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Background: In children, fruit and vegetable allergies are often overlooked compared with well-known allergies such as those to eggs, milk, and shellfish. Therefore, this study aimed to analyze fruit and vegetable allergies in children, including prevalence, types of food allergens, clinical presentation, management, and associated comorbid atopic diseases., Methods: In 2012, a nationwide, cross-sectional, random sampling questionnaire-based survey for common fruit and vegetable allergies was conducted in Taiwan. Information regarding these plant food allergies was collected. Physicians diagnosed food allergies according to the descriptions of convincing symptoms. Enrolled questionnaires were reviewed by expert pediatricians., Results: A total of 9,982 valid questionnaires were analyzed. The overall prevalence of fruit and vegetable allergies was 5.6% (n = 560) and 3.0% (n = 304), respectively. The most common fruit allergen was mango, followed by kiwifruit, whereas taro and bamboo shoot were the most common vegetable allergens. Meanwhile, most allergic symptoms were of the mucocutaneous tissue, followed by the upper airway and gastrointestinal tract. Most only required avoidance of allergens and not medical treatment. Children with fruit or vegetable allergies had a higher percentage of comorbid atopic dermatitis, allergic rhinitis, and asthma than those without food allergies; additionally, the proportion of comorbid atopic diseases was similar between fruit and vegetable allergies and shellfish allergy. One child developed anaphylaxis due to a corn allergy., Conclusions: Fruits and vegetables are common food allergens in Taiwanese children who present with diverse and potentially severe symptoms. Children with plant food allergies had a percentage of comorbid atopic diseases similar to that of shellfish allergy, the most common allergen. These findings indicate the importance of considering fruit and vegetable allergies in children., (Copyright © 2022 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

The occurrence of egg proteins in products containing spent fowl manufactured under current practices was studied to assess the risk these food products may pose to egg-allergic consumers and to determine if Precautionary Allergen Labelling (PAL) was recommended. Spent fowl slaughtering and processing operations in 2 Canadian facilities were observed. Raw hen pieces (n = 134), coming from 2 facilities, and intermediate and processed products containing spent fowl (n = 57), coming from one facility, were analyzed using ELISA. All samples tested positive for egg proteins. Raw pieces were tested using a qualitative method (i.e., swabbing); estimated egg proteins concentrations suggest the presence of highly contaminated samples (>600 mg/kg in 2 hen wing samples). Swabbing was found to be efficient for rapid detection of eggs in raw hen pieces, but not for quantification. A comparison between swab and grind results showed that egg proteins concentration is underestimated by at least a factor 2 for whole carcasses and a factor 10 for breast, wings and drumsticks, when using the swab protocol. For intermediate and processed products, quantitative measurements indicate that egg protein levels were below 16 mg/kg. Additionally, 88 water samples from chiller tanks were analyzed and indicate that this step could be the cause of the global contamination observed with an increase in egg protein concentrations overtime during the production schedule. As egg contamination is not adequately controlled under the current good production practices, the use of PAL would be recommended for raw spent fowl products., Competing Interests: Disclosures This work was supported through funding from the Food Regulatory Platform Fund, part of the Trust fund of Laval University, and specifically through contributions and donations provided by the Canadian Poultry and Egg Processors Council to the trust fund. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

In this study, a novel and green chitosan-metformin/NiCl 2 /Fe 3 O 4 nanobiocomposite was synthesized and used to purify alkaline phosphatase (ALPs) from hen's egg yolk. For this purpose, after functionalization of the chitosan biopolymer by terephthaloyl chloride-metformin ligand, the coordination with Ni(II) and magnetization process were performed. The structure and properties of the synthesized nanobiocomposite were then evaluated by using analyzes such as FT-IR, EDX, FE-SEM, XRD, TGA and VSM. Purification of ALPs with chitosan-metformin/NiCl 2 /Fe 3 O 4 nanobiocomposite is a fast, reusable and cost-effective method. By this protocol, 62% purification efficiency was obtained and the synthesized nanobiocomposite was not attached to other proteins in hen's egg yolk. ALPs was obtained approximately in the pure form and the purification process was evaluated using SDS-PAGE. The reusability of nanobiocomposites was evaluated and a slight decrease in adsorption capacity was observed after 4 cycles., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

The total amount of immunoglobulin E (IgE) in human serum is an important parameter in diagnosing allergies. To reduce the false diagnosis of allergies and better assist in therapy, clinical studies can be performed to obtain accurate and reliable measurements of IgE. A magnetic beads (MBs)-based ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for total IgE measurement and the diagnosis of food allergies in serum was developed in this study. First, IgE was extracted by MBs coupled with anti-IgE antibody from serum. The extracted IgE was quantified by a specific signal peptide after digestion. A spiked linear IgE concentration ranging from 400 to 5000 ng mL -1 was used for quantification. The limits of detection and quantification were 400 ng mL -1 and 800 ng mL -1 , respectively, for the developed method. Additionally, the combined capacity of the extracted IgE with different allergic proteins was evaluated by a binding experiment in vitro. The combining capacity of IgE with different allergens was used to speculate the kind of allergens that induce allergies in patients. Overall, a new method was developed that could be used to quantify the amount of IgE and simultaneously diagnose which allergen causes an allergic reaction, and this method may provide a powerful new tool in the clinical detection of allergies. Moreover, the developed method was applied to analyze IgE in four samples of patient serum and four serum samples from healthy individuals., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Aims: Diagnosis of fish may represent an important challenge for the allergists. This study aimed to evaluate the diagnostic sensitivity of an in vitro multiplex assay using a comprehensive panel of fish allergens and the cross-reactivity patterns between different molecular components., Methods: 56 subjects with fish allergy were enrolled. All patients underwent specific IgE measurement using the Allergy Explorer-Alex 2™ multiplex assay (Macroarray Diagnostics, Vienna, Austria) RESULTS: The single ß-parvalbumins Clu h 1, Cyp c 1, Gad m 1, Sal s 1, Sco s 1, Thu a 1 and Xyp g 1 scored positive in 75.0%, 67.8%, 62.5%, 80.3%,80.3%, 78.8% and 73,2% patients, respectively. 14.3% scored positive for the α-parvalbumin (Raj c-parvalbumin), and 16.1% for the aldolase + enolase (Gad m 2 + 3) components. 92.8% reacted to at least one ß-parvalbumin and 96.4% to at least one of the allergens tested. Overall sensitivity was higher than that obtained using commercial extracts of cod, salmon and tuna for skin prick test (75.8%) and IgE detection (92.3%)., Conclusions: The Alex 2 showed high diagnostic sensitivity and it might be used as an additional assay to investigate the cross-reactivity patterns between different molecular components, looking for potentially safe fish species., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To identify a brand, key messages and resources to underpin a public health approach to food allergy prevention., Methods: A focus group design was used to explore perceptions and opinions of potential brands, infant feeding messages and resources for providing standardised food allergy prevention information. Focus groups were conducted in February 2018 using interview guides and were transcribed verbatim. A content analysis of the transcripts was undertaken using thematic analysis software. The University of Western Australia provided ethics approval: RA/4/20/4280., Results: Seven focus groups with 39 participants were conducted. Four slogans and styles of imagery were considered. 'Nip Allergies in the Bub' was the most favoured slogan and images of babies with food were most favoured. Participant feedback was sought regarding messages and supporting messages were considered important. Participants were consulted about useful resources and a website was identified., Conclusions: Conducting focus groups assisted the selection of a brand, messages and resources to underpin a public health approach to implementing allergy prevention guidelines., Implications for Public Health: This is the first focus group research undertaken for food allergy prevention. Identification of a meaningful brand, key messages and resources will support a public health approach to implementing allergy prevention guidelines., (© 2022 The Authors.)

