Basophil activation test is a complementary tool in the diagnosis of immediate reactions to platinum salts and taxanes.

BACKGROUND: Delabelling pathways offer confirmatory diagnosis and can prevent unnecessary second-line therapies or drug desensitization procedures after chemotherapeutic hypersensitivity reactions (CHT-HSRs). However, these pathways rely on risky in vivo tests. Data on whether in vitro tests could be helpful are scarce. We assessed the role of basophil activation test (BAT) in the diagnosis of HSRs to platin salts (PSs) and taxanes (TXs) in a well-defined population featuring varied endophenotypes and severities of HSRs. METHODS: We conducted a 3-year-long multicentric, prospective study with 121 suspected-immediate CHT-HSR patients. The allergy workup included clinical history (initial reaction based on Type I, cytokine release syndrome, and mixed phenotype's symptoms and if unable to fit in any of these, as "indeterminate"), skin testing (ST), and drug provocation testing (DPT), provided risk assessment was favorable. Final diagnosis classified patients as "hypersensitive," "non-hypersensitive," or "inconclusive." We performed BAT using CD63 and CD203c as activation markers in patients and controls. Patients underwent DPT regardless of BAT results to prevent bias. RESULTS: ST positivity significantly correlated with skin involvement, Type I phenotype, cancer recurrence, and lifetime exposures before reactions. DPTs were negative in all indeterminate phenotype patients (p = .02) and those considered low-risk, whereas they were negative in 62% moderate-risk patients. 55% were confirmed as hypersensitive (mainly Type I reactions, p < .0001), 24% as non-hypersensitive (mainly TXs and indeterminate phenotypes), and 21% as inconclusive. BAT showed 79% sensitivity in Type I IgE-mediated reactions to PSs with a high correlation to ST. CONCLUSIONS: BAT is a promising tool for delabelling and endotyping CHT-HSRs, especially Type I reactions to PSs, possibly identifying patients at risk of positive DPT. ST seems useful in confirming CHT-HSRs, especially PS-induced reactions, and DPT remains the gold standard, being essential even in moderate-risk patients.

Applications of the Microalgae Chlamydomonas and Its Bacterial Consortia in Detoxification and Bioproduction.

The wide metabolic diversity of microalgae, their fast growth rates, and low-cost production make these organisms highly promising resources for a variety of biotechnological applications, addressing critical needs in industry, agriculture, and medicine. The use of microalgae in consortia with bacteria is proving valuable in several areas of biotechnology, including the treatment of various types of wastewater, the production of biofertilizers, and the extraction of various products from their biomass. The monoculture of the microalga Chlamydomonas has been a prominent research model for many years and has been extensively used in the study of photosynthesis, sulphur and phosphorus metabolism, nitrogen metabolism, respiration, and flagellar synthesis, among others. Recent research has increasingly recognised the potential of Chlamydomonas-bacteria consortia as a biotechnological tool for various applications. The detoxification of wastewater using Chlamydomonas and its bacterial consortia offers significant potential for sustainable reduction of contaminants, while facilitating resource recovery and the valorisation of microalgal biomass. The use of Chlamydomonas and its bacterial consortia as biofertilizers can offer several benefits, such as increasing crop yields, protecting crops, maintaining soil fertility and stability, contributing to CO2 mitigation, and contributing to sustainable agricultural practises. Chlamydomonas-bacterial consortia play an important role in the production of high-value products, particularly in the production of biofuels and the enhancement of H2 production. This review aims to provide a comprehensive understanding of the potential of Chlamydomonas monoculture and its bacterial consortia to identify current applications and to propose new research and development directions to maximise their potential.

New Approaches for Basophil Activation Tests Employing Dendrimeric Antigen-Silica Nanoparticle Composites.

