Impact of the COVID-19 Health Crisis on Trans Women and Cis Men Sex Workers in Spain.

The objective of the study was to describe the impact of the COVID-19 pandemic on sex workers in accessing health and social services. A qualitative study was conducted using semi-structured interviews with 29 participants in Barcelona, Spain. Data were analyzed using thematic analysis. Four themes were identified: (1) impact of COVID-19 on physical/mental health, (2) barriers and facilitators to health/social service access, (3) health decision-making, and (4) suggestions for future pandemic situations. Barriers to accessing health services were structural. Non-governmental organization support was the main facilitating factor. A person-centered, intersectional approach is suggested for future practice, considering co-occurring syndemic factors.

miR-124 as a Liquid Biopsy Prognostic Biomarker in Small Extracellular Vesicles from NSCLC Patients.

Despite advances in non-small cell lung cancer (NSCLC) research, this is still the most common cancer type that has been diagnosed up to date. microRNAs have emerged as useful clinical biomarkers in both tissue and liquid biopsy. However, there are no reliable predictive biomarkers for clinical use. We evaluated the preclinical use of seven candidate miRNAs previously identified by our group. We collected a total of 120 prospective samples from 88 NSCLC patients. miRNA levels were analyzed via qRT-PCR from tissue and blood samples. miR-124 gene target prediction was performed using RNA sequencing data from our group and interrogating data from 2952 NSCLC patients from two public databases. We found higher levels of all seven miRNAs in tissue compared to plasma samples, except for miR-124. Our findings indicate that levels of miR-124, both free-circulating and within exosomes, are increased throughout the progression of the disease, suggesting its potential as a marker of disease progression in both advanced and early stages. Our bioinformatics approach identified KPNA4 and SPOCK1 as potential miR-124 targets in NSCLC. miR-124 levels can be used to identify early-stage NSCLC patients at higher risk of relapse.

Prognostic Impact of Dihydropyrimidine Dehydrogenase Germline Variants in Unresectable Non-Small Cell Lung Cancer Patients Treated with Platin-Based Chemotherapy.

Platin-based chemotherapy is the standard treatment for patients with non-small cell lung cancer (NSCLC). However, resistance to this therapy is a major obstacle in successful treatment. In this study, we aimed to investigate the impact of several pharmacogenetic variants in patients with unresectable NSCLC treated with platin-based chemotherapy. Our results showed that DPYD variant carriers had significantly shorter progression-free survival and overall survival compared to DPYD wild-type patients, whereas DPD deficiency was not associated with a higher incidence of high-grade toxicity. For the first time, our study provides evidence that DPYD gene variants are associated with resistance to platin-based chemotherapy in NSCLC patients. Although further studies are needed to confirm these findings and explore the underlying mechanisms of this association, our results suggest that genetic testing of DPYD variants may be useful for identifying patients at a higher risk of platin-based chemotherapy resistance and might be helpful in guiding future personalized treatment strategies in NSCLC patients.

Strategic roadmap to assess forest vulnerability under air pollution and climate change.

Although it is an integral part of global change, most of the research addressing the effects of climate change on forests have overlooked the role of environmental pollution. Similarly, most studies investigating the effects of air pollutants on forests have generally neglected the impacts of climate change. We review the current knowledge on combined air pollution and climate change effects on global forest ecosystems and identify several key research priorities as a roadmap for the future. Specifically, we recommend (1) the establishment of much denser array of monitoring sites, particularly in the South Hemisphere; (2) further integration of ground and satellite monitoring; (3) generation of flux-based standards and critical levels taking into account the sensitivity of dominant forest tree species; (4) long-term monitoring of N, S, P cycles and base cations deposition together at global scale; (5) intensification of experimental studies, addressing the combined effects of different abiotic factors on forests by assuring a better representation of taxonomic and functional diversity across the ~73,000 tree species on Earth; (6) more experimental focus on phenomics and genomics; (7) improved knowledge on key processes regulating the dynamics of radionuclides in forest systems; and (8) development of models integrating air pollution and climate change data from long-term monitoring programs.

Four Cholesterol-Recognition Motifs in the Pore-Forming and Translocation Domains of Adenylate Cyclase Toxin Are Essential for Invasion of Eukaryotic Cells and Lysis of Erythrocytes.