Background: We recently showed that seasonal patterns of COVID-19 incidence and Influenza-Like Illnesses incidence are highly similar, in a country in the temperate climate zone, such as the Netherlands. We hypothesize that in The Netherlands the same environmental factors and mobility trends that are associated with the seasonality of flu-like illnesses are predictors of COVID-19 seasonality as well., Methods: We used meteorological, pollen/hay fever and mobility data from the Netherlands. For the reproduction number of COVID-19 (R t ), we used daily estimates from the Dutch State Institute for Public Health. For all datasets, we selected the overlapping period of COVID-19 and the first allergy season: from February 17, 2020 till September 21, 2020 (n = 218). Backward stepwise multiple linear regression was used to develop an environmental prediction model of the R t of COVID-19. Next, we studied whether adding mobility trends to an environmental model improved the predictive power., Results: Through stepwise backward multiple linear regression four highly significant (p < 0.01) predictive factors are selected in our combined model: temperature, solar radiation, hay fever incidence, and mobility to indoor recreation locations. Our combined model explains 87.5% of the variance of R t of COVID-19 and has a good and highly significant fit: F(4, 213) = 374.2, p < 0.00001. This model had a better overall predictive performance than a solely environmental model, which explains 77.3% of the variance of R t (F(4, 213) = 181.3, p < 0.00001)., Conclusions: We conclude that the combined mobility and environmental model can adequately predict the seasonality of COVID-19 in a country with a temperate climate like the Netherlands. In this model higher solar radiation, higher temperature and hay fever are related to lower COVID-19 reproduction, and higher mobility to indoor recreation locations is related to an increased COVID-19 spread., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

We designed a SERS-based method to detect β-lactoglobulin (β-Lg), a major allergen of milk, utilizing aptamers to specifically anchor β-Lg. The Au-Ag nanourchins with excellent Raman enhancement effects were prepared and modified with a β-Lg aptamer as the capture substrate. By taking advantage of the hybridization of aptamer and Raman reporter molecule (6-Carboxyl-X-Rhodamine: ROX)-labeled complementary DNA (cDNA), when ROX is close to Au-Ag nanourchins, the SERS signal is enhanced. In the presence of β-Lg, aptamer binding to β-Lg induces the dissociation of ROX-cDNA from Au-Ag nanourchins, thereby decreasing the SERS signal. Under optimal conditions, the present bioassay provides a wide detection range of 10 ng/mL to 1000 ng/mL with a detection limit of 0.07 ng/mL. In addition, the established SERS sensor can selectively and accurately identify β-Lg with recovery rates of 93.25-107.0% in milk samples. It provides great potential as a sensitive and reliable detection method against the growing threat of allergens., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The peripheral nervous system and the immune system are virtually distributed in all organs in mouse and human. They act in concert to constitute an exceptional sensory system capable of sensing threatening stimuli, including allergens, and triggering appropriate biological responses. Recent advances in the field have revealed that tissue-resident mast cells and nearby sensory neurons could form functional neuroimmune clusters driven by bidirectional interactions and predisposed to significantly influence major allergic conditions. In this review, we highlight recent discoveries that paved the way toward a better understanding of how mast cells and sensory neurons can communicate to regulate basic features of allergic disorders in different organs., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In addition to providing individualized, specific, and ample nutritional compounds, donkey milk (DM) offers immunological modulation during health and disease. Recently, DM has attracted major interest in preparing infant formulas due to its similarity to human milk in terms of high protein and lactose content and low-fat concentration. The antimicrobial, anti-inflammation, antioxidant, and hypo-allergenicity properties of DM in human infants are well-documented. The purpose of this review is to summarize the knowledge of studies done in characterizing the composition of DM, including bioactive macronutrient levels influenced by the lactation status. The manufacture of DM-based food products and promising therapeutic applications in humans will also be discussed. The beneficial health effects of DM have been extensively studied as a valuable alternative source to breast milk. DM has proven to be a suitable nutrient to relieve milk-related allergies in human infants as opposed to cow's milk. Factors that influence the levels of macronutrients in DM include lactation status, processing, and manufacturing techniques. A wide variety of dairy products have been prepared using DM, such as cheese, ice cream, milk powder, novel functional fermented beverages, and milk powder for infant formulas. The bioactive macromolecules of DM exhibit antibacterial, antiviral, and antifungal effects as well as hypo-allergenicity, anti-inflammation, and antioxidant properties., (Copyright © 2022. Published by Elsevier Inc.)

