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Magda Ines Teixeira Abreu,1,* Adalberto Fernandes Santos,1– 3,* Jorge MR Gama,4 Salete Valente,1,5 Maria Jesus Valente,1,5 Henrique Pereira,6,7 Frederico Regateiro,2,8– 10 Bernardo Sousa-Pinto,11,12 Maria Teresa Ventura,13,14 Jean Bousquet,15– 17 Luis Taborda-Barata1,2,18,19 1Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal; 2CICS-UBI – Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal; 3Faculty of Medicine, Agostinho Neto University, Luanda, Angola; 4Center of Mathematics and Applications, Faculty of Sciences, University of Beira Interior, Covilhã, Portugal; 5Department of Pulmonology, Cova da Beira University Hospital Centre, Covilhã, Portugal; 6Psychology and Education Department, Faculty of Human and Social Sciences, University of Beira Interior, Covilhã, Portugal; 7The Research Center in Sports Sciences, Health Sciences and Human Development (CIDESD), University of Beira Interior, Covilhã, Portugal; 8Institute of Immunology, Faculty of Medicine of the University of Coimbra, Coimbra, Portugal; 9Centro de Neurociências e Biologia Celular, CIBB, University of Coimbra, Coimbra, Portugal; 10Allergy & Clinical Immunology Unit, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; 11MEDCIDS - Department of Community Medicine, Information and Health Decision Sciences, Faculty of Medicine, University of Porto, Porto, Portugal; 12CINTESIS - Center for Health Technology and Services Research, University of Porto, Porto, Portugal; 13Unit of Geriatric Immunoallergology, University of Bari Medical School, Bari, Italy; 14Institute of Science of Food Production, National Research Council (Ispa-Cnr), Bari, Italy; 15Institute of Allergology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; 16Allergology and Immunology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany; 17Department of Pulmonology, University Hospital Montpellier, Montpellier, France; 18UBIAir - Clinical & Experimental Lung Centre, UBIMedical, University of Beira Interior, Covilhã, Portugal; 19Department of Immunoallergology, Cova da Beira University Hospital Centre, Covilhã, Portugal*These authors contributed equally to this workCorrespondence: Luis Taborda-Barata, Faculty of Health Sciences, University of Beira Interior, Avenida Infante D, Covilhã, Henrique, 6200-506, Portugal, Tel +351 275329001, Fax +351 275329003, Email tabordabarata@fcsaude.ubi.ptPurpose: To analyse factors affecting the ability to use the digital asthma monitoring application Mask-Air® in old-age individuals living in inland Portugal.Patients and Methods: In this observational study, patients with medically confirmed asthma who agreed to participate were interviewed and subdivided into Non-users Group: those who could not use the application and Users Group: those who could. Sociodemographic and psychological data, comorbidities, and asthma status were compared between groups. Assessment of reasons for refusal was based on a 6-item questionnaire.Results: Among the 72 sequentially recruited patients (mean age±SD 73.26± 5.43 yrs; 61 women; 11 men), 44 (61.1%; mean age±SD 74.64± 5.68 yrs; 38 women; 6 men)) were included in Non-users Group and 28 (38.9%; mean age±SD 71.11± 4.26 yrs; 23 women; 5 men) in Users Group. Non-users Group patients were significantly older, had lower socioeconomic level, and more frequently had severe asthma (25% vs 3.6%; Odds ratio=0.08 (95% CI=0.01– 0.81; p=0.033)) and diabetes (32.6% vs 7.4%; Odds ratio=0.17 (95% CI=0.03– 0.80; p=0.025)) than Users Group. The main reasons for not using the App were “Lack of required hardware” (n=35) and “Digital illiteracy” (n=26), but lack of interest to use the App among those who had conditions to use it was uncommon.Conclusion: Most old-age asthmatics living in Beira Interior either lack a smartphone or digital skills, which are significant obstacles to implementing app-based monitoring studies.Plain Language Summary: This study was done to see whether it was possible to use a mobile phone application (App) to help old-age asthmatics living in inner Central Portugal better monitor and self-manage their disease.The researchers interviewed a group of 72 patients with proven asthma who agreed to participate in the study. This group was subdivided into two subgroups: Non-users Group (44 patients) included those who could not use the App because they did not have a smartphone; Users Group (28 patients) included those who had all the conditions to use the App. Patients were helped to download the App (called MASK-Air), were given a thorough explanation about it, and about how it should be used on a daily basis to monitor their asthma symptoms.The researchers found that patients in Non-users Group were significantly older, had worse socioeconomic conditions, and more often had severe asthma and diabetes. They also discovered that the main reasons for not using the App were lack of a smartphone and not knowing how to use a smartphone.These results show that lacking a smartphone and not knowing how to use digital tools are frequent situations in old-age asthmatics living in inner Central Portugal, and these may be obstacles for patients in monitoring their own asthma symptoms.Keywords: asthma, mHealth, digital literacy, disease monitoring, old-age

Rejane Mattar,1 Sergio Barbosa Marques,1 Anibal Ferreira dos Santos,1 Maria do Socorro Monteiro,1 Kiyoshi Iriya,2 Flair José Carrilho1 1Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, SP, Brazil; 2Department of Pathology, University of São Paulo School of Medicine, São Paulo, SP, Brazil Objective: To verify whether the variable number of tandem repeat (VNTR) polymorphism in the IL-1RN gene that encodes the interleukin (IL)-1 receptor antagonist (IL-1Ra) plays a role in the outcome of gastrointestinal diseases associated with Helicobacter pylori (H. pylori) infection. Methods: Patients with normal endoscopy (n = 71), inflammation of the upper gastrointestinal tract only (n = 196), gastric ulcer (n = 28), duodenal ulcer (n = 76), and gastric cancer (n = 19) were studied. H. pylori infection was diagnosed by the urease test, histological examination, and polymerase chain reaction. The IL-1 receptor antagonist gene (IL-1RN intron 2 VNTR) was analyzed by polymerase chain reaction. Gastritis was scored according to the updated Sydney system of classification. Results: H. pylori infection was an independent risk factor for mild (odds ratio [OR] = 5.53 [95% confidence interval [CI] = 2.63–11.64; P < 0.05]), moderate (OR = 83.93 [95% CI = 29.7–237.18; P < 0.05]) and marked (OR = 47.47 [95% CI = 5.39–418.05; P < 0.05]) gastritis. The carriage of IL-1RN*2/*2 had a significant protective effect of H. pylori infection (OR = 0.31 [95% CI = 0.17–0.57; P < 0.05]). H. pylori infection was identified as an independent risk of inflammation, duodenal ulcer, and gastric ulcer. The carriage of IL-1RN*2/*2 was an independent risk factor for gastric cancer (OR = 5.81 [95% CI = 1.06–31.98; P < 0.05]); nonetheless, the carriage of allele 2 (IL-1RN*2/*2 plus IL-1RN*L/*2) had an independent protective effect on duodenal ulcer (OR = 0.45 [95% CI = 0.22–0.91; P < 0.05]). Conclusions: Allele 2 of the VNTR IL-1RN polymorphism had a protective effect against duodenal ulcer and H. pylori infection; however, it increased the risk of gastric cancer. Keywords: Helicobacter pylori, IL-1RN polymorphism, gastric cancer, peptic ulcer