In vitro cell activation through specific IgE bound to high-affinity receptors on the basophil surface is a widely used strategy for the evaluation of IgE-mediated immediate hypersensitivity reactions to betalactams. Cellular activation requires drug conjugation to a protein to form a large enough structure displaying a certain distance between haptens to allow the cross-linking of two IgE antibodies bound to the basophil's surface, triggering their degranulation. However, no information about the size and composition of these conjugates is available. Routine in vitro diagnosis using the basophil activation test uses free amoxicillin, which is assumed to conjugate to a carrier present in blood. To standardize the methodology, we propose the use of well-controlled and defined nanomaterials functionalized with amoxicilloyl. Silica nanoparticles decorated with PAMAM-dendrimer-amoxicilloyl conjugates (NpDeAXO) of different sizes and amoxicilloyl densities (50-300 µmol amoxicilloyl/gram nanoparticle) have been prepared and chemically characterized. Two methods of synthesis were performed to ensure reproducibility and stability. Their functional effect on basophils was measured using an in-house basophil activation test (BAT) that determines CD63+ or CD203chigh activation markers. It was observed that NpDeAXO nanocomposites are not only able to specifically activate basophils but also do so in a more effective way than free amoxicillin, pointing to a translational potential diagnosis.

The Microalgae Chlamydomonas for Bioremediation and Bioproduct Production.

The extensive metabolic diversity of microalgae, coupled with their rapid growth rates and cost-effective production, position these organisms as highly promising resources for a wide range of biotechnological applications. These characteristics allow microalgae to address crucial needs in the agricultural, medical, and industrial sectors. Microalgae are proving to be valuable in various fields, including the remediation of diverse wastewater types, the production of biofuels and biofertilizers, and the extraction of various products from their biomass. For decades, the microalga Chlamydomonas has been widely used as a fundamental research model organism in various areas such as photosynthesis, respiration, sulfur and phosphorus metabolism, nitrogen metabolism, and flagella synthesis, among others. However, in recent years, the potential of Chlamydomonas as a biotechnological tool for bioremediation, biofertilization, biomass, and bioproducts production has been increasingly recognized. Bioremediation of wastewater using Chlamydomonas presents significant potential for sustainable reduction in contaminants and facilitates resource recovery and valorization of microalgal biomass, offering important economic benefits. Chlamydomonas has also established itself as a platform for the production of a wide variety of biotechnologically interesting products, such as different types of biofuels, and high-value-added products. The aim of this review is to achieve a comprehensive understanding of the potential of Chlamydomonas in these aspects, and to explore their interrelationship, which would offer significant environmental and biotechnological advantages.

Concepts for the Development of Person-Centered, Digitally Enabled, Artificial Intelligence-Assisted ARIA Care Pathways (ARIA 2024).

The traditional healthcare model is focused on diseases (medicine and natural science) and does not acknowledge patients' resources and abilities to be experts in their own lives based on their lived experiences. Improving healthcare safety, quality, and coordination, as well as quality of life, is an important aim in the care of patients with chronic conditions. Person-centered care needs to ensure that people's values and preferences guide clinical decisions. This paper reviews current knowledge to develop (1) digital care pathways for rhinitis and asthma multimorbidity and (2) digitally enabled, person-centered care.1 It combines all relevant research evidence, including the so-called real-world evidence, with the ultimate goal to develop digitally enabled, patient-centered care. The paper includes (1) Allergic Rhinitis and its Impact on Asthma (ARIA), a 2-decade journey, (2) Grading of Recommendations, Assessment, Development and Evaluation (GRADE), the evidence-based model of guidelines in airway diseases, (3) mHealth impact on airway diseases, (4) From guidelines to digital care pathways, (5) Embedding Planetary Health, (6) Novel classification of rhinitis and asthma, (7) Embedding real-life data with population-based studies, (8) The ARIA-EAACI (European Academy of Allergy and Clinical Immunology) strategy for the management of airway diseases using digital biomarkers, (9) Artificial intelligence, (10) The development of digitally enabled, ARIA person-centered care, and (11) The political agenda. The ultimate goal is to propose ARIA 2024 guidelines centered around the patient to make them more applicable and sustainable.

Digitally-enabled, person-centred care (PCC) in allergen immunotherapy: An ARIA-EAACI Position Paper.