The incidences of respiratory allergies are at an all-time high. Pollen aeroallergens can reflect changing climate, with recent studies in Europe showing some, but not all, pollen types are increasing in severity, season duration and experiencing an earlier onset. This study aimed to identify pollen trends in the UK over the last twenty-six years for a range of pollen sites, with a focus on the key pollen types of Poaceae (grass), Betula (birch) and Quercus (oak) and to examine the relationship of these trends with meteorological factors. Betula pollen seasons show no significant trends for onset, first high day or duration but increasing pollen production in the Midlands region of the UK is being driven by warmer temperatures in the previous June and July. Quercus pollen seasons are starting earlier, due to increasing temperature and sunshine totals in April, but are not becoming more severe. The seasons are lasting longer, although no significant climate drivers for this were identified. The first high day of the Poaceae pollen season is occurring earlier in central UK regions due to an increasing trend for all temperature variables in the previous December, January, April, May and June. Severity and duration of the season show no significant trends and are spatially and temporally variable. Important changes are occurring in the UK pollen seasons that will impact on the health of respiratory allergy sufferers, with more severe Betula pollen seasons and longer Quercus pollen seasons. Most of the changes identified were caused by climate drivers of increasing temperature and sunshine total. However, Poaceae pollen seasons are neither becoming more severe nor longer. The reasons for this included a lack of change in some monthly meteorological variables, or land-use change, such as grassland being replaced by urban areas or woodland., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background/objective: Urban greenspace may have a beneficial or adverse effect on respiratory health. Our objective was to perform an exploratory systematic review to synthesise the evidence and identify the potential causal pathways relating urban greenspace and respiratory health., Methods: We followed PRISMA guidelines on systematic reviews and searched five databases for eligible studies during 2000-2021. We incorporated a broad range of urban greenspace and respiratory health search terms, including both observational and experimental studies. Screening, data extraction, and risk of bias, assessed using the Navigation Guide criteria, were performed independently by two authors. We performed a narrative synthesis and discuss suggested pathways to respiratory health., Results: We identified 108 eligible papers (n = 104 observational, n = 4 experimental). The most common greenspace indicators were the overall greenery or vegetation (also known as greenness), green land use/land cover of physical area classes (e.g., parks, forests), and tree canopy cover. A wide range of respiratory health indicators were studied, with asthma prevalence being the most common. Two thirds (n = 195) of the associations in these studies were positive (i.e., beneficial) with health, with 31% (n = 91) statistically significant; only 9% (n = 25) of reported associations were negative (i.e., adverse) with health and statistically significant. The most consistent positive evidence was apparent for respiratory mortality. There were n = 35 (32%) 'probably low' and n = 73 (68%) 'probably high' overall ratings of bias. Hypothesised causal pathways for health benefits included lower air pollution, more physically active populations, and exposure to microbial diversity; suggested mechanisms with poorer health included exposure to pollen and other aeroallergens., Conclusion: Many studies showed positive association between urban greenspace and respiratory health, especially lower respiratory mortality; this is suggestive, but not conclusive, of causal effects. Results underscore the importance of contextual factors, greenspace metric employed, and the potential bias of subtle selection factors, which should be explored further., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Atopic dermatitis is a skin disorder caused by skin dryness and barrier dysfunction, resulting in skin inflammation and chronic itch (or pruritus). The pathogenesis of atopic dermatitis is thought to be initiated by a lowering of the itch threshold due to dry skin. This lowering of the itch threshold is at least partially due to the increase in intraepidermal nerve fibers and sensitization of sensory nerves by interleukin (IL)-33 produced and secreted by keratinocytes. Such skin is easily prone to itch due to mechanical stimuli, such as rubbing of clothing and chemical stimuli from itch mediators. In patients with atopic dermatitis, once itch occurs, further itch is induced by scratching, and the associated scratching breaks down the skin barrier. Disruption of the skin barrier allows entry into the epidermis of external foreign substances, such as allergens derived from house dust mites, leading to an increased induction of type 2 inflammatory responses. As a result, type 2 cytokines IL-4, IL-13, and IL-31 are mainly secreted by Th2 cells, and their action on sensory nerve fibers causes further itch sensitization. These sequences of events are thought to occur simultaneously in patients with atopic dermatitis, leading to a vicious itch-scratch cycle. This vicious cycle becomes a negative spiral that leads to disease burden. Therefore, controlling itch is essential for the treatment of atopic dermatitis. In this review, we summarize and discuss advances in the mechanisms of peripheral itch sensitization in atopic dermatitis, focusing on skin barrier-neuro-immune triadic connectivity., (Copyright © 2022 Japanese Society of Allergology. All rights reserved.)

Benefits for vitamin E intake in diseases with inflammatory components have been described and related in part, to endogenously formed metabolites (long-chain metabolites, LCM). Here, we have evaluated the role of LCM in relieving asthma features. To this aim, the endogenous vitamin E metabolite α-13'-carboxychromanol (α-T-13'-COOH) that acts as potent 5-lipoxygenase inhibitor has been administered either intraperitoneally or by oral gavage to BALB/c mice sensitized by subcutaneous injection of ovalbumin (OVA). We also have taken advantage of the metabolically stable α-T-13'-COOH derivative α-amplexichromanol (α-AC). Intraperitoneal treatment with α-T-13'-COOH reduced OVA-induced airway hyperreactivity (AHR) as well as peri-bronchial inflammatory cell infiltration. α-AC was more efficacious than α-T-13'-COOH, as demonstrated by better control of AHR and in reducing subepithelial. Both compounds exerted their protective function by reducing pulmonary leukotriene C 4 levels. Beneficial effects of α-AC were coupled to inhibition of the sensitization process, as indicated by a reduction of IgE plasma levels, lung mast cell infiltration and Th2 immune response. Metabololipidomics analysis revealed that α-AC raises the pulmonary levels of prostanoids, their degradation products, and 12/15-lipoxygenase metabolites. Following oral administration, the pharmacodynamically different profile in α-T-13'-COOH and α-AC was abrogated as demonstrated by a similar and improved efficacy in controlling asthma features as well as by metabololipidomics analysis. In conclusion, this study highlights a role for LCM and of vitamin E derivatives as pharmacologically active compounds that ameliorate asthmatic features and defines an important role for endogenous vitamin E metabolites in regulating immune response underlying the sensitization process., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The basophil activation test (BAT) has emerged as a reliable complementary diagnostic to document IgE-dependent allergies and to study cross-reactivity between structural homologues. However, the BAT has some weaknesses that hinder a wider application. The BAT requires fresh blood samples and is lost as a diagnostic in patients showing a non-responder status of their cells. The BAT is difficult to standardize mainly because of the difficulty to perform batch analyses. In contrast, mast cell activation tests (MATs), using passively sensitized mast cells (MCs) with patients' sera (henceforth indicated as passive MAT; pMAT), use serum samples that can be frozen, stored, and shipped to a reference center experienced in MC lines and/or cultures and capable of offering batch testing. With the recent recognition of the Mas-related G protein-coupled receptor X2 (MRGPRX2) occupation as a putative mechanism of immediate drug hypersensitivity reactions, the MAT has another advantage compared to the BAT. MCs, in contrast to resting basophils, express the MRGPRX2 and can therefore be used to study this IgE-independent mechanism. This review provides a status update of pMAT in the diagnosis of allergic IgE-mediated hypersensitivity and speculates how direct activation of MCs via the MRGPRX2 receptor could advance paradigms for this non-allergic hypersensitivity., (Copyright © 2022. Published by Elsevier B.V.)

