Nutritional Considerations of Plant-Based Diets for People With Food Allergy.

Plant-based diets (PBD) have been reported throughout history, but are increasingly common in current times, likely in part due to considerable emphasis on climate change and human health and wellness. Many dietary organisations around the world endorse well-planned, nutritionally adequate PBD, which exclude some or all forms of animal-based foods. However, special attention must be given to patients who follow PBD and also have food allergy (FA), as avoidance may increase the risk of developing nutritional deficiencies, including poor growth in children, weight loss in adults and vitamin and mineral deficiencies. Given the increasing prevalence of both PBD and food allergen avoidance diets, healthcare providers are likely to counsel patients with FA who also follow a PBD. In this review, an overview of PBD in patients with FA is provided, including recent trends, macro- and micronutrient needs, and growth for children and weight gain considerations for adults. With regard to a PBD, special attention should be given to ensure adequate fat and protein intake and improving the bioavailability of several minerals such as iron, zinc, iodine, calcium and magnesium, and vitamins such as A, B2, B12 and D. Although the collective data on growth amongst children following a PBD are varied in outcome and may be influenced in part by the type of PBD, growth must be regularly monitored and in adults weight gain assessed as part of any clinical assessment in those people with FA.

Ultra-processed foods, allergy outcomes and underlying mechanisms in children: An EAACI task force report.

BACKGROUND: Consumption of ultra-processed foods [UPFs] may be associated with negative health outcomes. Limited data exist regarding the potential role of UPFs in the occurrence of allergic diseases. The underlying mechanisms underpinning any such associations are also poorly elucidated. METHODS: We performed a systematic review and narrative evidence synthesis of the available literature to assess associations between UPF consumption and pediatric allergy outcomes (n = 26 papers), including data on the association seen with the gut microbiome (n = 16 papers) or immune system (n = 3 papers) structure and function following PRISMA guidelines. RESULTS: Dietary exposure to fructose, carbonated soft drinks, and sugar intake was associated with an increased risk of asthma, allergic rhinitis, and food allergies in children. Commercial baby food intake was associated with childhood food allergy. Childhood intake of fructose, fruit juices, sugar-sweetened beverages, high carbohydrate UPFs, monosodium glutamate, UPFs, and advanced glycated end-products (AGEs) was associated with the occurrence of allergic diseases. Exposure to UPFs and common ingredients in UPFs seem to be associated with increased occurrence of allergic diseases such as asthma, wheezing, food allergies, atopic dermatitis, and allergic rhinitis, in many, but not all studies. CONCLUSION: More preclinical and clinical studies are required to better define the link between UPF consumption and the risk of allergies and asthma. These observational studies ideally require supporting data with clearly defined UPF consumption, validated dietary measures, and mechanistic assessments to definitively link UPFs with the risk of allergies and asthma.

Adjuvant (chemo)radiotherapy for patients with head and neck cancer: can comorbidity risk scores predict outcome?

PURPOSE: This study compares the objective American Society of Anesthesiologists (ASA) and Adult Comorbidity Evaluation-27 (ACE-27) scores with the subjective Eastern Cooperative Oncology Group performance status (ECOG PS) for patient outcome prediction. METHODS: We retrospectively analyzed head and neck squamous cell carcinoma patients treated with adjuvant (chemo)radiotherapy at the LMU Munich from June 2008 to June 2015. The study focused on associations between patient outcomes; treatment failures; known risk factors (including human papillomavirus [HPV] status and tumor stage); and the comorbidity indices ECOG-PS, ASA score, and ACE-27. The Kaplan-Meier method and Cox proportional hazards model were used for survival analysis and identifying independent risk factors. RESULTS: A total of 302 patients were analyzed, 175 received concurrent chemotherapy. Median follow-up was 61.8 months, and median age at diagnosis was 61 years. The 3­ and 5­year overall survival (OS) and disease-free survival (DFS) rates were 70.5%/60.2% and 64.7%/57.6%, respectively. Both ACE-27 and ASA showed significant correlations with OS in univariate and multivariate analyses, while ECOG-PS was significant only in univariate analysis. ASA and ACE-27 scores were also significantly correlated with local and locoregional recurrence, but only HPV status and tumor stage were significant in multivariate models. CONCLUSION: ACE-27 and ASA score effectively categorize patients' risks in adjuvant radiotherapy for head and neck cancer, proving more predictive of overall survival than ECOG-PS. These results underscore the importance of objective comorbidity assessment and suggest further prospective studies.