In rhinitis and asthma, several mHealth apps have been developed but only a few have been validated. However, these apps have a high potential for improving person-centred care (PCC), especially in allergen immunotherapy (AIT). They can provide support in AIT initiation by selecting the appropriate patient and allergen shared decision-making. They can also help in (i) the evaluation of (early) efficacy, (ii) early and late stopping rules and (iii) the evaluation of (carried-over) efficacy after cessation of the treatment course. Future perspectives have been formulated in the first report of a joint task force (TF)-Allergic Rhinitis and Its Impact on Asthma (ARIA) and the European Academy of Allergy and Clinical Immunology (EAACI)-on digital biomarkers. The TF on AIT now aims to (i) outline the potential of the clinical applications of mHealth solutions, (ii) express their current limitations, (iii) make proposals regarding further developments for both clinical practice and scientific purpose and (iv) suggest which of the tools might best comply with the purpose of digitally-enabled PCC in AIT.

Working with companies that manufacture breastmilk substitutes: An EAACI position paper.

Breastmilk is the optimal source of nutrition for infants and should ideally be provided exclusively for the first 6 months of life, and alongside complementary food until 2 years of life. However, there are circumstances where a breastmilk substitute (BMS) may be required. This includes maternal and/or child conditions or personal preference. Whilst these circumstances should never be used as an opportunity to promote BMS, healthcare professionals (HCPs) need to have the knowledge of suitable alternatives and should always be guided by scientific and health motives when recommending a BMS. The Task Force 'Milk Formula Industry Sponsorship' from the European Academy of Allergy and Clinical Immunology (EAACI), provides with this publication recommendations for EAACI interactions with the BMS manufacturers and how this will be supervised.

High-dose atorvastatin therapy progressively decreases skeletal muscle mitochondrial respiratory capacity in humans.

BACKGROUNDWhile the benefits of statin therapy on atherosclerotic cardiovascular disease are clear, patients often experience mild to moderate skeletal myopathic symptoms, the mechanism for which is unknown. This study investigated the potential effect of high-dose atorvastatin therapy on skeletal muscle mitochondrial function and whole-body aerobic capacity in humans.METHODSEight overweight (BMI, 31.9 ± 2.0) but otherwise healthy sedentary adults (4 females, 4 males) were studied before (day 0) and 14, 28, and 56 days after initiating atorvastatin (80 mg/d) therapy.RESULTSMaximal ADP-stimulated respiration, measured in permeabilized fiber bundles from muscle biopsies taken at each time point, declined gradually over the course of atorvastatin treatment, resulting in > 30% loss of skeletal muscle mitochondrial oxidative phosphorylation capacity by day 56. Indices of in vivo muscle oxidative capacity (via near-infrared spectroscopy) decreased by 23% to 45%. In whole muscle homogenates from day 0 biopsies, atorvastatin inhibited complex III activity at midmicromolar concentrations, whereas complex IV activity was inhibited at low nanomolar concentrations.CONCLUSIONThese findings demonstrate that high-dose atorvastatin treatment elicits a striking progressive decline in skeletal muscle mitochondrial respiratory capacity, highlighting the need for longer-term dose-response studies in different patient populations to thoroughly define the effect of statin therapy on skeletal muscle health.FUNDINGNIH R01 AR071263.

Necessary Role of Ceramides in the Human Microvascular Endothelium During Health and Disease.