Food allergy induced by lipid transfer proteins (LTPs) of Rosacea fruit family, such as peach, is becoming an important health problem in the Mediterranean area. Current treatments, such as allergen specific immunotherapy (AIT) with allergenic extracts show promising, but in many cases, they need an improvement in homogeneity, availability and induction of tolerant responses. Peptide-based vaccines containing adjuvants, such as carbohydrates for C-type lectin receptors (CLRs) are presented as an alternative approach. In this work, we have prepared fucosylated glycodendropeptides (GDPs) functionalized with Pru p 3 peptides via click chemistry. These GDPs, D n Fuc 9 Prup3, induced changes in moDC maturation and lymphocyte proliferation in food allergic patients, indicating specific recognition via DC-SIGN receptor. From these data, D 4 Fuc 9 Prup3 can be considered a promising candidate for specific immunotherapy development., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Allergen-specific immunoglobulins have a crucial role in allergic diseases. Most wheeze episodes develop before school age, and allergic rhinitis later develops during early elementary school years. However, the clinical background and cytokine/chemokine profiles associated with changes in immunoglobulins during early school-age are poorly understood., Methods: This study used blood samples from children participating in the JECS Pilot Study. We examined nineteen kinds of aeroallergen-specific immunoglobulins (IgE, IgG1, IgG4, and IgA) levels in patients at age 6 and age 8. Fluctuations of Der f 1- and Cry j 1-specific immunoglobulins levels during the two periods were compared to assess the frequency of allergic statuses and clusters of cytokine/chemokine profiles., Results: The medians of aeroallergen-specific IgE levels did not fluctuate, and almost all IgG1 and IgG4 decreased. In IgA, four (e.g., Der f 1) increased, whereas the other four (e.g., Cry j 1) decreased. The ratio of the Der f 1-specific IgG1 level at age 8 to that at age 6 was higher in children with poor asthma control than in children with better asthma control. Moreover, the cytokine/chemokine cluster with relatively lower IL-33 and higher CXCL7/NAP2 was associated with lower Der f 1- and Cry j 1-specific IgG4 levels, but not IgE levels., Conclusions: The cluster of cytokine/chemokine profiles characterized by lower IL-33 and higher CXCL7/NAP2 was associated with the maintenance of aeroallergen-specific IgG4 levels. This result provides a basis for considering the control of aeroallergen-specific immunoglobulins., (Copyright © 2022 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Abstract: Rapid hygiene monitoring tests based on the presence of ATP have been widely used in the food industry to ensure that adequate cleanliness is maintained. In this study, the practical applications and limitations of these tests and recent technological progress for facilitating more accurate control were evaluated. The presence of ATP on a surface indicates improper cleaning and the presence of contaminants, including organic debris and bacteria. Food residues are indicators of insufficient cleaning and are direct hazards because they may provide safe harbors for bacteria, provide sources of nutrients for bacterial growth, interfere with the antimicrobial activity of disinfectants, and support the formation of biofilms. Residues of allergenic foods on a surface may increase the risk of allergen cross-contact. However, ATP tests cannot detect bacteria or allergenic proteins directly. To ensure efficient use of commercially available ATP tests, in-depth knowledge is needed regarding their practical applications, methods for determining pass-fail limits, and differences in performance. Conventional ATP tests have limitations due to possible hydrolysis of ATP to ADP and AMP, which further hinders the identification of food residues. To overcome this problem, a total adenylate test was developed that could detect ATP+ADP+AMP (A3 test). The A3 test is suitable for the detection of adenylates from food residues and useful for verification of hygiene levels. The A3 test in conjunction with other methods, such as microorganism culture and food allergen tests, may be a useful strategy for identifying contamination sources and facilitating effective hygiene management., (Published 2022 by the International Association for Food Protection.)

