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Microplastics (MPs) are distributed throughout the world oceans and represent one of the greatest environmental concerns of marine pollution. In the Gulf of Cadiz (GoC), MPs are found throughout the water column, on the seafloor, and accumulated within commercial marine species, primarily due to discharges from the main estuaries. The aim of this study was to analyse the transport pathways, spatial distribution, and accumulation regions of MPs in the GoC based on their density and source. For this, a Lagrangian transport model was coupled to a high-resolution hydrodynamic model and four particle sources were considered: Cape San Vicente, Guadiana Estuary, Guadalquivir Estuary, and Bay of Cadiz/Guadalete River. To account for the diversity of plastics detected in the GoC, particles with ten different densities were used, from low-density to high-density polymers. This study indicates that a significant proportion of low-density MPs accumulate near their sources and within the top few centimetres of the water column due to local surface currents. The Guadalquivir and Guadiana estuaries are the primary contributors to the high accumulation of low-density MPs on the GoC eastern shelf, consistent with previous field studies identifying these estuaries as the main sources of MPs into the region, including polyethylene and polypropylene. In contrast, the Bay of Cadiz/Guadalete River seems to be the primary source of low-density MPs in offshore waters within the uppermost meter of the water column, influenced by local mesoscale features. The Guadalquivir Estuary seems to be the main source of high-density MPs into the continental shelves, such as polystyrene, polyamide, and polyvinyl chloride, followed by the Bay of Cadiz/Guadalete River, and to a lesser extent, the Guadiana estuary. These MPs accumulate near their sources at depths of 3.5 to 50 m due to their high sinking rates, but can also be transported offshore by deep currents, either northwards along the Portuguese offshore waters or westwards off the GoC offshore region., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Allergen immunotherapy is highly effective for seasonal pollinosis. Three years of treatment results in long-term efficacy. This disease modification is accompanied by downregulation of allergen-specific Th2 responses and the induction of persistent specific IgG- and IgA-associated IgE-blocking activity. In children with seasonal rhinitis, both subcutaneous and sublingual pollen immunotherapy have been shown to reduce the development of asthma symptoms and asthma medication requirements. House dust mite tablet allergen immunotherapy has been shown to be effective for perennial mite-driven rhinitis in adults and children and may suppress asthma exacerbations, whereas its long-term efficacy has yet to be explored. The success of primary prevention of peanut allergy in childhood by introduction of peanut into the diet during infancy provides a strong rationale to explore whether primary prevention of inhalant allergies and asthma may also be possible. House dust mite allergy is a major risk factor for developing asthma. Preliminary data in at-risk children suggest that sublingual house dust mite immunotherapy initiated during infancy could reduce the onset of multiple allergen sensitizations and prevent the development of asthma at age 6 years. This possibility should now be explored in an adequately powered, prospectively randomized controlled trial., (Copyright © 2023. Published by Elsevier Inc.)

This study presents an analysis of the impacts of the changes in bottom depth along the Guadalquivir Estuary on tidal dynamics. A realistic non-linear 1D numerical model, incorporating changes in both breadth and bottom depth, was employed to investigate the involved effects. The findings reveal a significant amplification of the M2 tidal wave towards the upper region of the Estuary, resulting from the gradual deepening caused by multiple dredging operations. The Estuary exhibits a pronounced tendency towards resonance, which is further enhanced by its deepening, resulting in reduced bottom friction and a smaller decrease in tidal wave amplitude as it propagates through the Estuary. The alterations in depth, particularly in breadth, along the Estuary play a crucial role in determining the magnitude of the resonant response of the M 2 tidal wave., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Allergen immunotherapy (AIT) is a well-established disease-modifying therapy for allergic rhinitis, yet the fundamental mechanisms underlying its clinical effect remain inadequately understood. Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy was a randomized, double-blind, placebo-controlled trial of individuals allergic to timothy grass who received 2 years of placebo (n = 30), subcutaneous immunotherapy (SCIT) (n = 27), or sublingual immunotherapy (SLIT) (n = 27) and were then followed for 1 additional year., Objective: We used yearly biospecimens from the Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy study to identify molecular mechanisms of response., Methods: We used longitudinal transcriptomic profiling of nasal brush and PBMC samples after allergen provocation to uncover airway and systemic expression pathways mediating responsiveness to AIT., Trial Registration: ClinicalTrials.gov Identifier: NCT01335139, EudraCT Number: 2010-023536-16., Results: SCIT and SLIT demonstrated similar changes in gene module expression over time. In nasal samples, alterations included downregulation of pathways of mucus hypersecretion, leukocyte migration/activation, and endoplasmic reticulum stress (log2 fold changes -0.133 to -0.640, false discovery rates [FDRs] <0.05). We observed upregulation of modules related to epithelial development, junction formation, and lipid metabolism (log2 fold changes 0.104 to 0.393, FDRs <0.05). In PBMCs, modules related to cellular stress response and type 2 cytokine signaling were reduced by immunotherapy (log2 fold changes -0.611 to -0.828, FDRs <0.05). Expression of these modules was also significantly associated with both Total Nasal Symptom Score and peak nasal inspiratory flow, indicating important links between treatment, module expression, and allergen response., Conclusions: Our results identify specific molecular responses of the nasal airway impacting barrier function, leukocyte migration activation, and mucus secretion that are affected by both SCIT and SLIT, offering potential targets to guide novel strategies for AIT., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