BACKGROUND: Elevated plasma ceramides and microvascular dysfunction both independently predict adverse cardiac events. Despite the known detrimental effects of ceramide on the microvasculature, evidence suggests that activation of the shear-sensitive, ceramide-forming enzyme NSmase (neutral sphingomyelinase) elicits formation of vasoprotective nitric oxide (NO). Here, we explore a novel hypothesis that acute ceramide formation through NSmase is necessary for maintaining NO signaling within the human microvascular endothelium. We further define the mechanism through which ceramide exerts beneficial effects and discern key mechanistic differences between arterioles from otherwise healthy adults (non-coronary artery disease [CAD]) and patients diagnosed with CAD. METHODS: Human arterioles were dissected from discarded surgical adipose tissue (n=166), and vascular reactivity to flow and C2-ceramide was assessed. Shear-induced NO and mitochondrial hydrogen peroxide (H2O2) production were measured in arterioles using fluorescence microscopy. H2O2 fluorescence was assessed in isolated human umbilical vein endothelial cells. RESULTS: Inhibition of NSmase in arterioles from otherwise healthy adults induced a switch from NO to NOX-2 (NADPH-oxidase 2)-dependent H2O2-mediated flow-induced dilation. Endothelial dysfunction was prevented by treatment with sphingosine-1-phosphate (S1P) and partially prevented by C2-ceramide and an agonist of S1P-receptor 1 (S1PR1); the inhibition of the S1P/S1PR1 signaling axis induced endothelial dysfunction via NOX-2. Ceramide increased NO production in arterioles from non-CAD adults, an effect that was diminished with inhibition of S1P/S1PR1/S1P-receptor 3 signaling. In arterioles from patients with CAD, inhibition of NSmase impaired the overall ability to induce mitochondrial H2O2 production and subsequently dilate to flow, an effect not restored with exogenous S1P. Acute ceramide administration to arterioles from patients with CAD promoted H2O2 as opposed to NO production, an effect dependent on S1P-receptor 3 signaling. CONCLUSION: These data suggest that despite differential downstream signaling between health and disease, NSmase-mediated ceramide formation is necessary for proper functioning of the human microvascular endothelium. Therapeutic strategies that aim to significantly lower ceramide formation may prove detrimental to the microvasculature.

Hypersensitivity reactions to proton pump inhibitors. An EAACI position paper.

Proton pump inhibitors (PPIs) are invaluable therapeutic options in a variety of dyspeptic diseases. In addition to their well-known risk profile, PPI consumption is related to food and environmental allergies, dysbiosis, osteoporosis, as well as immediate and delayed hypersensitivity reactions (HSRs). The latter, although a rare event, around 1%-3%, due to the extraordinarily high rate of prescription and consumption of PPIs are related to a substantial risk. In this Position Paper, we provide clinicians with practical evidence-based recommendations for the diagnosis and management of HSRs to PPIs. Furthermore, the unmet needs proposed in the document aim to stimulate more in-depth investigations in the topic.

Biomarkers of immediate drug hypersensitivity.

Immediate drug hypersensitivity reactions (IDHRs) are a burden for patients and the health systems. This problem increases when taking into account that only a small proportion of patients initially labelled as allergic are finally confirmed after an allergological workup. The diverse nature of drugs involved will imply different interactions with the immunological system. Therefore, IDHRs can be produced by a wide array of mechanisms mediated by the drug interaction with specific antibodies or directly on effector target cells. These heterogeneous mechanisms imply an enhanced complexity for an accurate diagnosis and the identification of the phenotype and endotype at early stages of the reaction is of vital importance. Currently, several endophenotypic categories (type I IgE/non-IgE, cytokine release, Mast-related G-protein coupled receptor X2 (MRGPRX2) or Cyclooxygenase-1 (COX-1) inhibition and their associated biomarkers have been proposed. A precise knowledge of endotypes will permit to discriminate patients within the same phenotype, which is crucial in order to personalise diagnosis, future treatment and prevention to improve the patient's quality of life.

The copper-responsive regulator CsoR is indirectly involved in Bradyrhizobium diazoefficiens denitrification.