Adenylate Cyclase Toxin (ACT or CyaA) is one of the important virulence factors secreted by Bordetella pertussis, the bacterium causative of whooping cough. ACT debilitates host defenses by production of unregulated levels of cAMP into the cell cytosol upon delivery of its N-terminal domain with adenylate cyclase activity (AC domain) and by forming pores in the plasma membrane of macrophages. Binding of soluble toxin monomers to the plasma membrane of target cells and conversion into membrane-integrated proteins are the first and last step for these toxin activities; however, the molecular determinants in the protein or the target membrane that govern this conversion to an active toxin form are fully unknown. It was previously reported that cytotoxic and cytolytic activities of ACT depend on membrane cholesterol. Here we show that ACT specifically interacts with membrane cholesterol, and find in two membrane-interacting ACT domains, four cholesterol-binding motifs that are essential for AC domain translocation and lytic activities. We hypothesize that direct ACT interaction with membrane cholesterol through those four cholesterol-binding motifs drives insertion and stabilizes the transmembrane topology of several helical elements that ultimately build the ACT structure for AC delivery and pore-formation, thereby explaining the cholesterol-dependence of the ACT activities. The requirement for lipid-mediated stabilization of transmembrane helices appears to be a unifying mechanism to modulate toxicity in pore-forming toxins.

Analytical validation of a laboratory-development multigene pharmacogenetic assay.

OBJECTIVE: The implementation of pharmacogenetics (PGx) in clinical practice is an essential tool for personalized medicine. However, clinical laboratories must validate their procedures before being used to perform PGx studies in patients, in order to confirm that they are adequate for the intended purposes. METHODS: We designed a validation process for our in-house pharmacogenetic PCR-based method assay. RESULTS: The concordance to reference, repeatability and reproducibility was 100%. Sensitivity and specificity were 100% for the detection of variant diplotypes in CYP2C9, CYP3A5, TPMT, DPYD and UGT1A1 genes. The sensitivity was lower in the detection of CYP2C19 variants due to a limitation in the design that prevents the detection of CYP2C19 *2/*10 diplotype. CONCLUSIONS: The success of implementing clinical pharmacogenetic testing into routine clinical practice is dependent on the precision of genotyping. Limitations must be bearing in mind to guarantee the quality of PGx assays in clinical laboratory practice. We provided objective evidence that the necessary requirements in our laboratory-development assay were fulfilled.

Novel SLC12A2-ROS1 Fusion in Non-Small Cell Lung Cancer with a Significant Response to Crizotinib: The Importance of Choosing the Appropriate Next-Generation Sequencing Assay.

Identifying the druggable target is crucial for patients with nonsquamous advanced non-small cell lung cancer (NSCLC). This article adds to the spectrum of ROS1 fusion cases described in NSCLC. We describe a novel SLC12A2-ROS1 rearrangement that has not been previously reported in other cancers: a fusion that has clinical and radiological sensitivity to crizotinib. Fluorescence in situ hybridization detected the SLC12A2-ROS1 fusion and it was confirmed through hybrid capture-based next-generation sequencing (NGS); however, the fusion could not be detected by amplicon-based assay. The success of implementing NGS into routine clinical practice depends on the accuracy of testing. The test's methodological features should then be considered because they significantly affect the results. Given this patient's response to crizotinib, identifying patients with undescribed ROS1 fusions has important therapeutic implications. KEY POINTS: This is the first known description of an SLC12A2-ROS1 fusion. Considering the patient's clinical features and tumor response observed after crizotinib therapy, the authors confirm that this new rearrangement has relevant clinical impact for patients with non-small cell lung cancer. The success of implementing next-generation sequencing (NGS) into routine clinical practice depends on the accuracy of the testing. Different assays and NGS platforms can achieve differing results. Each assay's limitations need to be considered to ensure the quality of precision medicine in clinical practice.

[Subjective impact of COVID-19 pandemic among mental health service workers in Argentina]. / Impacto subjetivo de la pandemia de COVID-19 en los trabajadores de salud mental de la Argentina.

INTRODUCTION: The impact of the COVID-19 pandemic on health workers has been studied on an international level. However, mental health workers, who are also called upon to address such ailments both in the general population as well as in the health personnel, have not been asked about their experiences. METHODS: Seventy mental health workers in five regions of Argentina were interviewed between May and June 2020 regarding the subjective impact of changes in their work due to the pandemic. The responses were analyzed quantitatively and qualitatively. RESULTS: The results indicate emotions and experiences associated with a negative impact, in connection to feelings of tiresome, uncertainty, fear, anguish and anxiety and, to a lesser extent, some positive impacts are also described. More than a third of participants mentioned mixed feelings (i.e., being surprised, ambivalent, alert and sensitive). CONCLUSIONS: The personnel who are supposed to support the rest of the health workers are affected and experience having been relegated one more time to other aspects within the health care system. Focusing on learnings, having management roles, counting on colleagues, and agreeing with macro policies could be protective factors against the difficulties associated with the changes in work that the pandemic has imposed.