Malnutrition and Allergies: Tipping the Immune Balance towards Health.

Malnutrition, which includes macro- and micronutrient deficiencies, is common in individuals with allergic dermatitis, food allergies, rhinitis, and asthma. Prolonged deficiencies of proteins, minerals, and vitamins promote Th2 inflammation, setting the stage for allergic sensitization. Consequently, malnutrition, which includes micronutrient deficiencies, fosters the development of allergies, while an adequate supply of micronutrients promotes immune cells with regulatory and tolerogenic phenotypes. As protein and micronutrient deficiencies mimic an infection, the body's innate response limits access to these nutrients by reducing their dietary absorption. This review highlights our current understanding of the physiological functions of allergenic proteins, iron, and vitamin A, particularly regarding their reduced bioavailability under inflamed conditions, necessitating different dietary approaches to improve their absorption. Additionally, the role of most allergens as nutrient binders and their involvement in nutritional immunity will be briefly summarized. Their ability to bind nutrients and their close association with immune cells can trigger exaggerated immune responses and allergies in individuals with deficiencies. However, in nutrient-rich conditions, these allergens can also provide nutrients to immune cells and promote health.

Tumor board simulation improves interdisciplinary decision-making in medical students.

INTRODUCTION: Training of interdisciplinary clinical reasoning and decision-making skills, essential in daily clinical practice in oncological specialties, are still underrepresented in medical education. Therefore, at LMU University Hospital Munich, we implemented a didactically modified tumor board simulation with experts from five different disciplines (medical oncology, pathology, radiation oncology, radiology, and surgery) presenting patient cases into a one-week course on the basic principles of oncology. In this survey, we examined the self-assessed impact of our course on the interdisciplinary decision-making skills of medical students. METHODS: Between November-December 2023 and January-February 2024, we surveyed two cohorts of medical students in the third year of medical school in our one-week course before and after participating in the tumor board simulation. The objective was to evaluate the self-assessed knowledge in interdisciplinary clinical decision-making, in integrating ethical considerations into clinical reasoning, and in comprehension of various professional viewpoints in interdisciplinary decision-making. Knowledge was assessed using a five-step Likert scale from 1 (no knowledge) to 5 (complete knowledge). RESULTS: The survey was answered by 76 students before and 55 after the simulation, equaling 60-70% of all 100 course participants. Mean knowledge level regarding principles of interdisciplinary clinical decision-making improved significantly in all of the following exemplary aspects: purpose and procedure of tumor boards in clinical practice (from 2.4 ± 1.1 to 4.0 ± 1.0, Spearman's ρ = 0.6, p < 0.001), principles of dealing with ethical challenges in oncology (from 2.4 ± 1.1 to 3.4 ± 1.0, ρ = 0.4, p < 0.001), and principles of shared decision-making in oncology (2.7 ± 1.1 to 3.7 ± 1.0, ρ = 0.4, p < 0.001). Students reported that their skills in clinical decision-making and ability to discuss oncological patient cases from different professional viewpoints improved due to the teaching course. CONCLUSION: By employing our interdisciplinary one-week course and a didactically modified tumor board simulation featuring experts from various oncological disciplines, medical students' comprehension of interdisciplinary clinical decision-making in oncology improved significantly.

The Effects of Language Background and Parental Education on Measures of Cognitive Ability: An Analysis of the WPPSI-IV Cognitive Profiles of Monolingual, Simultaneous Bilingual, and Sequential Bilingual German Children Aged 4 to 7 Years.