The soybean endosymbiont Bradyrhizobium diazoefficiens harbours the complete denitrification pathway that is catalysed by a periplasmic nitrate reductase (Nap), a copper (Cu)-containing nitrite reductase (NirK), a c-type nitric oxide reductase (cNor), and a nitrous oxide reductase (Nos), encoded by the napEDABC, nirK, norCBQD, and nosRZDFYLX genes, respectively. Induction of denitrification genes requires low oxygen and nitric oxide, both signals integrated into a complex regulatory network comprised by two interconnected cascades, FixLJ-FixK2-NnrR and RegSR-NifA. Copper is a cofactor of NirK and Nos, but it has also a role in denitrification gene expression and protein synthesis. In fact, Cu limitation triggers a substantial down-regulation of nirK, norCBQD, and nosRZDFYLX gene expression under denitrifying conditions. Bradyrhizobium diazoefficiens genome possesses a gene predicted to encode a Cu-responsive repressor of the CsoR family, which is located adjacent to copA, a gene encoding a putative Cu+-ATPase transporter. To investigate the role of CsoR in the control of denitrification gene expression in response to Cu, a csoR deletion mutant was constructed in this work. Mutation of csoR did not affect the capacity of B. diazoefficiens to grow under denitrifying conditions. However, by using qRT-PCR analyses, we showed that nirK and norCBQD expression was much lower in the csoR mutant compared to wild-type levels under Cu-limiting denitrifying conditions. On the contrary, copA expression was significantly increased in the csoR mutant. The results obtained suggest that CsoR acts as a repressor of copA. Under Cu limitation, CsoR has also an indirect role in the expression of nirK and norCBQD genes.

Necessary Role of Acute Ceramide Formation in The Human Microvascular Endothelium During Health and Disease.

Background: Elevated plasma ceramides independently predict adverse cardiac events and we have previously shown that exposure to exogenous ceramide induces microvascular endothelial dysfunction in arterioles from otherwise healthy adults (0-1 risk factors for heart disease). However, evidence also suggests that activation of the shear-sensitive, ceramide forming enzyme neutral sphingomyelinase (NSmase) enhances vasoprotective nitric oxide (NO) production. Here we explore a novel hypothesis that acute ceramide formation through NSmase is necessary for maintaining NO signaling within the human microvascular endothelium. We further define the mechanism through which ceramide exerts beneficial effects and discern key mechanistic differences between arterioles from otherwise healthy adults and patients with coronary artery disease (CAD). Methods: Human arterioles were dissected from otherwise discarded surgical adipose tissue (n=123), and vascular reactivity to flow and C2-ceramide was assessed. Shear-induced NO production was measured in arterioles using fluorescence microscopy. Hydrogen peroxide (H2O2) fluorescence was assessed in isolated human umbilical vein endothelial cells. Results: Inhibition of NSmase in arterioles from otherwise healthy adults induced a switch from NO to H2O2-mediated flow-induced dilation within 30 minutes. In endothelial cells, NSmase inhibition acutely increased H2O2 production. Endothelial dysfunction in both models was prevented by treatment with C2-ceramide, S1P, and an agonist of S1P-receptor 1 (S1PR1), while the inhibition of S1P/S1PR1 signaling axis induced endothelial dysfunction. Ceramide increased NO production in arterioles from healthy adults, an effect that was diminished with inhibition of S1P/S1PR1/S1PR3 signaling. In arterioles from patients with CAD, inhibition of NSmase impaired dilation to flow. This effect was not restored with exogenous S1P. Although, inhibition of S1P/S1PR3 signaling impaired normal dilation to flow. Acute ceramide administration to arterioles from patients with CAD also promoted H2O2 as opposed to NO production, an effect dependent on S1PR3 signaling. Conclusion: These data suggest that despite key differences in downstream signaling between health and disease, acute NSmase-mediated ceramide formation and its subsequent conversion to S1P is necessary for proper functioning of the human microvascular endothelium. As such, therapeutic strategies that aim to significantly lower ceramide formation may prove detrimental to the microvasculature.

A synthetic glycodendropeptide induces methylation changes on regulatory T cells linked to tolerant responses in anaphylactic-mice.

