Use of baked milk challenges and milk ladders in clinical practice:a worldwide survey of healthcare professionals

In previous years, the cornerstone of the management of Cow's Milk Allergy (CMA) was solely based on the strict avoidance of all cow's milk (CM) and foods containing CM from the patient's diet [1]. More recently, the importance of baked milk (BM) introduction into the diet of children with CMA has become well-recognised as a part of CMA management. Current research suggests that 75% of children become tolerant to baked/heated forms of CM such as muffin and waffles before they become tolerant to pure/uncooked forms of CM [2]

Peanut allergy:effect of environmental peanut exposure in children with filaggrin loss-of-function mutations

BackgroundFilaggrin (FLG) loss-of-function mutations lead to an impaired skin barrier associated with peanut allergy. Household peanut consumption is associated with peanut allergy, and peanut allergen in household dust correlates with household peanut consumption.ObjectiveWe sought to determine whether environmental peanut exposure increases the odds of peanut allergy and whether FLG mutations modulate these odds.MethodsExposure to peanut antigen in dust within the first year of life was measured in a population-based birth cohort. Peanut sensitization and peanut allergy (defined by using oral food challenges or component-resolved diagnostics [CRD]) were assessed at 8 and 11 years. Genotyping was performed for 6 FLG mutations.ResultsAfter adjustment for infantile atopic dermatitis and preceding egg skin prick test (SPT) sensitization, we found a strong and significant interaction between natural log (ln [loge]) peanut dust levels and FLG mutations on peanut sensitization and peanut allergy. Among children with FLG mutations, for each ln unit increase in the house dust peanut protein level, there was a more than 6-fold increased odds of peanut SPT sensitization, CRD sensitization, or both in children at ages 8 years, 11 years, or both and a greater than 3-fold increased odds of peanut allergy compared with odds seen in children with wild-type FLG. There was no significant effect of exposure in children without FLG mutations. In children carrying an FLG mutation, the threshold level for peanut SPT sensitization was 0.92 μg of peanut protein per gram (95% CI, 0.70-1.22 μg/g), that for CRD sensitization was 1.03 μg/g (95% CI, 0.90-1.82 μg/g), and that for peanut allergy was 1.17 μg/g (95% CI, 0.01-163.83 μg/g).ConclusionEarly-life environmental peanut exposure is associated with an increased risk of peanut sensitization and allergy in children who carry an FLG mutation. These data support the hypothesis that peanut allergy develops through transcutaneous sensitization in children with an impaired skin barrier

On-Line Detection And Measurement Of Partial Discharge Signals In A Noisy Environment

In extracting partial discharge (PD) signals embedded in excessive noise, the need for an online and automated tool becomes a crucial necessity. One of the recent approaches that have gained some acceptance within the research arena is the Wavelet multi-resolution analysis (WMRA). However selecting an accurate mother wavelet, defining dynamic threshold values and identifying the resolution levels to be considered in the PD extraction from the noise are still challenging tasks. This paper proposes a novel wavelet-based technique for extracting PD signals embedded in high noise levels. The proposed technique enhances the WMRA by decomposing the noisy data into different resolution levels while sliding it into Kaiser's window. Only the maximum expansion coefficients at each resolution level are used in de-noising and measuring the extracted PD signal. A small set of coefficients is used in the monitoring process without assigning threshold values or performing signal reconstruction. The proposed monitoring technique has been applied to a laboratory data as well as to a simulated PD pulses embedded in a collected laboratory noise

Mutation of the Glucosinolate Biosynthesis Enzyme Cytochrome P450 83A1 Monooxygenase Increases Camalexin Accumulation and Powdery Mildew Resistance

Small secondary metabolites, including glucosinolates and the major phytoalexin camalexin, play important roles in immunity in Arabidopsis thaliana. We isolated an Arabidopsis mutant with increased resistance to the powdery mildew fungus Golovinomyces cichoracearum and identified a mutation in the gene encoding cytochrome P450 83A1 monooxygenase (CYP83A1), which functions in glucosinolate biosynthesis. The cyp83a1-3 mutant exhibited enhanced defense responses to G. cichoracearum and double mutant analysis showed that this enhanced resistance requires NPR1, EDS1, and PAD4, but not SID2 or EDS5. In cyp83a1-3 mutants, the expression of genes related to camalexin synthesis increased upon G. cichoracearum infection. Significantly, the cyp83a1-3 mutant also accumulated higher levels of camalexin. Decreasing camalexin levels by mutation of the camalexin synthetase gene PAD3 or the camalexin synthesis regulator AtWRKY33 compromised the powdery mildew resistance in these mutants. Consistent with these observations, overexpression of PAD3 increased camalexin levels and enhanced resistance to G. cichoracearum. Taken together, our data indicate that accumulation of higher levels of camalexin contributes to increased resistance to powdery mildew