The inclusion of undeclared cow's milk proteins may cause health complications to milk-allergic consumers and is one of the leading cause of food recall in many countries all over the world. Therefore, to keep control on such incidences in processed products, we established a milk sandwich ELISA test kit by incorporating two polyclonal antibodies against milk proteins obtained from different species. Its analytical effectiveness in terms of sensitivity, specificity, accuracy, trueness, and precision were all analyzed. The limit of detection (LOD) of the test kit was 0.011 ppm, with high specificity for milk protein residues. The test kit was highly specific, apart from considerable cross-reactivity with goat milk and minor cross-reactivity with donkey and horse milk. The coefficient of variation of the test kit for intra-assay ranged from 4.02% to 14.62% and inter-assay ranged from 6.05% to 15.08% respectively. The sandwich ELISA was highly specific in detecting commercial food products. In a limited retail survey, 5/6 of the milk proteins declared on the ingredient labels tested positive for milk proteins. The study offers effective technical support for the sensitive detection of milk products both for food manufacturers and regulatory authorities., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Atopic dermatitis (AD) is a chronic inflammatory skin disease; the three major factors responsible for AD, i.e., epidermal barrier dysfunction, allergic inflammation, and itching, interact with each other to form a pathological condition. Excessive protease activities are characteristic abnormalities that affect the epidermal barrier in patients with AD. In normal skin, epidermal serine protease activities are controlled by kallikrein-related peptidases (KLKs) and their inhibitors, including lympho-epithelial Kazal-type-related inhibitor (LEKTI). In AD lesions, KLKs are excessively expressed, which results in the enhancement of epidermal serine protease activities and facilitates the invasion by allergens and microorganisms. In addition, some KLKs can activate protease-activated receptor 2 (PAR2) in epidermal keratinocytes and peripheral nerves, resulting in the induction of inflammation and itching. Furthermore, in AD patients with single nucleotide polymorphism (SNP) such as E420K and D386N of SPINK5 which encodes LEKTI, LEKTI function is attenuated, resulting in the activation of KLKs and easy invasion by allergens and microorganisms. Further analysis is needed to elucidate the detailed mechanism underlying the control of serine protease activities, which may lead to the development of new therapeutic and prophylactic agents for AD., Competing Interests: Declaration of Competing Interest S. Morizane has received research support from Mitsubishi Tanabe Pharma Co., Sanofi K.K., and Maruho Co., Ltd., and honoraria for lectures from Eli Lilly Japan K.K., AbbVie GK, Pfizer Japan Inc., Torii Pharmaceutical Co.,Ltd, Sanofi K.K., and Maruho Co., Ltd. D. The remaining authors state no conflict of interest., (Copyright © 2022 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Background: We investigated whether multiple food allergies could be safely prevented by simultaneously administering very small amounts of multiple foods., Methods: Infants 3-4 months old with atopic dermatitis from 14 primary care pediatric clinics in Japan were enrolled in this randomized, placebo-controlled trial. The infants were administered either mixed allergenic food powder (MP) containing egg, milk, wheat, soybean, buckwheat, and peanuts, or placebo powder (PP). The amount of powder was increased in a stepwise manner on weeks 2 and 4, and continued until week 12. The occurrence of food allergy episodes after powder intervention was assessed at 18 months old. This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (number UMIN000027837)., Results: A total of 163 participants were randomly allocated to either the MP group (n = 83) or the PP group (n = 80). The incidence of food allergy episodes by 18 months was significantly different between the MP and PP groups (7/83 vs. 19/80, respectively; risk ratio 0.301 [95% CI 0.116-0.784]; P = 0.0066). Egg allergies were reduced in the MP group. In addition, food allergy episodes from any of the other five foods were significantly reduced, although the reductions in those due to individual foods were not significant., Conclusions: Gradually increasing the intake of very small amounts of multiple foods in early infancy can safely reduce the incidence of egg allergies. Other foods may also suppress food allergies, but no definitive conclusions could be reached., (Copyright © 2022 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Bronchial asthma (BA) is a heterogeneous chronic inflammatory disease of the airways. The majority of patients with mild to moderate BA develop Th2-biased eosinophilic pulmonary inflammation and respond well to corticosteroid treatment. However up to 10% of BA patients develop severe pathology, which is associated with neutrophilic inflammation and resistant to conventional corticosteroid therapy. Contrary to eosinophil-predominant airway inflammation neutrophilic BA is developed through Th1- and Th17-immune responses. However, the etiology of corticoid insensitive neutrophilic BA is still remains unclear. Therefore, in the current study we developed a mouse model of BA with predominant neutrophilic rather than eosinophilic pulmonary inflammation. BALB/c mice were immunized with the mixture of the ovalbumin allergen and Freund's adjuvant, followed by aerosol challenge with the same allergen mixed with E. coli lipopolysaccharide. As a result, mice developed the main BA manifestations: production of allergen specific IgE, development of airway hyperreactivity, airway remodeling and pulmonary neutrophilic inflammation. Moreover, this pathology developed through Th1- and Th17-dependent mechanisms and mice with induced neutrophilic BA phenotype responded poorly to dexamethasone treatment, that coincide to clinical observations. The established mouse model could be useful both for studying the pathogenesis and for testing novel approaches to control neutrophilic BA., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Respiratory tract infection early in life plays a significant role in the pathogenesis of asthma. In the present study we examine, using a murine surrogate, the effects of early life respiratory infection with Streptococcus pneumoniae (SP) on adult asthma induced by sensitisation and exposure to house dust mite (HDM) allergen. Mice (one week old) were infected with SP, then 3 weeks later sensitised to HDM emulsified with Al (OH)3 intraperitoneally and challenged intranasally with same allergen for up to a further 5 weeks to establish the asthma surrogate. Outcome measures were quantified using the FlexiVent apparatus, histology and immunohistology, ELISA and flow cytometry. The murine surrogates of asthma infected with SP early in life exhibited significantly more severe disease compared with the controls of mice without SP infection, as shown by airways responsiveness, inflammatory cellular infiltration of the airways, expression of markers of airways remodelling, serum concentrations of HDM-specific IgE and the concentrations of Th2-type cytokines and the numbers of activated Th2 and ILC2 cells in the lung tissues. These data are compatible with the hypothesis that early-life infection of the airways with SP exacerbates, at least in some individuals, subsequent HDM-induced allergic airways inflammation and associated asthma in adulthood in this murine surrogate., (Copyright © 2022. Published by Elsevier Inc.)

Mutated and unmutated IgE and IgG play different and partly opposing roles in allergy development, but the mechanisms controlling their relative production are incompletely understood. Here, we analyzed the IgE-response in murine food allergy. Deep sequencing of the complementary-determining region (CDR) repertoires indicated that an ongoing unmutated extrafollicular IgE response coexists with a germinal center response, even after long-lasting allergen challenges. Despite overall IgG1-dominance, a significant proportion of clonotypes contained several-fold more IgE than IgG1. Clonotypes with differential bias to either IgE or IgG1 showed distinct hypermutation and clonal expansion. Hypermutation rates were associated with different physiochemical binding properties of individual B-cell receptors (BCR). Increasing BCR signaling strength inhibited class switching from IgG1 to IgE in vitro, preferentially constraining IgE formation. These data indicate that antigen-binding properties of individual BCRs determine differential IgE hypermutation and IgE versus IgG1 production on the level of single B-cell clones., (© 2022. The Author(s).)

Background: Peptide-based immunotherapy (PIT) was introduced as an attractive approach in allergen-specific immunotherapy (AIT). However, PIT clinical trials have shown variable results, and immune response to peptides is not precisely predictable. On the other hand, induction of antigen-specific tolerance may be augmented when allergens are combined with the regulatory T cell epitope (Tregitope). This study aimed to evaluate the therapeutic administration of a plasmid DNA encoding Tregitope and ovalbumin (OVA) immunodominant epitope in the murine model of allergy., Methods: Following the induction of allergic rhinitis by ovalbumin, vaccinated group received three doses of recombinant plasmid containing Signal peptide-Tregitope-OVA T cell epitope. After the final OVA challenge, clinical symptoms, histopathological changes, OVA-specific IgE level, and cytokine secretion pattern of spleen cells were examined., Results: Our data are showing that AIT with the recombinant DNA vaccine significantly suppressed airway inflammation; reduced eosinophilic infiltration in the nasal mucosa; decreased expression level of IL-4 and IL-17 in spleen cells, while IFN-γ, IL-10, and TGF-β expression were increased. Moreover, OVA-specific IgE levels were also decreased., Conclusion: These results suggest that Tregitope-immunodominant T cell epitope fusion can act as a safe and effective approach in DNA-based allergen-specific immunotherapy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Immunological memory of innate immune cells, also termed "trained immunity", allows for cross-protection against distinct pathogens, but may also drive chronic inflammation. Recent studies have shown that memory responses associated with type 2 immunity do not solely rely on adaptive immune cells, such as T- and B cells, but also involve the innate immune system and epithelial cells. Memory responses have been described for monocytes, macrophages and airway epithelial cells of asthmatic patients as well as for macrophages and group 2 innate lymphoid cells (ILC2) from allergen-sensitized or helminth-infected mice. The metabolic and epigenetic mechanisms that mediate allergen- or helminth-induced reprogramming of innate immune cells are only beginning to be uncovered. Trained immunity has been implicated in helminth-driven immune regulation and allergen-specific immunotherapy, suggesting its exploitation in future therapies. Here, we discuss recent advances and key remaining questions regarding the mechanisms and functions of trained type 2 immunity in infection and inflammation., (© 2022. The Author(s).)