Background: Adult-type hypolactasia, the physiological decline of lactase some time after weaning, was previously associated with the LCT -13910C>T polymorphism worldwide except in Africa. Lactase non-persistence is the most common phenotype in humans, except in northwestern Europe with its long history of pastoralism and milking. We had previously shown association of LCT -13910C>T polymorphism with adult-type hypolactasia in Brazilians; thus, we assessed its frequency among different Brazilian ethnic groups.Methods: We investigated the ethnicity-related frequency of this polymorphism in 567 Brazilians [mean age, 42.1 +/- 16.8 years; 157 (27.7%) men]; 399 (70.4%) White, 50 (8.8%) Black, 65 (11.5%) Brown, and 53 (9.3%) Japanese-Brazilian. DNA was extracted from leukocytes; LCT -13910C>T polymorphism was analyzed by PCR-restriction fragment length polymorphism.Results: Prevalence of the CC genotype associated with hypolactasia was similar (57%) among White and Brown groups; however, prevalence was higher among Blacks (80%) and those of Japanese descent (100%). Only 2 (4%) Blacks had TT genotype, and 8 (16%) had the CT genotype. Assuming an association between CC genotype and hypolactasia, and CT and TT genotypes with lactase persistence, 356 (62.8%) individuals had hypolactasia and 211 (37.2%) had lactase persistence. The White and Brown groups had the same hypolactasia prevalence (approximately 57%); nevertheless, was 80% among Black individuals and 100% among Japanese-Brazilians (P < 0.01).Conclusion: The lactase persistence allele, LCT -13910T, was found in about 43% of both White and Brown and 20% of the Black Brazilians, but was absent among all Japanese Brazilians studied. [ABSTRACT FROM AUTHOR]

Allergic patients are characterized by complex and patient-specific IgE sensitization profiles to various allergens, which are accompanied by different phenotypes of allergic disease. Molecular allergy (MA) diagnosis establishes the patient's IgE reactivity profile at a molecular allergen level and has moved allergology into the "Precision Medicine" era. Molecular allergology started in the late 1980s with the isolation of the first allergen-encoding DNA sequences. Already in 2002, the first allergen microarrays were developed for the assessment of complex IgE sensitization patterns. Recombinant allergens are used for a precise definition of personal IgE reactivity profiles, identification of genuine IgE sensitization to allergen sources for refined prescription of allergen-specific immunotherapy and allergen avoidance diagnosis of co- versus cross-sensitization, epidemiological studies and prediction of symptoms, phenotypes, and development allergic disease. For example, molecular IgE sensitization patterns associated with more severe respiratory allergies, severe food allergy and allergy to honeybee or vespids are already established. The implementation of MA diagnosis into daily clinical practice requires continuous medical education, training of doctors in MA diagnosis and may be facilitated by clinical decision support systems such as diagnostic algorithms which may take advantage of artificial intelligence (AI)., (Copyright © 2025. Published by Elsevier Inc.)

Background: Aging associated with the passage of time causes alterations in subcutaneous tissues and the overall appearance of the skin that generate aesthetic unconformities in people. Within the wide range of available techniques on the market, radiofrequency (RF) diathermy has emerged as one of the most used non-invasive methods to combat them., Objective: This clinical trial aims to determine and quantify the effectiveness and safety of the high-frequency RF-based device Symmed (Termosalud Inc., Gijón, Spain) in cellulite appearance improvement and thigh remodeling treatments., Material and Methods: Eight sessions of Symmed were performed every 72/96 h in eight subjects' thighs. Safety and effectiveness of the device were evaluated before and after the treatments by digital photographs, body contours measurements, and ultrasound images of skin echogenicity and fat tissue thickness. Information regarding the satisfaction level of the participants was obtained throughout a customized questionnaire., Results: After the treatments, significant reductions of 3% in thighs circumferences (p < 0.05) and 20% in subcutaneous fat layer thickness (p < 0.01) were detected. Dermal echogenicity, used as an indicator of skin organization and collagen content, showed a significant 6% increase (p < 0.05). Before and after photographs revealed a general improvement in skin appearance. The results were complemented by a high satisfaction level (100%) and the absence of adverse events., Conclusion: Symmed RF therapy is a non-invasive, safe, effective, and well-tolerated procedure for the treatment of thighs cellulite appearance and body remodeling., (© 2025 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

This European Academy of Allergy and Clinical Immunology (EAACI) guideline provides recommendations for the management of IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Following the confirmation of IgE-mediated food allergy diagnosis, allergen avoidance and dietary advice (with support of a specialised dietitian, if possible) together with the provision of a written treatment plan, education on the recognition of allergic symptoms and prescription of medication including adrenaline using an auto-injector are essential. Patients with significant anxiety and requirement for coping strategies may benefit from support from a clinical psychologist. As immunomodulatory interventions, omalizumab is suggested for treatment of IgE-mediated food allergy in children from the age of 1 and adults; and oral allergen-specific immunotherapy is recommended for children and adolescents with peanut allergy and suggested for milk and egg allergies (generally after 4 years of age for milk and egg). Sublingual and epicutaneous immunotherapy are suggested for peanut allergy but are not yet available at the point of care. Future research into disease modifying treatments for IgE-mediated food allergy are highly needed, with standardised and patient-focused protocols and outcomes., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

A substantial body of literature links attachment to childhood obesity. However, research on the mechanisms underlying this association is scarce. The present study aimed to test four serial indirect path models to examine whether caregivers' insecure attachment is related to children's food consumption, through its influence on emotional and feeding responsiveness. A total of 352 caregivers of preschool children reported on their attachment orientation, emotional responses to their children's distress, feeding practices, and their children's food consumption. Results showed that caregivers with higher levels of attachment avoidance and anxiety were more likely to use unsupportive emotional responses to children's distress, which predicted the increased use of unresponsive feeding practices, and consequently children's higher sugary and fatty/salty food consumption. Higher levels of attachment avoidance were also associated with children's lower fruit and vegetable consumption through lower use of supportive emotional responses and responsive feeding practices, while higher levels of attachment anxiety were associated with children's lower fruit and vegetable consumption only by lower use of responsive feeding practices. These findings suggest that the influence of insecure attachment on caregivers' emotion regulation may contribute to the use of specific feeding practices that, in turn, affect children's food intake and may have implications for obesity risk., 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 © 2024. Published by Elsevier Ltd.)