Introduction: Lipid transfer proteins (LTPs) are allergens found in a wide range of plant-foods. Specifically, Pru p 3, the major allergen of peach, is commonly responsible for severe allergic reactions. The need for new alternatives to conventional food allergy treatments, like restrictive diets, suggests allergen immunotherapy as a promising option. It has been demonstrated that sublingual immunotherapy (SLIT) with synthetic glycodendropeptides, such as D1ManPrup3, containing mannose and Pru p 3 peptides induced tolerance in mice and that the persistence of this effect depends on treatment dose (2nM or 5nM). Moreover, it produces changes associated with differential gene expression and methylation profile of dendritic cells, as well as phenotypical changes in regulatory T cells (Treg). However, there are no works addressing the study of epigenetic changes in terms of methylation in the cell subsets that sustain tolerant responses, Treg. Therefore, in this work, DNA methylation changes in splenic-Treg from Pru p 3 anaphylactic mice were evaluated. Methods: It was performed by whole genome bisulphite sequencing comparing SLIT-D1ManPrup3 treated mice: tolerant (2nM D1ManPrup3), desensitized (5nM D1ManPrup3), and sensitized but not treated (antigen-only), with anaphylactic mice. Results: Most of the methylation changes were found in the gene promoters from both SLIT-treated groups, desensitized (1,580) and tolerant (1,576), followed by the antigen-only (1,151) group. Although tolerant and desensitized mice showed a similar number of methylation changes, only 445 genes were shared in both. Remarkably, interesting methylation changes were observed on the promoter regions of critical transcription factors for Treg function like Stat4, Stat5a, Stat5b, Foxp3, and Gata3. In fact, Foxp3 was observed exclusively as hypomethylated in tolerant group, whereas Gata3 was only hypomethylated in the desensitized mice. Discussion: In conclusion, diverse D1ManPrup3 doses induce different responses (tolerance or desensitization) in mice, which are reflected by differential methylation changes in Tregs.

The One Health approach for allergic diseases and asthma.

The One Health approach is a collaborative and interdisciplinary strategy with focal point on human, animal, and environmental health interconnections. One Health can support the advanced management of allergic diseases and asthma, as complex, multifactorial diseases driven by interactions between the resilience response to the exposome. According to the One Health concept allergic diseases and asthma arising from exposures to a wide range of allergens, infectious agents and irritants (such as pollutants) occurring indoors and outdoors can be heavily influenced by environmental health (air, water, and soil quality) intermingled with animal health. These are currently heavily impacted by climate change, land use, urbanization, migration, overpopulation, and many more. Thus, a coordinated response to address the underlying factors that contribute to the development of allergic diseases and asthma needs to focus on the environment, human, and animal health altogether. Collaborative efforts across multiple sectors, including public health, veterinary medicine, environmental science, and community engagement are thus needed. A wide range of activities, including monitoring and surveillance of environmental and health data, targeted interventions to reduce exposures to allergens and irritants, and research on the underlying mechanisms that drive the development of allergic diseases and asthma are needed to move the field forward. In this consensus document elaborated by the European Academy of Allergy and Clinical Immunology (EAACI) and American Academy of Allergy, Asthma, and Immunology (AAAAI) under the practical allergy (PRACTALL) series, we provide insights into the One Heath approach aiming to provide a framework for addressing the complex and multifactorial nature of allergic diseases and asthma.

Current status of pancreatic cancer with oligometastasis.

BACKGROUND: Pancreatic cancer is the seventh leading cause of death worldwide, with ductal adenocarcinoma as the most frequent neoplasm. Half of the patients who are diagnosed have metastases at the time of diagnosis. OBJECTIVE: A review of the treatment of resectable pancreatic adenocarcinoma with oligometastatic disease was carried out in order to present an overview of the existing evidence. METHOD: A bibliographic search was carried in PubMed/Medline, Clinical Key and Index Medicus vhith MESH terms, from the year 1993 to 2022. RESULTS: Patients with liver or lung metastases due to pancreatic ductal adenocarcinoma who undergo surgery and chemotherapy have a longer survival in carefully selected patients. CONCLUSIONS: The evidence regarding surgery in patients with pancreatic ductal adenocarcinoma and oligometastasis is limited and further randomized controlled trials are needed for both scenarios. As well as established criteria that help the selection of patients who can receive this type of treatment.