This study was conducted to address the changes in the surface distribution of trace metals (cobalt, copper, iron, cadmium, nickel, zinc, lead and molybdenum) as they are advected from the Gulf of Cadiz to the Alboran Sea, through the Strait of Gibraltar (south Iberian Peninsula), regions of great ecosystemic importance. Trace metals concentrations were measured in samples collected during two oceanographic cruises, together with the main factors affecting their spatial distribution and temporal variability (i.e., wind and surface currents). Several rivers, the main source of trace metals in this region, flow into the Gulf of Cadiz which is connected with the Alboran Sea through the Strait of Gibraltar by the general circulation pattern. The surface circulation pattern leads to an offshore-eastward gradient that is highly influenced by wind variability. An increase in vertical turbulence induced by the winds or the tidal cycle causes the dilution of trace metals' concentration by mixing rich-metal superficial waters with poor-metal subsurface waters. Additionally, along the eastward displacement of surface waters, several water retention zones have been described (Trafalgar, Camarinal, the Coastal Cyclonic Gyre) that imply an increase in trace metals concentration close to the coast. In addition, our results suggest that the coastal edges of the Strait of Gibraltar also act as a source of certain metals to the Alboran Sea, probably due to the industries in the proximity areas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Allergen immunotherapy is highly effective in selected patients with allergic rhinitis, allergic asthma, and Hymenoptera venom allergy. Unlike anti-allergic drugs, both subcutaneous and sublingual immunotherapies have been shown to modify the underlying cause of the disease, with proved long-term clinical benefits after treatment cessation. In this review, we analyzed 10 randomized, double-blind, placebo controlled clinical trials of allergen immunotherapy that included blinded follow-up for at least 1 year after treatment withdrawal. Three studies of pollen subcutaneous immunotherapy provided evidence that a sustained, tolerogenic effect of subcutaneous immunotherapy can be achieved after 3 years of treatment. Six trials of sublingual immunotherapy provided robust evidence for long-term clinical benefit and persistent immunologic changes after grass pollen, house-dust mite, or Japanese cedar immunotherapy, whereas a clinical trial of both sublingual and subcutaneous grass pollen immunotherapies showed that 2 years of immunotherapy were efficacious but insufficient to induce long-term tolerance. These studies strongly supported international guidelines that recommend at least 3 years of allergen immunotherapy of proven value to achieve disease modification and sustained clinical and immunologic tolerance.

Allergen immunotherapy is effective for the treatment of allergic rhinitis, allergic asthma, and Hymenoptera venom allergy. In view of potential side effects, cost, and the necessary patient commitment, an important question is whether allergen immunotherapy provides persistent clinical benefits after treatment discontinuation. Here, we appraise the existing evidence for long-term effects of both subcutaneous and sublingual immunotherapy in terms of clinical efficacy, immune mechanisms, prevention of asthma development, and prevention of new allergen sensitizations. Evidence from large, randomized, double-blind, placebo-controlled clinical trials that include a follow-up phase after treatment cessation demonstrate long-term efficacy. The data strongly support recommendations in international guidelines that both sublingual and subcutaneous immunotherapy should be continued for a minimum of 3 years to achieve disease modification and long-term tolerance. Grass pollen immunotherapy for seasonal rhinitis may inhibit the onset of asthma symptoms and requirements for asthma medication. Whether early intervention in infancy with mite sublingual immunotherapy may prevent asthma remains to be tested., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