Food allergy is increasing in prevalence, and poses significant challenges for individuals and their families, adversely impacting their quality of life. Misdiagnosis can lead to unnecessary dietary and social limitations, and increased food allergy risk, while failure to diagnose may result in life-threatening anaphylaxis. Therefore, a precise diagnosis is of the utmost importance; however, barriers exist at every stage of the diagnostic process. Food allergy diagnosis relies on clinical history, IgE sensitization tests, and oral food challenges. Component testing and identification of optimal cut-offs have improved diagnostic accuracy. Nevertheless, many patients still require oral food challenges and better tests are needed to reduce this. Novel biomarkers, such as the basophil activation test and peptide IgE testing, are transitioning into clinical practice. Future approaches may include alternative biological samples, novel laboratory technologies, and analytical tools, including artificial intelligence, to integrate test results and clinical information. Conscientious use of existing tests, access to tests with superior diagnostic accuracy and combination of tests, can lead to improved precision of food allergy diagnosis and timely introduction of tolerated foods in the diet. This review summarizes recent advances in novel approaches for food allergy diagnosis that can enhance clinical decision-making, now and in the future., (Copyright © 2024. Published by Elsevier Inc.)

Mast cell tumours (MCTs) are the most frequent cutaneous neoplasia of the dog, and they have very variable biological behaviour and survival times. Surgery is still the best treatment, and despite the several adjuvant therapies described, many cases are very aggressive and resistant to these treatments making it urgent to find new therapeutic targets. Nowadays, immunotherapy targeting immune checkpoints has been described as a complementary treatment for several human cancers, but it is still very scarcely studied in veterinary medicine. Therefore, this study aimed to investigate the expression of the checkpoint proteins programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) to evaluate their potential as therapeutic targets for MCT. Through immunohistochemical study, it was analysed the expression of PD-L1 and CTLA-4 in 74 MCT cases from the archive of the Veterinary Pathology Laboratory of the University of Porto (LabPatVet). Tumour size, histological grade, ki-67 proliferation index, mitotic count and presence of metastatic disease were also assessed. Most of the cases expressed both immune checkpoints in neoplastic cells. There was a statistically significant inverse association between the expression of CTLA-4 and MCT grade (p < 0,001) and mitotic count (p < 0.001). PD-L1 was significantly and negatively related to HG (p = 0.004), and tumour size (р = 0.014). Tumour size, histological grade and mitotic count were positively associated with metastatic disease. Additionally, it was observed that the expression of PD-L1 and CTLA-4 was interrelated (p < 0.001). This study demonstrated that MCT cells express both PD-L1 and CTLA-4 and that their expression was associated with MCT prognostic factors., (© 2024 John Wiley & Sons Ltd.)

Selenocysteine (Sec) metabolism is crucial for cellular function and ferroptosis prevention and begins with the uptake of the Sec carrier, selenoprotein P (SELENOP). Following uptake, Sec released from SELENOP is metabolized via selenocysteine lyase (SCLY), producing selenide, a substrate for selenophosphate synthetase 2 (SEPHS2), which provides the essential selenium donor, selenophosphate (H 2 SePO 3 - ), for the biosynthesis of the Sec-tRNA. Here, we discovered an alternative pathway in Sec metabolism mediated by peroxiredoxin 6 (PRDX6), independent of SCLY. Mechanistically, we demonstrate that PRDX6 can readily react with selenide and interact with SEPHS2, potentially acting as a selenium delivery system. Moreover, we demonstrate the functional significance of this alternative route in human cancer cells, revealing a notable association between elevated expression of PRDX6 and human MYCN-amplified neuroblastoma subtype. Our study sheds light on a previously unrecognized aspect of Sec metabolism and its implications in ferroptosis, offering further possibilities for therapeutic exploitation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Immunoglobulin E (IgE)-mediated food allergies are reported to affect around 3.5% of children and 2.4% of adults, with symptoms varying in range and severity. While being the gold standard for diagnosis, oral food challenges are burdensome, and diagnostic tools based on specific IgE can be flawed. Furthering our understanding of the mechanisms behind food allergy onset, severity and persistence could help reveal immune profiles associated with the disease, to ultimately aid in diagnosis. Alterations to cytokine levels and immune cell ratios have been identified, though further research is needed to fully capture the heterogenous nature of food allergy. Moreover, the existence of such immune alterations also raises the question of potential wider systemic effects. For example, recent research has emphasised the existence and impact of neuro-immune interactions and implicated behavioural and neurological changes associated with food allergy. This review will provide an overview of such food allergy-driven neuro-immune interactions, with the aim of emphasising the importance of furthering our understanding of the immune mechanisms underlying IgE-mediated food allergy., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide. It attributes their onset to a functionally impaired epithelial barrier triggered by the toxicity of the exposed substances, associated with microbial dysbiosis, immune system activation, and inflammation. Diseases encompassed by the epithelial barrier theory share common features such as an increased prevalence after the 1960s or 2000s that cannot (solely) be accounted for by the emergence of improved diagnostic methods. Other common traits include epithelial barrier defects, microbial dysbiosis with loss of commensals and colonization of opportunistic pathogens, and circulating inflammatory cells and cytokines. In addition, practically unrelated diseases that fulfill these criteria have started to emerge as multimorbidities during the last decades. Here, we provide a comprehensive overview of diseases encompassed by the epithelial barrier theory and discuss evidence and similarities for their epidemiology, genetic susceptibility, epithelial barrier dysfunction, microbial dysbiosis, and tissue inflammation., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Food allergy represents an increasing global health issue, significantly impacting society on a personal and on a systems-wide level. The gold standard for diagnosing food allergy, the oral food challenge, is time-consuming, expensive, and carries risks of allergic reactions, with unpredictable severity. There is, therefore, an urgent need for more accurate, scalable, predictive diagnostic techniques. In this review, we discuss possible future directions in the world of food allergy diagnosis. We start by describing the current clinical approach to food allergy diagnosis, highlighting novel diagnostic methods recommended for use in clinical practice, such as the basophil activation test and molecular allergology, and go on to discuss tests that require more research before they can be applied to routine clinical use, including the mast cell activation test and bead-based epitope assay. Finally, we consider exploratory approaches, such as IgE glycosylation, IgG4, T and B cell assays, microbiome analysis, and plasma cytokines. Artificial intelligence is assessed for potential integrated interpretation of panels of diagnostic tests. Overall, a framework is proposed suggesting how combining established and emerging technologies can effectively enhance the accuracy of food allergy diagnosis in the future., Competing Interests: AS reports grants from Medical Research Council (MR/M008517/1; MC/PC/18052; MR/T032081/1), Food Allergy Research and Education (FARE), the Immune Tolerance Network/National Institute of Allergy and Infectious Diseases (NIAID, NIH), Asthma UK (AUK-BC-2015-01), BBSRC, Rosetrees Trust and the NIHR through the Biomedical Research Centre (BRC) award to Guy's and St Thomas' NHS Foundation Trust, during the conduct of the study; personal fees from Thermo Scientific, Nestle, Nutricia, Infomed, Novartis, Allergy Therapeutics, IgGenix, Buhlmann, as well as research support from IgGenix, Buhlmann and Thermo Fisher Scientific through a collaboration agreement with King's College London. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Wong and Santos.)