ANTECEDENTES: El cáncer pancreático es la séptima causa de muerte en el mundo, siendo el adenocarcinoma ductal del páncreas la neoplasia más frecuente. La mitad de los pacientes que son diagnosticados presentan metástasis al momento del diagnóstico. OBJETIVO: Se realizó una revisión sobre el tratamiento del adenocarcinoma pancreático resecable con enfermedad oligometastásica con el fin de presentar un panorama sobre la evidencia existente. MÉTODO: Se realizó una búsqueda bibliográfica en PubMed/Medline, Clinical Key e Index Medicus con términos MESH desde 1993 hasta 2022. RESULTADOS: Los pacientes con metástasis hepáticas o pulmonares por adenocarcinoma ductal de páncreas que son sometidos a cirugía y quimioterapia tienen una mayor sobrevida en casos cuidadosamente seleccionados. CONCLUSIONES: La evidencia respecto a la cirugía en pacientes con adenocarcinoma ductal de páncreas y oligometástasis es limitada y se necesitan ensayos controlados aleatorizados adicionales para ambos escenarios, así como criterios bien establecidos que ayuden a la selección de los pacientes que pueden recibir este tipo de tratamiento.

Influence of Pore Size in Protein G'-Grafted Mesoporous Silica Nanoparticles as a Serum Pretreatment System for In Vitro Allergy Diagnosis.

Particles with the capacity to bind to immunoglobulin G (IgG) can be used for the purification of IgG or to process clinical samples for diagnostic purposes. For in vitro allergy diagnosis, the high IgG levels in serum can interfere with the detection of allergen-specific IgE, the main diagnostic biomarker. Although commercially available, current materials present a low IgG capture capacity at large IgG concentrations or require complex protocols, preventing their use in the clinic. In this work, mesoporous silica nanoparticles are prepared with different pore sizes, to which IgG-binding protein G' is grafted. It is found that for one particular optimal pore size, the IgG capture capacity of the material is greatly enhanced. The capacity of this material to efficiently capture human IgG in a selective way (compared to IgE) is demonstrated in both solutions of known IgG concentrations as well as in complex samples, like serum, from healthy controls and allergic patients using a simple and fast incubation protocol. Interestingly, IgG removal using the best-performing material enhances in vitro IgE detection in sera from patients allergic to amoxicillin. These results highlight the great translation potential of this strategy to the clinic in the context of in vitro allergy diagnosis.

Co-exposure to pathogens in wild ungulates from Doñana National Park, South Spain.

Multiple infections or co-exposure to pathogens should be considered systematically in wildlife to better understand the ecology and evolution of host-pathogen relationships, so as to better determine the potential use of multiple pathogens as indicators to guide health management. We describe the pattern of co-exposure to several pathogens (i.e. simultaneous positive diagnosis to pathogens in an individual considering Mycobacterium tuberculosis complex lesions, and the presence of antibodies against Toxoplasma gondii, bluetongue virus, and hepatitis E virus) and assessed their main drivers in the wild ungulate community from Doñana National Park (red deer, fallow deer, and wild boar) for a 13-years longitudinal study. The lower-than-expected frequency of co-exposure registered in all species was consistent with non-mutually exclusive hypotheses (e.g. antagonism or disease-related mortality), which requires further investigation. The habitat generalist species (red deer and wild boar) were exposed to a greater diversity of pathogens (frequency of co-exposure around 50%) and/or risk factors than fallow deer (25.0% ± CI95% 4.9). Positive relationships between pathogens were evidenced, which may be explained by common risk factors favouring exposure. The specific combination of pathogens in individuals was mainly driven by different groups of factors (individual, environmental, stochastic, and populational), as well as its interaction, defining a complex eco-epidemiological landscape. To deepen into the main determinants and consequences of co-infections in a complex assemblage of wild hosts, and at the interface with humans and livestock, there also is needed to expand the range of pathogens and compare diverse assemblages of hosts under different environmental and management circumstances.