A catchment model for river basins and a hydrodynamic model were combined in order to simulate the spreading of the turbidity plume produced by sediment discharges from the Guadalquivir River basin within the Gulf of Cádiz under different meteorological conditions. The current fields provided by the hydrodynamic model and a transport-diffusion scheme based on tracking virtual particles tracking released at the river mouth have enabled us to simulate turbidity plumes that show great similarity with the plumes observed in satellite images. The most relevant results of the study show that in the absence of winds, the plume tends to spread very slowly, gradually progressing northwards; this is because of the symmetry between the filling and draining flows at the mouth of the Guadalquivir and low intensity of the tidal currents beyond the mouth. In addition, the transport of the plume towards the Strait of Gibraltar requires wind conditions with a northerly, north-westerly or westerly component. Westwards transport, however, requires winds with an easterly, southerly, or south-easterly component. The periods of heaviest rainfall in the Guadalquivir River basin coincide with winds mainly from the west; therefore, the times of maximum discharge at the mouth of the river occur when there are wind conditions that favour the transport of the matter suspended in the plume, southwards along the coast, towards the Strait of Gibraltar and the Alboran Sea. Linking the watershed catchment and hydrodynamic models has proved its suitability to predict the evolution and reaching of the sediment plumes from the Guadalquivir River discharges and the experience encourages the use of that methodology to be applied in a future prediction system for the creation and evolution of those sediment plumes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Long-term efficacy that occurs with allergen immunotherapy of proven value is associated with decreases in IgE-dependent activation of mast cells and tissue eosinophilia. This suppression of type 2 immunity is accompanied by early induction of regulatory T cells, immune deviation in favor of T H 1 responses, and induction of local and systemic IgG, IgG 4 , and IgA antibodies. These "protective" antibodies can inhibit allergen-IgE complex formation and consequent mast cell triggering and IgE-facilitated T H 2-cell activation. Recent studies have highlighted the importance of innate responses mediated by type 2 dendritic cells and innate lymphoid cells in allergic inflammation. These cell types are under the regulation of cytokines such as thymic stromal lymphopoietin and IL-33 derived from the respiratory epithelium. Novel subsets of regulatory cells induced by immunotherapy include IL-35-producing regulatory T cells, regulatory B cells, a subset of T follicular regulatory cells, and IL-10-producing group 2 innate lymphoid cells. These mechanisms point to biomarkers that require testing for their ability to predict clinical response to immunotherapy and to inform novel approaches for better efficacy, safety, and long-term tolerance., (Copyright © 2021. Published by Elsevier Inc.)

Polyunsaturated aldehydes (PUAs) are bioactive molecules suggested as chemical defenses and infochemicals. In marine coastal habitats, diatoms reach high PUA production levels during bloom episodes. Two fractions of PUA can usually be analyzed: pPUA obtained via artificial breakage of collected phytoplankton cells and dissolved PUA already released to the environment (dPUA). In nature, resource supply arises as a main environmental controlling factor of PUA production. In this work, we monitored the vertical distribution and daily variation of pPUA associated with large-size phytoplankton and dPUA, at three sites located in the Alborán Sea from mesotrophic to oligotrophic waters. The results corroborate the presence of large-size PUA producers in oligotrophic and mesotrophic waters with a significant (58%-85%) diatom biomass. In addition to diatoms, significant correlations between pPUA production and dinoflagellate and silicoflagellate abundance were observed. 2 E ,4 E / Z -Heptadienal was the most abundant aldehyde at the three sites with higher values (17.1 fg·cell -1 ) at the most oligotrophic site. 2 E ,4 E /Z-Decadienal was the least abundant aldehyde, decreasing toward the oligotrophic site. For the first time, we describe the daily fluctuation of pPUA attributable to cellular physiological state and not exclusively to taxonomical composition. Our results demonstrate the persistence of threshold levels of dPUA deep in the water column, as well as the different chromatographic profiles of dPUA compared with pPUA. We propose different isomerization processes that alter the chemical structure of the released PUAs with unknown effects on their stability, biological function, and potential bioactivity.