Background: Existing therapeutic strategies are challenged by long times to achieve effect and often require frequent administration. Peanut-allergic individuals would benefit from a therapeutic that provides rapid protection against accidental exposure within days of administration while carrying little risk of adverse reactions., Objective: Guided by the repertoire of human IgE mAbs from allergic individuals, we sought to develop a treatment approach leveraging the known protective effects of allergen-specific IgG4 antibodies., Methods: We applied our single-cell RNA-sequencing SEQ SIFTER platform (IgGenix, Inc, South San Francisco, Calif) to whole blood samples from peanut-allergic individuals to discover IgE mAbs. These were then class-switched by replacing the IgE constant region with IgG4 while retaining the allergen-specific variable regions. In vitro mast cell activation tests, basophil activation tests, ELISAs, and an in vivo peanut allergy mouse model were used to evaluate the specificity, affinity, and activity of these recombinant IgG4 mAbs., Results: We determined that human peanut-specific IgE mAbs predominantly target immunodominant epitopes on Ara h 2 and Ara h 6 and that recombinant IgG4 mAbs effectively block these epitopes. IGNX001, a mixture of 2 such high-affinity IgG4 mAbs, provided robust protection against peanut-mediated mast cell activation in vitro as well as against anaphylaxis upon intragastric peanut challenge in a peanut allergy mouse model., Conclusions: We developed a peanut-specific IgG4 antibody therapeutic with convincing preclinical efficacy starting from a large repertoire of human IgE mAbs from demographically and geographically diverse individuals. These results warrant further clinical investigation of IGNX001 and underscore the opportunity for the application of this therapeutic development strategy in other food and environmental allergies., Competing Interests: Disclosure statement The study was supported by IgGenix. A.F.S. acknowledges grants from the Medical Research Council (grant nos. MR/M008517/1, MC/PC/18052, and MR/T032081/1), Food Allergy Research and Education, the Immune Tolerance Network/National Institute of Allergy and Infectious Diseases, Asthma UK (grant no. AUK-BC-2015-01), Biotechnology and Biological Sciences Research Council (BBSRC), Rosetrees Trust, and the National Institute for Health and Care Research (NIHR) through the Biomedical Research Centre award to Guy’s and St Thomas’ National Health Service Foundation Trust during the conduct of the study. Disclosure of potential conflict of interest: D. Croote, J. J. W. Wong, P. Creeks, V. Aruva, R. Ferrini, G. R. Thomas, and H. B. Lowman are employees of, and/or stakeholders in, IgGenix. Patent applications assigned to IgGenix have been filed covering aspects of this work. R. G. Hamilton is a consultant for IgGenix. A. F. Santos received personal fees from Thermo Fisher Scientific, Novartis, Allergy Therapeutics, Nestle, and IgGenix; and received research support from IgGenix and Thermo Fisher Scientific through collaboration agreements with King’s College London. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: The basophil activation test (BAT) has shown evidence of high sensitivity and high specificity to support the diagnosis of IgE-mediated allergy. It is a functional test that uses live cells analyzed by flow cytometry and thus needs to be performed within 24h of blood collection. BAT has shown to be reproducible and reliable when tested in a clinical diagnostic laboratory with standardized protocols and flow cytometry settings., Areas Covered: In this review, we summarize the evidence to support clinical use of BAT and the next steps required for clinical implementation for an improve clinical care for patients with suspected IgE-mediated food allergy., Expert Opinion: BAT has recently been included in Clinical Guidelines of Food Allergy Diagnosis and its implementation in clinical practice depends largely on availability. Proposed clinical applications of the BAT include: distinction between food allergy and asymptomatic IgE sensitization; determination of food allergic status to peanut, tree nuts and seeds in polysensitized children; evaluation of tolerance to baked egg and baked milk in egg and milk allergic children; identification of patients at high-risk of severe allergic reactions; monitoring for spontaneous resolution of food allergy; confirmation of eligibility for specific treatments of food allergy; prediction and monitoring of response to immunomodulatory treatments.

Competing Interests: Disclosure and competing interests statement The authors declare no competing interests.

Purpose of Review: Recognition of the importance of innate lymphoid cells (ILCs) in the immune mechanisms of food allergy has grown in recent years. This review summarizes recent findings of ILCs in immunoglobulin E (IgE)-mediated food allergy. New research on ILCs in the context of the microbiome and other atopic diseases are also considered with respect to how they can inform understanding of the role of ILCs in food allergy., Recent Findings: ILCs can mediate allergic and tolerogenic responses through multiple pathways. A novel subset of interleukin (IL)-10 producing ILC2s are associated with tolerance following immunotherapy to grass pollen, house dust mite allergy and lipid transfer protein allergy. ILC2s can drive food allergen-specific T cell responses in an antigen-specific manner. A memory subset of ILC2s has been identified through studies of other atopic diseases and is associated with effectiveness of response to therapy., Summary: The role of ILCs in food allergy and oral tolerance is relatively understudied compared to other diseases. ILCs can modulate immune responses through several mechanisms, and it is likely that these are of importance in the context of food allergy. Better understanding of theses pathways may help to answer fundamental questions regarding the development of food allergy and lead to novel therapeutic targets and treatment., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Food allergy (FA) is associated with poor health-related quality of life and high levels of psychological distress. Psychological support is extremely important but not always available. As part of the Global Access to Psychological Services for Food Allergy (GAPS) study, we aimed to assess psychological distress and service use among adults, caregivers and children with FA in a global survey., Methods: Participants (n = 1329 adults with FA; n = 1907 caregivers of children with FA) from >20 countries were recruited through patient organisations, social media advertisements and online survey panels to complete an online survey. Surveys were available in six languages., Results: A total of 67.7% of adults and 77.2% of caregivers reported direct experience, and 51.6% of caregivers said their child had experienced FA-related psychological distress. The most commonly reported issue was anxiety about having an allergic reaction. Less than 20% had been assessed for FA-related psychological distress. There were significant differences across countries for levels of distress, screening for distress, seeing a mental health professional and being diagnosed with a FA-related mental health disorder (all p < .001). The United Kingdom, Australia and Brazil had the highest number of participants reporting distress. The most commonly reported barrier to seeing a mental health professional was cost., Conclusions: FA-related distress is common across countries, but with substantial country-to-country variability. Allergy providers are encouraged to routinely assess families for psychological distress and provide access to appropriate mental health resources. Development and implementation of evidence-based, patient-informed accessible, affordable FA interventions in multiple languages is urgently needed., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Excess body adiposity and skin irregularities represent a major problem in today's society. Currently, radiofrequency-based devices constitute an increasingly popular medical-aesthetic application and a powerful non-invasive method to combat this problem., Objective: This study aims to determine the efficacy and safety of the high-frequency device Zionic™ (Termosalud, Inc., Gijón, Spain) in reducing body contouring and improving skin appearance in the abdomen/flanks or thighs., Materials and Methods: Thirty nine individuals were treated with the Zionic™ device in the abdomen/flanks or thighs. A total of 8 sessions of 40-50 min each, 72/96 h apart were performed. At baseline, body measurements were taken including photographs, body contours, and ultrasound scans to assess dermal thickness, dermal echogenicity, and subcutaneous fat thickness. The measurements were repeated after the eight sessions for comparison and analysis. Quantitative data was complemented with a customized survey to evaluate participants satisfaction level., Results: At the follow-up visit, a significant average reduction of 3% in abdomen/flanks circumferences and 2% in thighs contours was noticed. Abdomen/flanks and thighs subcutaneous fat layer thickness was significantly reduced by 8% and 6%, respectively. Dermal echogenicity changes, related to skin collagen content and organization, showed non-significant increasing tendencies of 7% for abdomen/flanks and 8% for thighs. Thighs dermal thickness was significantly increased by 6%. Results were associated to a high satisfaction level (80%) and no severe adverse events., Conclusion: Zionic™ treatment is a safe, effective, and well-tolerated noninvasive procedure for body contouring and improvement of skin properties in abdomen, flanks, and thighs., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Various biomarkers are used to define peanut allergy (PA). We aimed to observe changes in PA resolution and persistence over time comparing biomarkers in PA and peanut sensitised but tolerant (PS) children in a population-based cohort., Methods: Participants were recruited from the EAT and EAT-On studies, conducted across England and Wales, and were exclusively breastfeed babies recruited at 3 months old and followed up until 7-12 years old. Clinical characteristics, skin prick test (SPT), sIgE to peanut and peanut components and mast cell activation tests (MAT) were assessed at 12 months, 36 months and 7-12 years. PA status was determined at the 7-12 year time point., Results: The prevalence of PA was 2.1% at 7-12 years. Between 3 and 7-12 year, two children developed PA and one outgrew PA. PA children had larger SPT, higher peanut-sIgE, Ara h 2-sIgE and MAT (all p < .001) compared to PS children from 12 months onwards. SPT, peanut-sIgE, Ara h 2-sIgE and MAT between children with persistent PA, new PA, outgrown PA and PS were statistically significant from 12 months onwards (p < .001). Those with persistent PA had SPT, peanut-sIgE and Ara h 2-sIgE that increased over time and MAT which was highest at 36 months. New PA children had increased SPT and peanut-sIgE from 36 months to 7-12 years, but MAT remained low. PS children had low biomarkers across time., Conclusions: In this cohort, few children outgrow or develop new PA between 36 months and 7-12 years. Children with persistent PA have raised SPT, peanut-sIgE, Ara h 2-sIgE and MAT evident from infancy that consistently increase over time., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