BACKGROUND: The present study investigated the possible effects of language background (monolinguals, simultaneous bilinguals, and sequential bilinguals) and parental education (no/low, medium, high, and highest parental education) on measures of cognitive ability provided by the Wechsler Primary and Preschool Scale-Fourth Edition (WPPSI-IV). METHODS: Statistical analyses were based on a sample of 290 children (130 females, 160 males). Three multivariate variance analyses were conducted to identify possible effects. In cases of statistically significant main effects, post hoc analyses were additionally performed to identify group differences. RESULTS: The results indicated that simultaneous bilinguals performed more similarly to monolinguals than sequential bilinguals. On average, sequential bilinguals achieved significantly lower scores on the Verbal Comprehension Index (VCI), the Vocabulary Acquisition Index (VAI), and the associated subtests than monolinguals and simultaneous bilinguals. Significantly lower average scores on VAI and the associated subtests were found for simultaneous bilinguals compared to monolinguals. Children with parents having no, a lower, or a medium educational level achieved significantly lower scores on VCI, VAI, and the FSIQ than children with parents having a high or highest educational level on average. CONCLUSIONS: The present findings suggest that the WPPSI-IV represents a suitable and reliable test battery for the assessment of cognitive skills in children with different language backgrounds and parental educational levels.

A systematic review and meta-analysis of nutritional and dietary interventions in randomized controlled trials for skin symptoms in children with atopic dermatitis and without food allergy: An EAACI task force report.

This systematic review and meta-analysis aimed to consolidate evidence on dietary interventions for atopic eczema/dermatitis (AD) skin symptoms in children without food allergies, following PRISMA 2020 guidelines. Systematic review updates were conducted in May 2022 and June 2023, focusing on randomized placebo-controlled trials (RCTs) involving children with AD but without food allergies. Specific diets or supplements, such as vitamins, minerals, probiotics, prebiotics, symbiotics, or postbiotics, were explored in these trials. Exclusions comprised descriptive studies, systematic reviews, meta-analyses, letters, case reports, studies involving elimination diets, and those reporting on food allergens in children and adolescents. Additionally, studies assessing exacerbation of AD due to food allergy/sensitization and those evaluating elimination diets' effects on AD were excluded. Nutritional supplementation studies were eligible regardless of sensitization profile. Evaluation of their impact on AD clinical expression was performed using SCORAD scores, and a meta-analysis of SCORAD outcomes was conducted using random-effect models (CRD42022328702). The review encompassed 27 RCTs examining prebiotics, Vitamin D, evening primrose oil, and substituting cow's milk formula with partially hydrolyzed whey milk formula. A meta-analysis of 20 RCTs assessing probiotics, alone or combined with prebiotics, revealed a significant reduction in SCORAD scores, suggesting a consistent trend in alleviating AD symptoms in children without food allergies. Nonetheless, evidence for other dietary interventions remains limited, underscoring the necessity for well-designed intervention studies targeting multiple factors to understand etiological interactions and propose reliable manipulation strategies.

Mould allergen Alt a 1 spiked with the micronutrient retinoic acid reduces Th2 response and ameliorates Alternaria allergy in BALB/c mice.

BACKGROUND: We investigated the biological function of the mould allergen Alt a 1 as a carrier of micronutrients, such as the vitamin A metabolite retinoic acid (RA) and the influence of RA binding on its allergenicity in vitro and in vivo. METHODS: Alt a 1-RA complex formation was analyzed in silico and in vitro. PBMCs from Alternaria-allergic donors were stimulated with Alt a 1 complexed with RA (holo-Alt a 1) or empty apo-Alt a 1 and analyzed for cytokine production and CD marker expression. Serum IgE-binding and crosslinking assays to apo- and holo-protein were correlated to B-cell epitope analysis. Female BALB/c mice already sensitized to Alt a 1 were intranasally treated with apo-Alt a 1, holo-Alt a 1 or RA alone before measuring anaphylactic response, serum antibody levels, splenic cytokines and CD marker expression. RESULTS: In silico docking calculations and in vitro assays showed that the extent of RA binding depended on the higher quaternary state of Alt a 1. Holo-Alt a 1 loaded with RA reduced IL-13 released from PBMCs and CD3+CD4+CRTh2 cells. Complexing Alt a 1 to RA masked its IgE B-cell epitopes and reduced its IgE-binding capacity. In a therapeutic mouse model of Alternaria allergy nasal application of holo-Alt a 1, but not of apo-Alt a 1, significantly impeded the anaphylactic response, impaired splenic antigen-presenting cells and induced IL-10 production. CONCLUSION: Holo-Alt a 1 binding to RA was able to alleviate Th2 immunity in vitro, modulate an ongoing Th2 response and prevent anaphylactic symptoms in vivo, presenting a novel option for improving allergen-specific immunotherapy in Alternaria allergy.