Immune responses that result in asthma exacerbation are associated with allergen or viral exposure. Identification of common immune factors will be beneficial for the development of uniformed targeted therapy. We employed a House Dust Mite (HDM) mouse model of asthma and challenged allergic HDM mice with allergens (HDM, cockroach extract (CRE)) or respiratory syncytial virus (RSV). Purified lung immune cells underwent high-dimensional single-cell RNA deep sequencing (scRNA-seq) to generate an RNA transcriptome. Gene silencing with siRNA was employed to confirm the efficacy of scRNA-seq analysis. scRNA-seq UMAP analysis portrayed an array of cell markers within individual immune clusters. SCENIC R analysis showed an increase in regulon number and activity in CD11b - DC cells. Analysis of conserved regulon factors further identified Creb5 as a shared regulon between the exacerbation groups. Creb5 siRNAs attenuated HDM, CRE or RSV-induced asthma exacerbation. scRNA-seq multidimensional analysis of immune clusters identified gene pathways that were conserved between the exacerbation groups. We propose that these analyses provide a strong framework that could be used to identify specific therapeutic targets in multifaceted pathologies., (© 2022. The Author(s).)

Barrier integrity is central to the maintenance of healthy immunological homeostasis. Impaired skin barrier function is linked with enhanced allergen sensitization and the development of diseases such as atopic dermatitis (AD), which can precede the development of other allergic disorders, for example, food allergies and asthma. Epidemiological evidence indicates that children suffering from allergies have lower levels of dietary fibre-derived short-chain fatty acids (SCFA). Using an experimental model of AD-like skin inflammation, we report that a fermentable fibre-rich diet alleviates systemic allergen sensitization and disease severity. The gut-skin axis underpins this phenomenon through SCFA production, particularly butyrate, which strengthens skin barrier function by altering mitochondrial metabolism of epidermal keratinocytes and the production of key structural components. Our results demonstrate that dietary fibre and SCFA improve epidermal barrier integrity, ultimately limiting early allergen sensitization and disease development.The Graphical Abstract was designed using Servier Medical Art images ( https://smart.servier.com )., (© 2022. The Author(s).)

Antibiotics, among the most used medications in children, affect gut microbiome communities and metabolic functions. These changes in microbiota structure can impact host immunity. We hypothesized that early-life microbiome alterations would lead to increased susceptibility to allergy and asthma. To test this, mouse pups between postnatal days 5-9 were orally exposed to water (control) or to therapeutic doses of azithromycin or amoxicillin. Later in life, these mice were sensitized and challenged with a model allergen, house dust mite (HDM), or saline. Mice with early-life azithromycin exposure that were challenged with HDM had increased IgE and IL-13 production by CD4 + T cells compared to unexposed mice; early-life amoxicillin exposure led to fewer abnormalities. To test that the microbiota contained the immunological cues to alter IgE and cytokine production after HDM challenge, germ-free mice were gavaged with fecal samples of the antibiotic-perturbed microbiota. Gavage of adult germ-free mice did not result in altered HDM responses, however, their offspring, which acquired the antibiotic-perturbed microbiota at birth showed elevated IgE levels and CD4 + cytokines in response to HDM, and altered airway reactivity. These studies indicate that early-life microbiota composition can heighten allergen-driven Th2/Th17 immune pathways and airway responses in an age-dependent manner., (© 2022. The Author(s), under exclusive licence to Society for Mucosal Immunology.)

Considering the important role of Der f 2 in house dust mites mediating allergic diseases and allergic adverse effects during allergen-specific immunotherapy (AIT), we intend to develop a candidate of desensitization vaccines against Der f 2 without allergenicity. According to the reported immunoglobulin E (IgE)-binding B and T cell epitopes of Der f 2, four candidates of desensitization vaccines against Der f 2 were developed. Recombinant wild-type Der f 2 (rWt-Der f 2) preserved conformational and linear IgE-binding B epitopes. rWt-Der f 2 linearized by reduction and alkylation reactions (rWt-Der f 2 (red/alk)) and recombinant modified-type Der f 2 (rMt-Der f 2) were developed via destroying conformational and linear IgE-binding B epitopes respectively. rMt-Der f 2 linearized by reduction and alkylation reactions (rMt-Der f 2 (red/alk)) was developed by destroying conformational and linear IgE-binding B epitopes. T cell epitopes of 4 candidates were preserved. The change of their IgE-binding activity was determined by enzyme linked immunosorbent assay (ELISA), western blot and inhibition ELISA. Compared with rWt-Der f 2, the IgE-binding activity of rWt-Der f 2 (red/alk), rMt-Der f 2 and rMt-Der f 2 (red/alk) all decreased, which was consistent with the result of western blot. The IgE-binding activity of rMt-Der f 2 and rMt-Der f 2 (red/alk) was not significantly different (P = 0.0863 > 0.05), which was comparable to that of their corresponding negative controls (P = 0.3488 and 0.4459, both > 0.05). The result of inhibition ELISA also showed that their IgE-binding activity decreased, and rMt-Der f 2 (red/alk) was the lowest. Conclusively, we developed the candidate of desensitization vaccines against Der f 2, rMt-Der f 2 or rMt-Der f 2 (red/alk), nearly without allergenicity, which would potentially prevent HDM allergic patients from allergic adverse effects caused by AIT., (Copyright © 2022. Published by Elsevier GmbH.)

The NADPH oxidase DUOX1 contributes to epithelial production of alarmins, including interleukin (IL)-33, in response to injurious triggers such as airborne protease allergens, and mediates development of mucus metaplasia and airway remodeling in chronic allergic airways diseases. DUOX1 is also expressed in non-epithelial lung cell types, including macrophages that play an important role in airway remodeling during chronic lung disease. We therefore conditionally deleted DUOX1 in either lung epithelial or monocyte/macrophage lineages to address its cell-specific actions in innate airway responses to acute airway challenge with house dust mite (HDM) allergen, and in chronic HDM-driven allergic airway inflammation. As expected, acute responses to airway challenge with HDM, as well as type 2 inflammation and related features of airway remodeling during chronic HDM-induced allergic inflammation, were largely driven by DUOX1 with the respiratory epithelium. However, in the context of chronic HDM-driven inflammation, DUOX1 deletion in macrophages also significantly impaired type 2 cytokine production and indices of mucus metaplasia. Further studies revealed a contribution of macrophage-intrinsic DUOX1 in macrophage recruitment upon chronic HDM challenge, as well as features of macrophage activation that impact on type 2 inflammation and remodeling., (© 2022. The Author(s), under exclusive licence to Society for Mucosal Immunology.)