The aim of this study was to investigate whether simultaneous irradiation at 660 and 808 nm generates different patterns of oxidative/antioxidative activities compared to consecutive irradiation. Primary cultures of gingival keratinocytes and fibroblasts were exposed to a diose laser (660 ± 2 nm and 808 ± 2 nm, 100 mW, 0.09 cm 2 spot area) using double irradiation with the two wavelengths (consecutive or simultaneous) for 6, 10, and 20 s. The two irradiation regimens did not increase cell viability in any of the experimental conditions. Lipid peroxidation was increased after consecutive irradiation in epithelial cells, which was not detected after simultaneous irradiation. After 20s of the simultaneous mode, ROS levels increased, but antioxidative balance decreased. In the fibroblasts, the two double irradiations induced ROS reduction, increase in lipid peroxidation, and improvement of antioxidative balance, mainly after the 20 s irradiation time. In conclusion, simultaneous and consecutive irradiation induced distinct oxidative stress modulation in oral epithelial cells and fibroblasts. The imbalance in the oxidative system observed after longer exposures, allied with the absence of a significant increase in the viability of the two cell types, suggests a contraindication for longer simultaneous irradiation in clinical situations that demand cellular stimulation., (© 2023 The American Society for Photobiology.)

Objective: Digital interventions such as remote monitoring of symptoms and physiological measurements have the potential to reduce the economic burden of asthma and chronic obstructive pulmonary disease (COPD) but their cost-effectiveness remains unclear. This systematic review of randomised controlled trials (RCT) aims to assess whether digital health interventions can be cost-effective in these patients., Design: Systematic review of RCTs. Study quality was assessed using RoB2 tool., Data Sources: Systematic search in three databases: PubMed, Scopus and Web of Science., Eligibility Criteria: Studies were eligible if they were RCTs with health economic evaluations assessing participants with asthma and/or COPD and comparing a digital health intervention to standard of care., Results: We included 35 RCTs, of which 21 were related to COPD, 13 to asthma and one to both diseases. Overall, studies assessed four categories of digital health interventions: (i) Electronic patient diaries (n = 4), (ii) real-time monitoring (n = 19), (iii) teleconsultations (n = 6) and (iv) others (n = 6). Eleven studies performed a full economic evaluation analysis, while 24 studies performed a partial economic analysis. Most studies involving real-time monitoring or teleconsultations presented economic results in favour of digital health interventions (indicating them to be cost-effective or less expensive than the standard of care). Mixed results were obtained for electronic patient diaries. In the studies that conducted a full economic analysis, the incremental cost-effectiveness ratio (ICER) ranged from 3530,93€/QALY and 286,369,28€/QALY. In the studies that conducted a partial economic analysis, the cost differences between the intervention group and the control group ranged from 0,12€ and 85,217,86€. Half studies with low risk of bias concluded that the intervention was economically favourable., Conclusion: Although costs varied based on intervention type, follow-up period and country, most studies report digital health interventions to be affordable or associated with decreased costs., Trial Registration: PROSPERO: CRD42023439195., (© 2024 John Wiley & Sons Ltd.)