Hematologic Toxicity and Bone Marrow-Sparing Strategies in Chemoradiation for Locally Advanced Cervical Cancer: A Systematic Review.

The standard treatment for locally advanced cervical cancer typically includes concomitant chemoradiation, a regimen known to induce severe hematologic toxicity (HT). Particularly, pelvic bone marrow dose exposure has been identified as a contributing factor to this hematologic toxicity. Chemotherapy further increases bone marrow suppression, often necessitating treatment interruptions or dose reductions. A systematic search for original articles published between 1 January 2006 and 7 January 2024 that reported on chemoradiotherapy for locally advanced cervical cancer and hematologic toxicities was conducted. Twenty-four articles comprising 1539 patients were included in the final analysis. HT of grade 2 and higher was observed across all studies and frequently exceeded 50%. When correlating active pelvic bone marrow and HT, significant correlations were found for volumes between 10 and 45 Gy and HT of grade 3 and higher. Several dose recommendations for pelvic bone and pelvic bone marrow sparing to reduce HT were established, including V10 < 90-95%, V20 < 65-86.6% and V40 < 22.8-40%. Applying dose constraints to the pelvic bone/bone marrow is a promising approach for reducing HT, and thus reliable implementation of therapy. However, prospective randomized controlled trials are needed to define precise dose constraints and optimize clinical strategies.

Metabolic pathway-based subtypes associate glycan biosynthesis and treatment response in head and neck cancer.

Head and Neck Squamous Cell Carcinoma (HNSCC) is a heterogeneous malignancy that remains a significant challenge in clinical management due to frequent treatment failures and pronounced therapy resistance. While metabolic dysregulation appears to be a critical factor in this scenario, comprehensive analyses of the metabolic HNSCC landscape and its impact on clinical outcomes are lacking. This study utilized transcriptomic data from four independent clinical cohorts to investigate metabolic heterogeneity in HNSCC and define metabolic pathway-based subtypes (MPS). In HPV-negative HNSCCs, MPS1 and MPS2 were identified, while MPS3 was enriched in HPV-positive cases. MPS classification was associated with clinical outcome post adjuvant radio(chemo)therapy, with MPS1 consistently exhibiting the highest risk of therapeutic failure. MPS1 was uniquely characterized by upregulation of glycan (particularly chondroitin/dermatan sulfate) metabolism genes. Immunohistochemistry and pilot mass spectrometry imaging analyses confirmed this at metabolite level. The histological context and single-cell RNA sequencing data identified the malignant cells as key contributors. Globally, MPS1 was distinguished by a unique transcriptomic landscape associated with increased disease aggressiveness, featuring motifs related to epithelial-mesenchymal transition, immune signaling, cancer stemness, tumor microenvironment assembly, and oncogenic signaling. This translated into a distinct histological appearance marked by extensive extracellular matrix remodeling, abundant spindle-shaped cancer-associated fibroblasts, and intimately intertwined populations of malignant and stromal cells. Proof-of-concept data from orthotopic xenotransplants replicated the MPS phenotypes on the histological and transcriptome levels. In summary, this study introduces a metabolic pathway-based classification of HNSCC, pinpointing glycan metabolism-enriched MPS1 as the most challenging subgroup that necessitates alternative therapeutic strategies.

Efficacy and Safety of Local Liver Radioablation in Hepatocellular Carcinoma Lesions within and beyond Limits of Thermal Ablation.