Mitochondrial ferritin deficiency reduces male fertility in mice

Mitochondrial ferritin (FtMt) is a functional ferritin targeted to mitochondria that is highly expressed in the testis. To investigate the role of FtMt in the testis we set up a series of controlled matings between FtMt gene-deletion mice (FtMt–/–) with FtMt+/+ mice. We found that the number of newborns per litter and the fertility rate were strongly reduced for the FtMt–/– males, but not for the females, indicating that FtMt has an important role for male fertility. The morphology of the testis and of the spermatozoa of FtMt–/– mice was normal and we did not detect alterations in sperm parameters or in oxidative stress indices. In contrast, we observed that the cauda epididymides of FtMt–/– mice were significantly lighter and contained a lower number of spermatozoa compared with the controls. Also, the ATP content of FtMt–/– spermatozoa was found to be lower than that of FtMt+/+ spermatozoa. These data show that FtMt contributes to sperm epididymis maturation and to male fertility.The work was partially supported by MIUR grant PRIN10–11 to P. A. and by Telethon grant GGP1099 to P. A

The NorR Regulon Is Critical for Vibrio cholerae Resistance to Nitric Oxide and Sustained Colonization of the Intestines

Vibrio cholerae, the cause of an often fatal infectious diarrhea, remains a large global public health threat. Little is known about the challenges V. cholerae encounters during colonization of the intestines, which genes are important for overcoming these challenges, and how these genes are regulated. In this study, we examined the V. cholerae response to nitric oxide (NO), an antibacterial molecule derived during infection from various sources, including host inducible NO synthase (iNOS). We demonstrate that the regulatory protein NorR regulates the expression of NO detoxification genes hmpA and nnrS, and that all three are critical for resisting low levels of NO stress under microaerobic conditions in vitro. We also show that prxA, a gene previously thought to be important for NO detoxification, plays no role in NO resistance under microaerobic conditions and is upregulated by H2O2, not NO. Furthermore, in an adult mouse model of prolonged colonization, hmpA and norR were important for the resistance of both iNOS- and non-iNOS-derived stresses. Our data demonstrate that NO detoxification systems play a critical role in the survival of V. cholerae under microaerobic conditions resembling those of an infectious setting and during colonization of the intestines over time periods similar to that of an actual V. cholerae infection

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Atopic dermatitis increases the effect of exposure to peanut antigen in dust on peanut sensitization and likely peanut allergy

BackgroundHistory and severity of atopic dermatitis (AD) are risk factors for peanut allergy. Recent evidence suggests that children can become sensitized to food allergens through an impaired skin barrier. Household peanut consumption, which correlates strongly with peanut protein levels in household dust, is a risk factor for peanut allergy.ObjectiveWe sought to assess whether environmental peanut exposure (EPE) is a risk for peanut sensitization and allergy and whether markers of an impaired skin barrier modify this risk.MethodsPeanut protein in household dust (in micrograms per gram) was assessed in highly atopic children (age, 3-15 months) recruited to the Consortium of Food Allergy Research Observational Study. History and severity of AD, peanut sensitization, and likely allergy (peanut-specific IgE, ≥5 kUA/mL) were assessed at recruitment into the Consortium of Food Allergy Research study.ResultsThere was an exposure-response relationship between peanut protein levels in household dust and peanut skin prick test (SPT) sensitization and likely allergy. In the final multivariate model an increase in 4 log2 EPE units increased the odds of peanut SPT sensitization (1.71-fold; 95% CI, 1.13- to 2.59-fold; P = .01) and likely peanut allergy (PA; 2.10-fold; 95% CI, 1.20- to 3.67-fold; P < .01). The effect of EPE on peanut SPT sensitization was augmented in children with a history of AD (OR, 1.97; 95% CI, 1.26-3.09; P < .01) and augmented even further in children with a history of severe AD (OR, 2.41; 95% CI, 1.30-4.47; P < .01); the effect of EPE on PA was also augmented in children with a history of AD (OR, 2.34; 95% CI, 1.31-4.18; P < .01).ConclusionExposure to peanut antigen in dust through an impaired skin barrier in atopically inflamed skin is a plausible route for peanut SPT sensitization and PA

Early-life regional and temporal variation in filaggrin-derived natural moisturizing factor, filaggrin-processing enzyme activity, corneocyte phenotypes and plasmin activity:Implications for atopic dermatitis

Background: Filaggrin is central to the pathogenesis of atopic dermatitis (AD). The cheeks are a common initiation site of infantile AD. Regional and temporal expression of levels of filaggrin degradation products [natural moisturizing factors (NMFs)], activities of filaggrin‐processing enzymes [bleomycin hydrolase (BH) and calpain‐1 (C‐1)] and plasmin, and corneocyte envelope (CE) maturity in early life are largely unknown. / Objectives: We conducted a cross‐sectional, observational study investigating regional and age‐dependent variations in NMF levels, activity of proteases and CE maturity in stratum corneum (SC) from infants to determine whether these factors could explain the observed predilection sites for AD in early life. / Methods: We measured NMF using a tape‐stripping method at seven sites in the SC of 129 children (aged < 12 months to 72 months) and in three sites in 56 neonates and infants (< 48 h to 3 months). In 37 of these neonates and infants, corneocyte size, maturity, BH, C‐1 and plasmin activities were determined. / Results: NMF levels are low at birth and increase with age. Cheek SC, compared with elbow flexure and nasal tip, has the lowest NMF in the first year of life and is the slowest to reach stable levels. Cheek corneocytes remain immature. Plasmin, BH and C‐1 activities are all elevated by 1 month of age in exposed cheek skin, but not in elbow skin. / Conclusions: Regional and temporal differences in NMF levels, CE maturity and protease activities may explain the predilection for AD to affect the cheeks initially and are supportive of this site as key for allergen priming in early childhood. These observations will help design early intervention and treatment strategies for AD