Derived from the myeloid lineage, granulocytes, including basophils, eosinophils, and neutrophils, along with mast cells, play important, often disparate, roles across the allergic disease spectrum. While these cells and their mediators are commonly associated with allergic inflammation, they also exhibit several functions either promoting or restricting tumor growth. In this Position Paper we discuss common granulocyte and mast cell features relating to immunomodulatory functions in allergy and in cancer. We highlight key mechanisms which may inform cancer treatment and propose pertinent areas for future research. We suggest areas where understanding the communication between granulocytes, mast cells, and the tumor microenvironment, will be crucial for identifying immune mechanisms that may be harnessed to counteract tumor development. For example, a comprehensive understanding of allergic and immune factors driving distinct neutrophil states and those mechanisms that link mast cells with immunotherapy resistance, might enable targeted manipulation of specific subpopulations, leading to precision immunotherapy in cancer. We recommend specific areas of investigation in AllergoOncology and knowledge exchange across disease contexts to uncover pertinent reciprocal functions in allergy and cancer and allow therapeutic manipulation of these powerful cell populations. These will help address the unmet needs in stratifying and managing patients with allergic diseases and cancer., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Food allergy (FA) is a potentially life-threatening chronic condition that is becoming an increasing public health problem worldwide. This systematic review (SR) was carried out to inform the development of clinical recommendations on the treatment of IgE-mediated FA with biologics and/or IT for the update of the EAACI guidelines. A SR of randomized-controlled trials or quasi-controlled trials was carried out. Studies were identified via comprehensive search strategies in Medline, Embase, and Cochrane Library, up to April 2022., Population: Human adults, children, and adolescents with IgE-mediated FA., Intervention: IT and/or biologics., Comparator: Placebo or standard-of-care (allergen avoidance)., Outcome: Efficacy (desensitization, sustained unresponsiveness (SU), remission), quality of life, and safety (systemic and local adverse reactions (AR)). The Cochrane RoB tool was used to assess the risk of bias. It was reported according to PRISMA and registered in PROSPERO CRD4202229828. After screening, 121 studies were included (111 for IT and 10 for biologics). Most studies had a high risk of bias and showed high heterogeneity in design and results. Metanalysis showed a positive effect of biologics and IT in terms of relative risk (RR) for achieving tolerance to the culprit food compared to avoidance or placebo. Omalizumab for any FA showed a RR of 2.17 [95% confidence interval: 1.22, 3.85]. For peanut allergy, oral IT (OIT) had a RR of 11.94 [1.76, 80.84] versus avoidance or placebo, sublingual IT (SLIT) had a RR of 3.00 [1.04, 8.66], and epicutaneous IT (EPIT) of 2.16 [1.56, 3.00]. OIT had a RR of 5.88 [2.27, 15.18] for cow's milk allergy, and of 3.43 [2.24, 5.27] for egg allergy. There was insufficient data on SLIT or EPIT for the treatment of egg and milk allergies. Most ARs reported were mild. For OIT the most common AR involved the gastrointestinal system and for EPIT, AR's most commonly affected the skin. There was limited data on severe or life-threatening ARs. There was limited evidence for long term efficacy and quality of life. In conclusion, biologics and IT, alone or in combination, are effective in achieving desensitization while on active treatment but more evidence is needed on long-term tolerance as current evidence is not of high quality. Adverse events while on therapy are generally mild to moderate but a long-term comprehensive safety profile is missing. There is a critical need to optimize and standardize desensitization protocols and outcome measures to facilitate our understanding of the efficacy and safety as well as to allow for comparison between interventions., (© 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Allergist-immunologists use serologic peanut allergy testing to maximize test sensitivity and specificity while minimizing cost and inconvenience. Recent advances toward this goal include a better understanding of specific IgE (sIgE) and component testing, epitope-sIgE assays, and basophil activation testing. Predicting reaction severity with serologic testing is challenged by a range of co-factors that influence reaction severity, such as the amount and form of any allergen consumed and comorbid disease. In 2020, the Allergy Immunology Joint Task Force on Practice Parameters recommended Ara h 2-sIgE as the most cost-effective diagnostic test for peanut allergy because of its superior performance, when compared with skin prick testing and serum IgE. Basophil activation testing, a functional test of allergic response not evaluated in the Joint Task Force on Practice Parameters guideline, is a promising option for both allergy diagnosis and prognosis. Similarly, epitope-sIgE testing may improve prediction of reaction thresholds, but further validation is needed. Despite advances in food allergy testing, many of these tools remain limited by cost, accessibility, and feasibility. In addition, there is a need for further research on how atopic dermatitis may be modifying serologic food allergy severity assessments. Given these limitations, allergy test selection requires a shared decision-making approach so that a patient's values and preferences regarding financial impact, inconvenience, and psychological effects are considered in the context of clinician expertise on the timing and use of optimized testing., Competing Interests: Disclosures Dr Golden is a consultant for Novartis, Aquestive, and Kokua and has received clinical trials support from Genentech, Novartis, Pfizer, GlaxoSmithKline, Merck, Regeneron, and AstraZeneca. Dr Brough reports receiving research grants from the NIH (NIAAD) and speaker fees from DBV Technologies. Dr Santos reports receiving grants from Medical Research Council (MR/M008517/1; MC/PC/18052; and MR/T032081/1), Food Allergy Research and Education, the Immune Tolerance Network/National Institute of Allergy and Infectious Diseases (NIAID and NIH), Asthma UK (AUK-BC-2015-01), BBSRC, Rosetrees Trust, and the NIHR through the Biomedical Research Centre award to Guy's and St Thomas' NHS Foundation Trust, during the conduct of the study; receiving personal fees from Thermo Scientific, Nutricia, Infomed, Novartis, Allergy Therapeutics, and Buhlmann; and receiving research support from Buhlmann and Thermo Fisher Scientific through a collaboration agreement with King's College London. Dr Shaker is a member and co-chair of the Joint Task Force on Practice Parameters; serves on the editorial board of The Journal of Allergy and Clinical Immunology In Practice; is an associate editor of Annals of Allergy, Asthma & Immunology; serves on the board of directors of the American Academy of Allergy, Asthma, and Immunology (views expressed are his own); and has participated in research that has received funding from DBV. Dr Conway has no conflicts of interest to report., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Basophil activation test (BAT) or the mast cell activation test (MAT) are two in vitro tests that are currently being studied in food allergy as diagnostic tools as an alternative to oral food challenges (OFCs). We conducted a meta-analysis on BAT and MAT, assessing their specificity and sensitivity in diagnosing peanut allergy. Six databases were searched for studies on patients suspected of having peanut allergy. Studies using BAT or MAT to peanut extract and/or component as diagnostic tools with results given in percentage of CD63 activation were included in this meta-analysis. Study quality was evaluated with the QUADAS-2 tool. On the 11 studies identified, eight focused exclusively on children, while three included a mixed population of adults and children. Only one study provided data on MAT, precluding us from conducting a statistical analysis. The diagnostic accuracy of BAT was higher when stimulated with peanut extract rather than Ara h 2 with a pooled specificity of 96% (95% CI: 0.89-0.98) and sensitivity of 0.86 (95% CI: 0.74-0.93). The sensitivity and specificity of BATs in discriminating between allergic and sensitized patients were studied as well, with pooled analysis revealing a sensitivity of 0.86 (95% CI: 0.74; 0.93) and a specificity of 0.97 (95% CI: 0.94, 0.98). BATs, when stimulated with peanut extracts, exhibit a satisfactory sensitivity and specificity for the diagnosis of peanut allergy and can help to discriminate between allergic individuals and those only sensitized to peanuts. More investigations on the potential for MATs diagnostic methods are warranted., (© 2024 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