INTRODUCTION: CT-guided interstitial brachytherapy (iBT) radiotherapy has been established in the treatment of liver tumors. With iBT, hepatocellular carcinoma (HCC) lesions can be treated beyond the limits of thermal ablation (i.e., size and location). However, a comprehensive analysis of the efficacy of iBT in patients within and beyond thermal ablation limits is lacking. MATERIALS AND METHODS: A total of 146 patients with 216 HCC lesions have been analyzed retrospectively. Clinical and imaging follow-up data has been collected. Lesions were evaluated in terms of suitability for thermal ablation or not. The correlation between local tumor control (LTC), time to progression (TTP), overall survival (OS), and clinical and imaging parameters have been evaluated using univariable and multivariable Cox regression analyses. RESULTS: LTC rates at 12 months, 24 months, and 36 months were 87%, 75%, and 73%, respectively. 65% of lesions (n = 141) were not suitable for radiofrequency ablation (RFA). The median TTP was 13 months, and the median OS was not reached (3-year OS rate: 70%). No significant difference in LTC, TTP, or OS regarding RFA suitability existed. However, in the overall multivariable analysis, lesion diameter >5 cm was significantly associated with lower LTC (HR: 3.65, CI [1.60-8.31], p = 0.002) and shorter TTP (HR: 2.08, CI [1.17-3.70], p = 0.013). Advanced BCLC stage, Child-Pugh Stage, and Hepatitis B were associated with shorter OS. CONCLUSION: iBT offers excellent LTC rates and OS in local HCC treatment regardless of the limits of thermal ablation, suggesting further evidence of its alternative role to thermal ablation in patients with early-stage HCC.

Dietary management of IgE and non-IgE-mediated food allergies in pediatric patients.

Food allergies (FA) consist of both IgE and non-IgE-mediated entities, with varying phenotypes and overlapping and different considerations for each specific disease presentation. In general, all FAs place children at increased risk for inadequate nutritional intake and negative impacts on their nutritional status, as well as negative impacts on the quality of life for the entire family. To minimize these untoward effects, a multidisciplinary approach should be taken, including consultation and management with a dietitian trained in the varying presentations of FA. Families should be instructed on label reading as a first line of nutritional management. During a nutrition consultation, the age of the child, growth, and nutritional status should be considered. Food refusal should be assessed and addressed. Families should be educated on avoidance and appropriate substitutions. In the case of cow's milk allergy, a suitable specialized formula should be suggested if the infant is not breastfed or if breast milk supply is not sufficient. Other mammalian milk should be avoided and careful consideration should be given before plant-based milk is used in young children. Specific food allergies may differ in terms of advice provided on the level of avoidance required, whether precautionary advisory labels should be avoided, and if a maternal avoidance of the allergen during breastfeeding should be advised. The role of immunonutrition on overall health should be discussed.

Stereotactic body radiotherapy for pancreatic cancer - A systematic review of prospective data.

Purpose: This systematic review aims to comprehensively summarize the current prospective evidence regarding Stereotactic Body Radiotherapy (SBRT) in various clinical contexts for pancreatic cancer including its use as neoadjuvant therapy for borderline resectable pancreatic cancer (BRPC), induction therapy for locally advanced pancreatic cancer (LAPC), salvage therapy for isolated local recurrence (ILR), adjuvant therapy after radical resection, and as a palliative treatment. Special attention is given to the application of magnetic resonance-guided radiotherapy (MRgRT). Methods: Following PRISMA guidelines, a systematic review of the Medline database via PubMed was conducted focusing on prospective studies published within the past decade. Data were extracted concerning study characteristics, outcome measures, toxicity profiles, SBRT dosage and fractionation regimens, as well as additional systemic therapies. Results and conclusion: 31 studies with in total 1,571 patients were included in this review encompassing 14 studies for LAPC, 9 for neoadjuvant treatment, 2 for adjuvant treatment, 2 for ILR, with an additional 4 studies evaluating MRgRT. In LAPC, SBRT demonstrates encouraging results, characterized by favorable local control rates. Several studies even report conversion to resectable disease with substantial resection rates reaching 39%. The adoption of MRgRT may provide a solution to the challenge to deliver ablative doses while minimizing severe toxicities. In BRPC, select prospective studies combining preoperative ablative-dose SBRT with modern induction systemic therapies have achieved remarkable resection rates of up to 80%. MRgRT also holds potential in this context. Adjuvant SBRT does not appear to confer relevant advantages over chemotherapy. While prospective data for SBRT in ILR and for palliative pain relief are limited, they corroborate positive findings from retrospective studies.

Nutrition in chronic inflammatory conditions: Bypassing the mucosal block for micronutrients.