How Does the Amount and Composition of PM Deposited on Platanus acerifolia Leaves Change Across Different Cities in Europe?

Particulate matter (PM) deposited on Platanus acerifolia tree leaves has been sampled in the urban areas of 28 European cities, over 20 countries, with the aim of testing leaf deposited particles as indicator of atmospheric PM concentration and composition. Leaves have been collected close to streets characterized by heavy traffic and within urban parks. Leaf surface density, dimensions, and elemental composition of leaf deposited particles have been compared with leaf magnetic content, and discussed in connection with air quality data. The PM quantity and size were mainly dependent on the regional background concentration of particles, while the percentage of iron-based particles emerged as a clear marker of traffic-related pollution in most of the sites. This indicates that Platanus acerifolia is highly suitable to be used in atmospheric PM monitoring studies and that morphological and elemental characteristics of leaf deposited particles, joined with the leaf magnetic content, may successfully allow urban PM source apportionment.

Foliar nitrogen uptake in broadleaf evergreen Mediterranean forests: Fertilisation experiment with labelled nitrogen.

Atmospheric nitrogen (N) deposition in Mediterranean sclerophyllous forests of Holm oak (Quercus rotundifolia, Q. ilex) in Spain often exceeds empirical critical loads established for ecosystem conservation. There are still uncertainties on the capacity of canopy retention and uptake of the atmospheric N deposited of these forests. Studying and analysing all the forest nitrogen-cycle processes is essential to understand the potential effect of N deposition in these ecosystems. This study conducted a year-long short-term fertilisation experiment with labelled ammonium (15N-NH4) and nitrate (15N-NO3) to estimate foliar N absorption rates and assess the influence of leaf phenology and meteorological seasonal variations. Fertilising solutions were prepared to simulate low and high wet N deposition concentration, based on data reported from previous studies. Additionally, ecophysiological and meteorological measurements were collected to explore potential relationships between absorption rates, plant activity, and weather conditions. The results showed that Holm oak leaves were able to absorb both oxidised and reduced N compounds, with higher rates of NH4+ absorption. N recovery of both NH4+ and NO3- was higher in the low concentration treatments, suggesting reduced effectiveness of absorption as concentration increases. Foliar absorption rates were leaf-age dependent, with the highest values observed in young developing leaves. Foliar uptake showed seasonal changes with a clear reduction during the summer, linked to drought and dry weather conditions, and showing also smaller leaf net assimilation and stomatal conductance. During the rest of the year, foliar N absorption was not clearly associated to plant physiological activity but with environmental conditions. Our findings suggest that Holm oak canopies could absorb an important part of the incoming N deposition, but this process is compound, season and leaf phenology dependent. Further research is therefore needed to better understand and model this part of the N cycle.

Reduced precipitation can induce ecosystem regime shifts in lakes by increasing internal nutrient recycling.

Eutrophication is a main threat to continental aquatic ecosystems. Prevention and amelioration actions have been taken under the assumption of a stable climate, which needs reconsideration. Here, we show that reduced precipitation can bring a lake ecosystem to a more productive regime even with a decline in nutrient external load. By analyzing time series of several decades in the largest lake of the Iberian Peninsula, we found autocorrelated changes in the variance of state variables (i.e., chlorophyll and oxygen) indicative of a transient situation towards a new ecosystem regime. Indeed, exceptional planktonic diatom blooms have occurred during the last few years, and the sediment record shows a shift in phytoplankton composition and an increase in nutrient retention. Reduced precipitation almost doubled the water residence time in the lake, enhancing the relevance of internal processes. This study demonstrates that ecological quality targets for aquatic ecosystems must be tailored to the changing climatic conditions for appropriate stewardship.

Sodium-Glucose Cotransporter Type 2 Inhibitors Use in Elderly Polypathological Patients with Acute Heart Failure: PROFUND-IC Registry.