The cystine/glutamate antiporter xCT is an important source of cysteine for cancer cells. Once taken up, cystine is reduced to cysteine and serves as a building block for the synthesis of glutathione, which efficiently protects cells from oxidative damage and prevents ferroptosis. As melanomas are particularly exposed to several sources of oxidative stress, we investigated the biological role of cysteine and glutathione supply by xCT in melanoma. xCT activity was abolished by genetic depletion in the Tyr::CreER; Braf CA ; Pten lox/+ melanoma model and by acute cystine withdrawal in melanoma cell lines. Both interventions profoundly impacted melanoma glutathione levels, but they were surprisingly well tolerated by murine melanomas in vivo and by most human melanoma cell lines in vitro. RNA sequencing of human melanoma cells revealed a strong adaptive upregulation of NRF2 and ATF4 pathways, which orchestrated the compensatory upregulation of genes involved in antioxidant defence and de novo cysteine biosynthesis. In addition, the joint activation of ATF4 and NRF2 triggered a phenotypic switch characterized by a reduction of differentiation genes and induction of pro-invasive features, which was also observed after erastin treatment or the inhibition of glutathione synthesis. NRF2 alone was capable of inducing the phenotypic switch in a transient manner. Together, our data show that cystine or glutathione levels regulate the phenotypic plasticity of melanoma cells by elevating ATF4 and NRF2., Competing Interests: Declaration of competing interest The authors report no declarations of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Sporotrichosis is a mycotic infection of the cutaneous and subcutaneous tissues caused by Sporothrix spp. that can also cause extracutaneous manifestations. This study aimed to characterize cutaneous and extracutaneous sporotrichosis lesions in cats. Over 1 year, 102 cats rescued by the Zoonoses Control Center of Belo Horizonte, Brazil, euthanized with clinical suspicion of feline sporotrichosis were evaluated. After euthanasia, the animals were evaluated by macroscopic, cytological, histopathological, and immunohistochemistry (IHC) examinations; fungal culture; and polymerase chain reaction (PCR). Sporothrix infection was identified by at least one diagnostic technique in all cats (n = 102) evaluated by postmortem examination, including 26/28 cases (93%) evaluated by IHC, 66/90 cases (73%) evaluated by cytology, 70/102 cases (68.6%) evaluated by histopathology, and 62/74 cases (84%) evaluated by fungal culture. Two cats had positive results only by fungal culture. Cytology and histopathology examinations were effective in diagnosing sporotrichosis, although IHC was needed to confirm the diagnosis in cats with low fungal loads. Sporothrix brasiliensis was confirmed by the sequencing of 3 samples. Skin lesions were characterized mainly by pyogranulomatous to granulomatous dermatitis (frequently with subcutaneous inflammation) with different intensities of Sporothrix spp. yeast. Extracutaneous findings associated with sporotrichosis included rhinitis or rhinosinusitis, lymphadenitis, pneumonia, meningitis, periorchitis, conjunctivitis, and glossitis. Extracutaneous infections were observed in 74/102 cases, and a possible association between the chronicity of the disease and the higher pathogenicity of this fungal species in cats requires further investigation., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Many children are consuming some egg when they are diagnosed with egg allergy. We hypothesized that egg consumption could modify the diagnostic performance of allergy tests., Objective: To stratify diagnostic performance of tests according to egg consumption status., Methods: The BAT2 study (NCT03309488) participants underwent oral food challenge (OFC), food-frequency questionnaires, skin prick test (SPT), specific immunoglobulin E (sIgE) and specific immunoglobulin G4 (sIgG4) and basophil activation test (BAT)., Results: At study entry, 45% of participants reported partial egg consumption ("consumers") and 55% were avoiding egg strictly ("avoiders"). Avoiders had larger SPT (P < .001), higher BAT to egg (P < .001), sIgE to egg white (EW; P = .001) and to ovalbumin (OVA; P = .001), but not to ovomucoid (P = .231). Consumers had higher levels of sIgG4 to all egg allergens (P < .001) than avoiders. In consumers, the test with the best diagnostic performance was BAT (area under the curve [AUC] = .912) followed by SPT to raw egg (AUC = 0.805), EW-sIgE (AUC = 0.738), and OVA-sIgE (AUC = 0.732). In avoiders, the best tests were BAT (AUC = 0.834) and EW-sIgE (AUC = 0.833) followed by OVA-sIgE (AUC = 0.793) and SPT to EW (AUC=0.789). Using 100% sensitivity and 100% specificity cut-offs, the proportion of patients requiring OFC were 33% for BAT, 53% for SPT to raw egg, 61% for OVA-sIgE, and 73% for EW-sIgE for consumers; and 73% for BAT, 79% for EW-sIgE, and 93% for SPT to EW for avoiders., Conclusions: The diagnostic performance of tests is influenced by the immunomodulatory effect of egg consumption. BAT is the most reliable test and reduced the need for OFC, particularly in partial egg consumers., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Brazilian citrus farming has been migrating to nontraditional citrus-growing regions, which can be considered a challenge for citrus growers, as not all these areas are suitable for tangerine cultivation. Thus, the mapping of regions exhibiting favorable climatic conditions for Alternaria brown spot has become crucial in the selection of appropriate locations for the establishment of new orchards. This mapping enables the implementation of an avoidance strategy, which entails steering clear of areas where the disease is prevalent, aligning with fundamental principles of disease control., Results: Thus, this study seeks to zone areas with high and low climatic favorability for the occurrence of Alternaria brown spot in tangerine trees in Brazil. Historical climate data series from the NASA-POWER database were used for all municipalities in Brazil. Agrometeorological variables used to determine the development of Alternaria brown spot were average monthly air temperature (Tmean) and duration of leaf wetness period (LWD). Areas were considered unsuitable climatically when Tmean was <17 °C or >33 °C, relatively suitable when Tmean was between 13 °C and 33 °C and LWD <10%, and climatically suitable when Tmean was between 13 °C and 33 °C and LWD >10%. The states of Paraná, Santa Catarina and Rio Grande do Sul showed greater thermal amplitude within months and throughout the year. The southern region of the country has harsher winters, with minimum temperatures below 15 °C, which is unfavorable for the disease incidence., Conclusion: The states with the greatest favorability for Alternaria brown spot were Paraná, Santa Catarina, and Rio Grande do Sul, mainly from May to September. Rio Grande do Sul was the state in this region that showed the greatest favorability, as a consequence of leaf wetness exceeding 10 h. The main tangerine-producing regions in Brazil, including the southern part of Minas Gerais, the state of São Paulo and the metropolitan region of Porto Alegre, were mostly classified as relatively favorable areas for the occurrence of Alternaria brown spot. It is recommended that when establishing new tangerine orchards, regions with lower favorability for the occurrence of Alternaria brown spot, such as the North and Central-West regions of Brazil, particularly the states of Amazonas, Pará and Mato Grosso, should be selected. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

A review of the latest publications in food allergy over the past couple of years confirmed that food allergy is a major public health concern, affecting about 8% of children and 10% of adults in developed countries. The prevalence of food allergy varies around the world, with the increase being driven mainly by environmental factors, possibly together with genetic susceptibility to environmental changes. A precise diagnosis of food allergy is extremely important. Both new tests (eg, the basophil activation test) and improved optimization of information provided by existing tests (eg, the skin prick test and measurement of specific IgE level) can contribute to improving the accuracy and patients' comfort of food allergy diagnosis. Understanding the underlying immune mechanisms is fundamental to designing allergen-specific treatments that can be safe and effective in the long term. New discoveries of the immune response to food allergens, including T-cell and B-cell responses, have emerged. Novel therapeutic approaches are being trialed at various stages of development as attempts to allow for more active intervention to treat food allergy. Prevention is key to reducing the increase in prevalence. Early introduction of allergenic foods seems to be the most effective intervention, but others are being studied, and will, it is hoped, lead to modification of the epidemiologic trajectory of food allergy over time., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Phosphorus (P) removal from urban wastewater is increasingly relevant in the wastewater treatment sector. The present work aims to contribute to the study of the adsorption process as a P removal technology. Biogenic calcium carbonate from industrial eggshell waste prepared by milling and calcination was used as an adsorbent. Batch adsorption experiments were conducted using real wastewater with 40 mg P/L (orthophosphate), original pH 7.33, under stirring conditions (100 rpm). The adsorbent was characterized using SEM-EDS, XRD, and FTIR-ATR before and after adsorption. From an initial screening of calcination times (15, 30, 60, and 120 min) and considering a balance between P removal and energy saving, the adsorbent selected was eggshell calcined at 700 °C for 60 min. The Langmuir isotherms describe the experimental data with a maximum adsorption capacity of 4.57 mg P/g at 25 °C. The adsorption process reached equilibrium within 120 min for different dosages (5, 10, and 20 g/L at 25 °C). Batch experiments showed that SO 4 2- , at a concentration of 2689 mg/L reduced the P adsorption selectivity for dosages ≤10 g/L at 25 °C. Characterization of the loaded adsorbent shows that P adsorption from real wastewater is mostly electrostatic attraction, with the contribution of ligand exchange and microprecipitation. The adsorption capacity and behavior of the selected adsorbent seem promising for P removal from urban wastewater compared with other low-cost adsorbents., 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 © 2023 Elsevier Ltd. All rights reserved.)