Nutritional Immunity is one of the most ancient innate immune responses, during which the body can restrict nutrients availability to pathogens and restricts their uptake by the gut mucosa (mucosal block). Though this can be a beneficial strategy during infection, it also is associated with non-communicable diseases-where the pathogen is missing; leading to increased morbidity and mortality as micronutritional uptake and distribution in the body is hindered. Here, we discuss the acute immune response in respect to nutrients, the opposing nutritional demands of regulatory and inflammatory cells and particularly focus on some nutrients linked with inflammation such as iron, vitamins A, Bs, C, and other antioxidants. We propose that while the absorption of certain micronutrients is hindered during inflammation, the dietary lymph path remains available. As such, several clinical trials investigated the role of the lymphatic system during protein absorption, following a ketogenic diet and an increased intake of antioxidants, vitamins, and minerals, in reducing inflammation and ameliorating disease.

Deep Learning and Registration-Based Mapping for Analyzing the Distribution of Nodal Metastases in Head and Neck Cancer Cohorts: Informing Optimal Radiotherapy Target Volume Design.

We introduce a deep-learning- and a registration-based method for automatically analyzing the spatial distribution of nodal metastases (LNs) in head and neck (H/N) cancer cohorts to inform radiotherapy (RT) target volume design. The two methods are evaluated in a cohort of 193 H/N patients/planning CTs with a total of 449 LNs. In the deep learning method, a previously developed nnU-Net 3D/2D ensemble model is used to autosegment 20 H/N levels, with each LN subsequently being algorithmically assigned to the closest-level autosegmentation. In the nonrigid-registration-based mapping method, LNs are mapped into a calculated template CT representing the cohort-average patient anatomy, and kernel density estimation is employed to estimate the underlying average 3D-LN probability distribution allowing for analysis and visualization without prespecified level definitions. Multireader assessment by three radio-oncologists with majority voting was used to evaluate the deep learning method and obtain the ground-truth distribution. For the mapping technique, the proportion of LNs predicted by the 3D probability distribution for each level was calculated and compared to the deep learning and ground-truth distributions. As determined by a multireader review with majority voting, the deep learning method correctly categorized all 449 LNs to their respective levels. Level 2 showed the highest LN involvement (59.0%). The level involvement predicted by the mapping technique was consistent with the ground-truth distribution (p for difference 0.915). Application of the proposed methods to multicenter cohorts with selected H/N tumor subtypes for informing optimal RT target volume design is promising.

Principles of oncology taught in a one-week course.

BACKGROUND: Growing challenges in oncology require evolving educational methods and content. International efforts to reform oncology education are underway. Hands-on, interdisciplinary, and compact course formats have shown great effectiveness in the education of medical students. Our aim was to establish a new interdisciplinary one-week course on the principles of oncology using state-of-the-art teaching methods. METHODS: In an initial survey, medical students of LMU Munich were questioned about their current level of knowledge on the principles of oncology. In a second two-stage survey, the increase in knowledge resulting from our recently established interdisciplinary one-week course was determined. RESULTS: The medical students' knowledge of clinically important oncological topics, such as the diagnostic workup and interdisciplinary treatment options, showed a need for improvement. Knowledge of the major oncological entities was also in an expandable state. By attending the one-week course on the principles of oncology, students improved their expertise in all areas of the clinical workup in oncology and had the opportunity to close previous knowledge gaps. In addition, students were able to gain more in-depth clinical knowledge on the most common oncological entities. CONCLUSION: The interdisciplinary one-week course on the principles of oncology proved to be an effective teaching method to expand the knowledge of the future physicians to an appropriate level. With its innovative and interdisciplinary approach, the one-week course could be used as a showcase project for the ongoing development of medical education in Germany.

Nutritional Provision of Iron Complexes by the Major Allergen Alt a 1 to Human Immune Cells Decreases Its Presentation.