Betula (birch) pollen is one of the most important causes of respiratory allergy in Northern and Central Europe. While birch trees are abundant in Central, Northern, and Eastern Europe, they are scarce in the Mediterranean territories, especially in the Iberian Peninsula (IP), where they grow only in the northern regions and as ornamental trees in urban areas. However, the airborne birch pollen patterns in Catalonia (Northeastern IP) show abrupt high concentrations in areas with usually low local influence. The intensity of the derived health problems can be increased by outbreaks due to long-range pollen transport. The present work evaluates the different potential contributions to Catalonia from the main source regions: Pyrenees, Cantabria, and the forests of France and Central Europe. To this end, we computed the Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) back trajectories of air masses associated with the main Betula pollen peaks occurring simultaneously over different Catalan monitoring stations, and we studied their provenance over a 15-year period. The Vielha aerobiological station on the northern slopes of the Central Pyrenees was used to identify the dates of the pollen season in the Pyrenean region. In order to better understand the role of the Pyrenees, which is the nearest of the four birch forested regions, we classified the pollen peaks in the other Catalan stations into three groups based on the relationship between the peak and the pollen season in the Pyrenees. Our analysis of back-trajectory residence time, combined with the associated pollen concentration, reveals that two principal routes other than the Pyrenean forest sustain the northerly fluxes that enter Catalonia and carry significant concentrations of Betula pollen. This study has also allowed quantifying the differentiated contributions of the potential source regions. In addition, the Weather Research Forecast (WRF) mesoscale model has been used to study three specific episodes. Both models, HYSPLIT and WRF, complement each other and have allowed for better understanding of the main mechanisms governing the entry of birch pollen to the region., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: the built environment in urban areas may have side effects on children's respiratory health, whilst less is known for adulthood., Aim: to assess the association between increasing exposure to grey spaces and allergic status in an adult general population sample., Methods: 2070 subjects (age range 15-84 yrs), living in Pisa/Cascina, Italy, were investigated in 1991-93 through a questionnaire on health status and risk factors, skin prick test (SPT), serum Immunoglobulins E (IgE), and serum antibodies to benzo(a)pyrene diol epoxide (BPDE)-DNA adducts. Land-cover exposure within a 1000 m buffer from each subject's home address was assessed through the CORINE Land Cover program (CLC 1990) within the FP7/HEALS project (2013-2018). Participants' residential addresses were geocoded and the proportion of surrounding grey spaces was calculated. Through logistic regression models, adjusting for potential confounding factors, the effect of a 10% increase in grey spaces exposure on allergic biomarkers/conditions was assessed; the relationship with serum antibodies to BPDE-DNA adducts positivity was also analyzed., Results: A 10% increase in grey spaces coverage was associated with a higher probability of having SPT positivity (OR 1.07, 95% CI 1.02-1.13), seasonal SPT positivity (OR 1.12, 1.05-1.19), polysensitization (OR 1.11, 1.04-1.19), allergic rhinitis (OR 1.10, 1.04-1.17), co-presence of SPT positivity and asthma/allergic rhinitis (OR 1.16, 1.08-1.25), asthma/allergic rhinitis (OR 1.06, 1.00-1.12), presence of serum antibodies to BPDE-DNA adducts positivity (OR 1.07, 1.01-1.14)., Conclusions: grey spaces have adverse effects on allergic status and are related to a biomarker of polycyclic aromatic hydrocarbons exposure in adulthood. Thus, they may be used as a proxy of urban environmental exposure., (Copyright © 2021. Published by Elsevier Inc.)