The European Academy of Allergy and Clinical Immunology (EAACI) is updating the Guidelines on Food Allergy Diagnosis. We aimed to undertake a systematic review of the literature with meta-analyses to assess the accuracy of diagnostic tests for IgE-mediated food allergy. We searched three databases (Cochrane CENTRAL (Trials), MEDLINE (OVID) and Embase (OVID)) for diagnostic test accuracy studies published between 1 October 2012 and 30 June 2021 according to a previously published protocol (CRD42021259186). We independently screened abstracts, extracted data from full texts and assessed risk of bias with QUADRAS 2 tool in duplicate. Meta-analyses were undertaken for food-test combinations for which three or more studies were available. A total of 149 studies comprising 24,489 patients met the inclusion criteria and they were generally heterogeneous. 60.4% of studies were in children ≤12 years of age, 54.3% were undertaken in Europe, ≥95% were conducted in a specialized paediatric or allergy clinical setting and all included oral food challenge in at least a percentage of enrolled patients, in 21.5% double-blind placebo-controlled food challenges. Skin prick test (SPT) with fresh cow's milk and raw egg had high sensitivity (90% and 94%) for milk and cooked egg allergies. Specific IgE (sIgE) to individual components had high specificity: Ara h 2-sIgE had 92%, Cor a 14-sIgE 95%, Ana o 3-sIgE 94%, casein-sIgE 93%, ovomucoid-sIgE 92/91% for the diagnosis of peanut, hazelnut, cashew, cow's milk and raw/cooked egg allergies, respectively. The basophil activation test (BAT) was highly specific for the diagnosis of peanut (90%) and sesame (93%) allergies. In conclusion, SPT and specific IgE to extracts had high sensitivity whereas specific IgE to components and BAT had high specificity to support the diagnosis of individual food allergies., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Ferroptosis is a form of cell death that has received considerable attention not only as a means to eradicate defined tumour entities but also because it provides unforeseen insights into the metabolic adaptation that tumours exploit to counteract phospholipid oxidation 1,2 . Here, we identify proferroptotic activity of 7-dehydrocholesterol reductase (DHCR7) and an unexpected prosurvival function of its substrate, 7-dehydrocholesterol (7-DHC). Although previous studies suggested that high concentrations of 7-DHC are cytotoxic to developing neurons by favouring lipid peroxidation 3 , we now show that 7-DHC accumulation confers a robust prosurvival function in cancer cells. Because of its far superior reactivity towards peroxyl radicals, 7-DHC effectively shields (phospho)lipids from autoxidation and subsequent fragmentation. We provide validation in neuroblastoma and Burkitt's lymphoma xenografts where we demonstrate that the accumulation of 7-DHC is capable of inducing a shift towards a ferroptosis-resistant state in these tumours ultimately resulting in a more aggressive phenotype. Conclusively, our findings provide compelling evidence of a yet-unrecognized antiferroptotic activity of 7-DHC as a cell-intrinsic mechanism that could be exploited by cancer cells to escape ferroptosis., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Identifying patients at risk of severe allergic reactions and/or low threshold of reactivity is very important, particularly for staple foods like egg., Methods: One hundred and fifty children underwent double-blind placebo-controlled food challenge (DBPCFC) to baked egg (BE), skin prick testing and blood collection for serology and basophil activation test (BAT). Patients who passed BE DBPCFC underwent loosely cooked egg (LCE) DBPCFC. Severity of allergic reactions was classified following Practall guidelines and threshold dose was determined during DBPCFC., Results: Sixty out of 150 (40%) children reacted to BE and 16 out of 77 (21%) to LCE on DBPCFC. Considering DBPCFC to BE, 23 children (38%) had severe reactions and 33 (55%) reacted to 0.13 g or less of egg protein (low threshold group). Two children (2 out of 16 = 12%) had severe reactions to LCE. Demographic, clinical and most immunological features were not significantly different between severe/non-severe BE reactors or low/high threshold groups. Severe BE reactors had higher ovomucoid-sIgE (p = .009) and higher BAT to BE (p = .001). Patients with lower threshold to BE had higher IgE-specific activity (p = .027) and BAT to egg (p = .007) but lower severity score (p = .008). Optimal cut-offs for ovomucoid-sIgE had 100% sensitivity, 35% specificity and 60% accuracy and for BAT 76% sensitivity, 74% specificity and 75% accuracy to identify BE severe reactors. Optimal cut-offs for specific activity had 70% sensitivity, 68% specificity and 69% accuracy and for BAT 70% sensitivity, 72% specificity and 71% accuracy to identify low threshold patients., Conclusions: BAT was the best biomarker to predict severity and threshold of allergic reactions to BE and can be useful when making decisions about management of egg allergy., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

An operative olfactory bulb (OB) is critical to social recognition memory (SRM) in rodents, which involves identifying conspecifics. Furthermore, OB also allocates synaptic plasticity events related to olfactory memories in their intricate neural circuit. Here, we asked whether the OB is a target for brain-derived neurotrophic factor (BDNF), a well-known mediator of plasticity and memory. Adult ICR-CD1 male mice had their SRM evaluated under the inhibition of BDNF-dependent signaling directly in the OB. We also quantified the expression of BDNF in the OB, after SRM acquisition. Our results presented an amnesic effect of anti-BDNF administered 12 h post-training. Although the western blot showed no statistical difference in pro-BDNF and BDNF expression, the analysis of fluorescence intensity in slices suggests SRM acquisition decreases BDNF in the granular cell layer of the OB. Next, to test the ability of BDNF to rescue SRM deficit, we administered the human recombinant BDNF (rBDNF) directly in the OB of socially isolated (SI) mice. Unexpectedly, rBDNF did not rescue SRM in SI mice. Furthermore, BDNF and pro-BDNF expression in the OB was unchanged by SI. Our study reinforces the OB as a plasticity locus in memory-related events. It also adds SRM as another type of memory sensitive to BDNF-dependent signaling., 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 © 2024. Published by Elsevier Inc.)