Alternaria alternata is a common fungus strongly related with severe allergic asthma, with 80% of affected individuals being sensitized solely to its major allergen Alt a 1. Here, we assessed the function of Alt a 1 as an innate defense protein binding to micronutrients, such as iron-quercetin complexes (FeQ2), and its impact on antigen presentation in vitro. Binding of Alt a 1 to FeQ2 was determined in docking calculations. Recombinant Alt a 1 was generated, and binding ability, as well as secondary and quaternary structure, assessed by UV-VIS, CD, and DLS spectroscopy. Proteolytic functions were determined by casein and gelatine zymography. Uptake of empty apo- or ligand-filled holoAlt a 1 were assessed in human monocytic THP1 cells under the presence of dynamin and clathrin-inhibitors, activation of the Arylhydrocarbon receptor (AhR) using the human reporter cellline AZ-AHR. Human PBMCs were stimulated and assessed for phenotypic changes in monocytes by flow cytometry. Alt a 1 bound strongly to FeQ2 as a tetramer with calculated Kd values reaching pico-molar levels and surpassing affinities to quercetin alone by a factor of 5000 for the tetramer. apoAlt a 1 but not holoAlta 1 showed low enzymatic activity against casein as a hexamer and gelatin as a trimer. Uptake of apo- and holo-Alt a 1 occurred partly clathrin-dependent, with apoAlt a 1 decreasing labile iron in THP1 cells and holoAlt a 1 facilitating quercetin-dependent AhR activation. In human PBMCs uptake of holoAlt a 1 but not apoAlt a 1 significantly decreased the surface expression of the costimulatory CD86, but also of HLADR, thereby reducing effective antigen presentation. We show here for the first time that the presence of nutritional iron complexes, such as FeQ2, significantly alters the function of Alt a 1 and dampens the human immune response, thereby supporting the notion that Alt a 1 only becomes immunogenic under nutritional deprivation.

The holo beta-lactoglobulin lozenge reduces symptoms in cat allergy-Evaluation in an allergen exposure chamber and by titrated nasal allergen challenge.

BACKGROUND: The allergists´ tool box in cat allergy management is limited. Clinical studies have shown that holo beta-lactoglobulin (holoBLG) can restore micronutritional deficits in atopic immune cells and alleviate allergic symptoms in a completely allergen-nonspecific manner. With this study, we aimed to provide proof of principle in cat allergy. METHODS: A novel challenge protocol for cat allergy in a standardized ECARF allergen exposure chamber (AEC) was developed. In an open pilot study (NCT05455749), patients with clinically relevant cat allergy were provoked with cat allergen for 120 min in the AEC before and after a 3-month intervention phase (holoBLG lozenge 2x daily). Nasal, conjunctival, bronchial, and pruritus symptoms were scored every 10 min- constituting the total symptom score (TSS). Peak nasal inspiratory flow (PNIF) was measured every 30 min. In addition, a titrated nasal provocation test (NPT) was performed before and after the intervention. Primary endpoint was change in TSS at the end of final exposure compared to baseline. Secondary endpoints included changes in PNIF, NPT, and occurrence of late reactions up to 24 h after exposure. RESULTS: 35 patients (mean age: 40 years) completed the study. Compared to baseline, holoBLG supplementation resulted in significant improvement in median TSS of 50% (p < 0.001), as well as in median nasal flow by 20 L/min (p = 0.0035). 20% of patients reported late reactions after baseline exposure, but 0% after the final exposure. CONCLUSIONS: Cat allergic patients profited from targeted micronutrition with the holoBLG lozenge. As previously seen in other allergies, holoBLG supplementation also induced immune resilience in cat allergies, resulting in significant symptom amelioration.

Identifying the duration of emotional stimulus presentation for conscious versus subconscious perception via hierarchical drift diffusion models.

To investigate subliminal priming effects, different durations for stimulus presentation are applied ranging from 8 to 30 ms. This study aims to select an optimal presentation span whichleads to a subconscious processing. 40 healthy participants rated emotional faces (sad, neutral or happy expression) presented for 8.3 ms, 16.7 ms and 25 ms. Alongside subjective and objectivestimulus awareness, task performance was estimated via hierarchical drift diffusion models. Participants reported stimulus awareness in 65 % of the 25 ms trials,in 36 % of 16.7 ms trials, and in 2.5 % of 8.3 ms trials.Emotion-dependent responses were reflected in decreased performance (drift rates, accuracy)during sad trials. The detection rate (probability of making a correct response) during 8.3 ms was 12.2 % and slightly above chance level (33.333 % for three response options) during 16.7 ms trials (36.8 %). The experiments suggest a presentation time of 16.7 ms as optimal for subconscious priming. An emotion-specific response was detected during 16.7 ms while the performanceindicates a subconscious processing.