Background/Objectives: Heart failure (HF) is a highly prevalent clinical syndrome with serious morbidity and mortality. Furthermore, acute heart failure (AHF) is the main cause of hospital admission in people aged 65 years or more. Sodium-glucose cotransporter type 2 inhibitors (SGLT2is) have been shown to improve the survival and quality of life in patients with HF regardless of left ventricular ejection fraction (LVEF). Our aims were to describe the characteristics of adults with multiple pathologies admitted with acute heart failure as the main diagnosis and of the population treated with SGLT2is, as well as to evaluate if their use was associated with lower readmission and mortality rates. Methods: A prospective study of patients from the PROFUND-IC registry who were admitted with AHF as the main diagnosis was conducted. Clinical and analytical characteristics were analyzed, as well as readmissions and mortality. Descriptive and bivariate analyses of the sample between those taking SGLT2is and those who were not were performed, using the chi-square test for qualitative variables and Welch's test for quantitative measures, as well as the Fisher and Wilcoxon tests as indicated for nonparametric tests. Kaplan-Meier curves were constructed to analyze the readmission and mortality of patients at 12 months based on SGLT2i treatment. Finally, a propensity score matching was performed, guaranteeing that the observed effect of the drug was not influenced by the differences in the characteristics between the groups. Results: There were 750 patients included: 58% were women, and the mean age was 84 years. Functional class II according to the NYHA scale predominated (54%), and the mean LVEF was 51%. SGLT2 inhibitors were prescribed to only 28% of patients. Most of the patients were men (48.6% vs. 39.8%, p = 0.029), they were younger (82 vs. 84 years, p = 0.002), and their LVEF was lower (48% vs. 52%, p < 0.001). Lower mortality was observed in the group treated with SGLT2is, both during baseline admission (2.4% vs. 6.9%, p = 0.017) and at the 12-month follow-up (6.2% vs. 13%, p = 0.023); as well as a lower readmission rate (23.8% vs. 38.9%, p < 0.001). After the propensity score matching, a decrease in the 12-month readmission rate continued to be observed in the group treated with SGLT2is (p = 0.03). Conclusions: SGLT2is use was associated with lower readmission rates at the 12-month follow-up in older adults with multiple pathologies admitted with acute heart failure.

Evaluation of the clinical use of MGMT methylation in extracellular vesicle-based liquid biopsy as a tool for glioblastoma patient management.

Glioblastoma (GB) is a devastating tumor of the central nervous system characterized by a poor prognosis. One of the best-established predictive biomarker in IDH-wildtype GB is O6-methylguanine-DNA methyltransferase (MGMT) methylation (mMGMT), which is associated with improved treatment response and survival. However, current efforts to monitor GB patients through mMGMT detection have proven unsuccessful. Small extracellular vesicles (sEVs) hold potential as a key element that could revolutionize clinical practice by offering new possibilities for liquid biopsy. This study aimed to determine the utility of sEV-based liquid biopsy as a predictive biomarker and disease monitoring tool in patients with IDH-wildtype GB. Our findings show consistent results with tissue-based analysis, achieving a remarkable sensitivity of 85.7% for detecting mMGMT in liquid biopsy, the highest reported to date. Moreover, we suggested that liquid biopsy assessment of sEV-DNA could be a powerful tool for monitoring disease progression in IDH-wildtype GB patients. This study highlights the critical significance of overcoming molecular underdetection, which can lead to missed treatment opportunities and misdiagnoses, possibly resulting in ineffective therapies. The outcomes of our research significantly contribute to the field of sEV-DNA-based liquid biopsy, providing valuable insights into tumor tissue heterogeneity and establishing it as a promising tool for detecting GB biomarkers. These results have substantial implications for advancing predictive and therapeutic approaches in the context of GB and warrant further exploration and validation in clinical settings.

Phylogeography and postglacial expansion of the endangered semi-aquatic mammal Galemys pyrenaicus.

BACKGROUND: Species with strict ecological requirements may provide new insights into the forces that shaped the geographic variation of genetic diversity. The Pyrenean desman, Galemys pyrenaicus, is a small semi-aquatic mammal that inhabits clean streams of the northern half of the Iberian Peninsula and is endangered in most of its geographic range, but its genetic structure is currently unknown. While the stringent ecological demands derived from its aquatic habitat might have caused a partition of the genetic diversity among river basins, Pleistocene glaciations would have generated a genetic pattern related to glacial refugia. RESULTS: To study the relative importance of historical and ecological factors in the genetic structure of G. pyrenaicus, we used mitochondrial and intronic sequences of specimens covering most of the species range. We show, first, that the Pyrenean desman has very low levels of genetic diversity compared to other mammals. In addition, phylogenetic and dating analyses of the mitochondrial sequences reveal a strong phylogeographic structure of a Middle Pleistocene origin, suggesting that the main lineages arose during periods of glacial isolation. Furthermore, both the spatial distribution of nuclear and mitochondrial diversity and the results of species distribution modeling suggest the existence of a major glacial refugium in the northwestern part of the Iberian Peninsula. Finally, the main mitochondrial lineages show a striking parapatric distribution without any apparent exchange of mitochondrial haplotypes between the lineages that came into secondary contact (although with certain permeability to nuclear genes), indicating incomplete mixing after the post-glacial recolonization. On the other hand, when we analyzed the partition of the genetic diversity among river basins, the Pyrenean desman showed a lower than expected genetic differentiation among main rivers. CONCLUSIONS: The analysis of mitochondrial and intronic markers in G. pyrenaicus showed the predominant effects of Pleistocene glaciations on the genetic structure of this species, while the distribution of the genetic diversity was not greatly influenced by the main river systems. These results and, particularly, the discovery of a marked phylogeographic structure, may have important implications for the conservation of the Pyrenean desman.