Background: The exacerbation of asthma and respiratory allergies has been associated with exposure to aeroallergens such as pollen. Within an urban area, tree cover, level of urbanization, atmospheric conditions, and the number of source plants can influence spatiotemporal variations in outdoor pollen concentrations., Objective: We analyze weekly pollen measurements made between March and October 2018 over 17 sites in Toronto, Canada. The main goals are: to estimate the concentration of different types of pollen across the season; estimate the association, if any, between pollen concentration and environmental variables, and provide a spatiotemporal surface of concentration of different types of pollen across the weeks in the studied period., Methods: We propose an extension of the land-use regression model to account for the temporal variation of pollen levels and the high number of measurements equal to zero. Inference is performed under the Bayesian framework, and uncertainty of predicted values is naturally obtained through the posterior predictive distribution., Results: Tree pollen was positively associated with commercial areas and tree cover, and negatively associated with grass cover. Both grass and weed pollen were positively associated with industrial areas and TC brightness and negatively associated with the northing coordinate. The total pollen was associated with a combination of these environmental factors. Predicted surfaces of pollen concentration are shown at some sampled weeks for all pollen types., Significance: The predicted surfaces obtained here can help future epidemiological studies to find possible associations between pollen levels and some health outcome like respiratory allergies at different locations within the study area., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Background: In tree nut (TN) allergy, singleplex tests showed the diagnostic utility of rAna o 3, rCor a 14/nCor a 9, and nJug r 1/nJug r 4 for cashew/pistachio, hazelnut, and walnut allergies, respectively. However, disadvantages of the tests include high costs and excessive blood sampling in multi-sensitized patients, and a limited number of components. We investigated the utility of a multiplex macroarray (i.e., the ALEX 2 test) in TN allergy., Methods: In 169 children, skin prick test, the component- and extract-specific IgEs of TNs were investigated for clinical reactivity and tolerance., Results: The predictors (AUC = 0.962-0.749) of clinical reactivity to cashew, pistachio, hazelnut, and walnut were rPis v 1/rAna o 3, rPis v 1/rAna o 3/nPis v 2/nPis v 3, rCor a 14/nCor a 11/nCor a 9, and nJug r 1/nJug r 2/nJug r 6/nJug r 4, respectively. More than 93% of the patients with clinical reactivity to pistachio/cashew, hazelnut and walnut had positivity of (≥0.3 kU A /L) rPis v 1/rAna o 3, rCor a 14 and nJug r 1/nJug r 2, respectively. The highest accuracies of clinical reactivity to culprit nut were obtained with combination of rPis v 1, sIgE and SPT positivities for cashew/pistachio, rPis v 1 ≥ 1.0 kU A /L for pistachio, rCor a 14 ≥ 1.0 kU A /L for hazelnut and combination of nJug r 1 and nJug r 2 positivities for walnut, respectively. Also, higher concentrations of rPis v 1 (≥15.0 kU A /L), rCor a 14 (≥5.0 kU A /L) and nJug r 1/nJug r 2 (≥15.0 kU A /L) had %100 specificity and PPV in predicting clinical reactivity to cashew, hazelnut and walnut, respectively., Conclusions: Multiplex macroarray test is useful and reliable in the diagnosis of TN allergy in children, confirms and expands existing knowledge, and can be used as a stand-alone tool in the bottom-up diagnostic approach., (Copyright © 2021 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: The interval between antigen ingestion may influence the safety of oral food challenge tests (OFCs), especially in patients with severe food allergies., Methods: This retrospective chart review of OFCs eliciting objective reactions to wheat, egg, and milk that were performed between April 2012 and January 2021 evaluated an equivalent number of low-dose OFCs performed at 30-, 40-, or 60-min intervals. To avoid the influence of the potential allergy severity of the patients, the prediction scores of all intervals were matched. We evaluated the total symptom score (TS), total ingested dose, and the proportions of severe reactions (TS ≥ 30) and adrenaline use., Results: We analyzed 945 OFCs (wheat, n = 186; egg, n = 561; milk, n = 198). The 60-min OFC had significantly lower TS than the 30- and 40-min OFC methods in wheat (p < 0.001 and p = 0.003, respectively), egg (p < 0.001 for both), and milk (p < 0.001 and p = 0.018, respectively). The total dose in the 60-min method was significantly lower than in the 30-min method (p < 0.001 for all). The proportion of severe reaction (TS ≥ 30) in the 60-min method was significantly lower than that in the 30-min method for the egg and milk OFCs (p = 0.001 and p < 0.001, respectively). There was no difference in the rates of adrenaline injection., Conclusions: The 60-min interval is safer than 30- or 40-min intervals in wheat, egg, and milk OFCs in patients with a low threshold dose for food allergy., (Copyright © 2021 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: IgE-mediated egg allergy is a common food allergy worldwide. Patients with egg allergy are known to easily achieve tolerance compared to other allergens such as nuts. Oral food challenge (OFC) is often performed on patients diagnosed with or suspected of having IgE-mediated food allergy, but whether hen's egg OFC is useful in IgE-dependent egg allergy patients to avoid complete elimination remains unknown., Methods: We identified articles in which OFCs were performed in Japanese patients diagnosed with or suspected of having IgE-mediated egg allergy. We evaluated whether the OFCs were useful to avoid the complete elimination of eggs by assessing the following: (1) the number of patients who could avoid complete elimination; (2) the number of patients who experienced serious adverse events (SAEs); or (3) adverse events (AEs); (4) improvement in quality of life (QOL); and (5) immunological changes., Results: Fifty-nine articles were selected in the study; all the references were case series or case studies in which OFC was compared to pre-challenge conditions. The overall negative ratio against egg OFC was 62.7%, but an additional 71.9% of OFC-positive patients could take eggs when expanded to partial elimination. Of the 4182 cases, 1146 showed AEs in the OFC, and two cases reached an SAE. Two reports showed an improvement in QOL and immunological changes, although the evidence was weak., Conclusions: OFCs against eggs may be useful to avoid complete elimination, but medical professionals should proceed with the test safely and carefully., (Copyright © 2021 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Poaceae pollen is highly allergenic, with a marked contribution to the pollen worldwide allergy prevalence. Pollen counts are defined by the species present in the considered area, although year-to-year oscillations may be triggered by different parameters, among which are weather conditions. Due to the predominant role of Poaceae pollen in the allergenicity in urban green areas, the aim of this study was the analysis of pollen trends and the influence of meteorology to forecast relevant variations in airborne pollen levels. The study was carried out during the 1993-2020 period in Ourense, in NW Iberian Peninsula. We used a volumetric Lanzoni VPPS 2000 trap for recording Poaceae airborne pollen grains, and meteorological daily data were obtained from the Galician Institute for Meteorology and Oceanography. The main indexes of the pollen season and their trends were calculated. A correlation analysis and 'C5.0 Decision Trees and Rule-Based Models' data mining algorithm were applied to determine the influence of meteorological conditions on pollen levels. We detected atmospheric Poaceae pollen during 139 days on average, mainly from April to August. The mean pollen grains amount recorded during the pollen season was 4608 pollen grains, with the pollen maximum peak of 276 pollen/m 3 on 27 June. We found no statistically significant trends and slight slopes for the seasonal indexes, similarly to previous Poaceae studies in the same region. The calculated C5.0 model offered defined results, indicating that the combination of mean temperature above 17.46 °C and sunlight exposure higher than 12.7 h is conductive to significantly high pollen levels. The obtained results make possible the identification of risk moments during the pollen season for the activation of protective measures for sensitized population to grass pollen., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Since novel nutrient sources with high protein content, such as yeast, fungi, bacteria, algae, and insects, are increasingly introduced in the consumer market, safety evaluation studies on their potentially allergenic proteins are required. A pipeline for in silico establishing the sequence-based homology between proteins of spirulina (Arthrospira platensis) and chlorella (Chlorella vulgaris) micro-algae and those included in the AllergenOnline (AO) database (AllergenOnline.org) is described. The extracted proteins were first identified through tryptic peptides analysis by reversed-phase liquid chromatography and high resolution/accuracy Fourier-transform tandem mass spectrometry (RPLC-ESI-FTMS/MS), followed by a quest on the UniProt database. The AO database was subsequently interrogated to assess sequence similarity between identified microalgal proteins and known allergens, based on criteria established by the World Health Organization (WHO) and Food and Agriculture Organization (FAO). A direct search for microalgal proteins already included in allergen databases was also performed using the Allergome database. Six proteins exhibiting a significant homology with food allergens were identified in spirulina extracts. Five of them, i.e., two thioredoxins (D4ZSU6, K1VP15), a superoxide dismutase (C3V3P3), a glyceraldehyde-3-phosphate dehydrogenase (K1W168), and a triosephosphate isomerase (D5A635), resulted from the search on AO. The sixth protein, C-phycocyanin beta subunit (P72508), was directly obtained after examining the Allergome database. Two proteins exhibiting significant sequence homology with food allergens were retrieved in chlorella extracts, viz. calmodulin (A0A2P6TFR8), which is related to troponin c (D7F1Q2), and fructose-bisphosphate aldolase (A0A2P6TDD0). Specific serum screenings based on immunochemical tests should be undertaken to confirm or rule out the allergenicity of the identified proteins., (Copyright © 2022 Elsevier B.V. All rights reserved.)