considering both multiplicative and additive effect scales. RESULTS: We found a significant multiplicative interaction (P = 0.04) between dietary intake of phytoestrogens and a promoter SNP in the estrogen receptor-beta gene (rs 2987983-13950), but not with any of the three other htSNPs (P = 0.11, 0.69, 0.85). Among carriers of the variant promoter alleles, we found strong inverse associations with increasing intake of total phytoestrogens (odds ratio for highest vs. lowest quartile = 0.43; P for trend <0.001), isoflavonoids (odds ratio = 0.63; P for trend = 0.05), and coumestrol (odds ratio = 0.57; P for trend = 0.003). We found no association between phytoestrogens and prostate cancer among carriers homozygous for the wild-type allele (TT). CONCLUSIONS: Our study provides strong evidence that high intake of phytoestrogens substantially reduce prostate cancer risk among men with specific polymorphic variation in the promoter region of the estrogen receptor-beta gene.     

Serotonin 1B receptor density mapping of the human brainstem using positron emission tomography and autoradiography

The serotonin 1B (5-HT_1B) receptor has lately received considerable interest in relation to psychiatric and neurological diseases, partly due to findings based on quantification using Positron Emission Tomography (PET). Although the brainstem is an important structure in this regard, PET radioligand binding quantification in brainstem areas often shows poor reliability. This study aims to improve PET quantification of 5-HT_1B receptor binding in the brainstem.Volumes of interest (VOIs) were selected based on a 3D [³H]AZ10419369 Autoradiography brainstem model, which visualized 5-HT_1B receptor distribution in high resolution. Two previously developed VOI delineation methods were tested and compared to a conventional manual method. For a method based on template data, a [¹¹C]AZ10419369 PET template was created by averaging parametric binding potential (BP_ND) images of 52 healthy subjects. VOIs were generated based on a predefined volume and BP_ND thresholding and subsequently applied to test-retest [¹¹C]AZ10419369 parametric BP_ND images of 8 healthy subjects. For a method based on individual subject data, VOIs were generated directly on each individual parametric image.Both methods showed improved reliability compared to a conventional manual VOI. The VOIs created with [¹¹C]AZ10419369 template data can be automatically applied to future PET studies measuring 5-HT_1B receptor binding in the brainstem.     

The RUSH2A Study: Dark-Adapted Visual Fields in Patients With Retinal Degeneration Associated With Biallelic Variants in the USH2A Gene

PurposeTo measure visual fields using two-color dark-adapted chromatic perimetry in a subset of participants in the Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A), a study of USH2A-mediated syndromic (USH2) and autosomal recessive nonsyndromic retinitis pigmentosa, determine percentage retaining rod function, and explore relationships between dark-adapted visual fields (DAVF) and rod function from ERG and full-field stimulus thresholds (FST).MethodsFull-field rod mean sensitivity, number of rod loci, maximum sensitivity, DAVF full-field hill of vision (DAVF V_TOT), and 30° hill of vision (DAVF V₃₀) were measured in one eye for DAVF ancillary study participants (n = 49). Loci where cyan relative to red sensitivity was more than 5 dB on dark-adapted chromatic perimetry were considered rod mediated. Correlation coefficients between the DAVF measures and standard clinical measures were estimated, as were kappa statistics (κ) for agreement between DAVF and other measures of rod function.ResultsOf 49 participants tested with DAVF, 38 (78%) had evidence of rod function, whereas 15 (31%) had measurable rod ERGs. DAVF maximum sensitivity was highly correlated with FST white thresholds (r = −0.80; P < .001). Although not statistically significant, the number of rod loci and DAVF V_TOT were lower in eyes with longer disease duration by 0.82 (95% confidence interval, −1.76, 0.12) loci/year and 0.59 (95% confidence interval, −1.82, 0.64) dB-steradians/year, respectively.ConclusionsRod-mediated function on FST and DAVF is present in many patients with symptomatic USH2A-related retinal degeneration, including some without measurable rod ERGs. RUSH2A longitudinal data will determine how these measures change with disease progression and whether they are useful for longitudinal studies in inherited retinal degenerations.