Proteolysis, lipolysis, volatile compounds and sensory characteristics of Hispánico cheeses made using frozen curd from raw and pasteurized ewe milk.

Hispánico cheese, manufactured from a mixture of cow and ewe milk, is representative of cheese varieties made using milk from more than one animal species in Mediterranean countries. The shortage of ewe milk production in autumn hinders the uniformity of Hispánico cheese composition throughout the year. To surmount this inconvenience of ewe milk seasonality, curds made in spring from raw and pasteurized ewe milk were stored frozen and used four months later for the manufacture of Hispánico cheese. Experimental cheeses were made by mixing fresh curd from pasteurized cow milk with thawed curd from raw or pasteurized ewe milk, and control cheese from a mixture of pasteurized cow and ewe milk in the same proportion. Characteristics of experimental and control cheeses throughout a 60-d ripening period were investigated. On the one hand, the experimental cheese containing frozen curd from raw ewe milk showed the highest counts of staphylococci, Gram-negative bacteria and coliforms, the highest levels of aminopeptidase and esterase activity, and the highest concentrations of free amino acids, free fatty acids, alcohols and esters. On the other, the experimental cheese containing frozen curd from pasteurized ewe milk had concentrations of free amino acids, free fatty acids and volatile compounds similar to those of control cheese, with the only exception being a higher level of ketones. Flavour intensity reached the highest scores in the experimental cheese containing frozen curd from raw ewe milk, followed by the experimental cheese containing frozen curd from pasteurized ewe milk. Flavour quality scores of both experimental cheeses were similar, and lower than those of control cheese.

[Repercussions of COVID-19 on psychiatric inpatient care in Latin America and the Caribbean]. / Repercusiones de la COVID-19 en la Internación Psiquiátrica en América Latina y el Caribe.

Objetive: To characterise the impact of the COVID-19 pandemic on psychiatric hospitalisations in the Latin American and Caribbean (LAC) region. Methods: Descriptive study. 85 semi-structured interviews were conducted with health workers involved with psychiatric hospitalisations in general hospitals (GHs) and specialised psychiatric hospitals (SHs) from 18 LAC countries. The interviews were done between 8 May and 30 June 2020. The data were analysed quantitatively and qualitatively. Results: An initial decrease in the demand for hospitalisation is reported, attributed to the population's fear of approaching health services as well as restrictions on mobility. Stricter criteria for hospitalisation were reported with a double focus on the acute within the acute. The length of hospitalisations were mixed, with both increases and decreases in GHs and SHs. The therapeutic offer was drastically reduced, and interaction between hospitalised people and their support networks was restricted. Conclusions: In the COVID-19 context, hospitalisation seems to be not the last but the only alternative for psychiatric treatment. The decrease in the number of beds in SHs could be a positive aspect for the reform of psychiatric care, but it is questioned since this reduction also occurs in GHs.

Ozone and Temperature May Hinder Adaptive Capacity of Mediterranean Perennial Grasses to Future Global Change Scenarios.

Climate warming is recognized as a factor that threatens plant species in Mediterranean mountains. Tropospheric ozone (O3) should also be considered as another relevant stress factor for these ecosystems since current levels chronically exceed thresholds for plant protection in these areas. The main aim of the present study was to study the sensitivity of four Mediterranean perennial grasses to O3 and temperature based on plant growth, gas exchange parameters (photosynthesis-A, stomatal conductance-gs, and water use efficiency-WUE), and foliar macro- (N, K, Ca, Mg, P, and S) and micronutrients (B, Cu, Fe, Mn, Mo, and Zn) content. The selected species were grasses inhabiting different Mediterranean habitats from mountain-top to semi-arid grasslands. Plants were exposed to four O3 treatments in Open-Top chambers, ranging from preindustrial to above ambient levels, representing predicted future levels. Chamber-less plots were considered to study the effect of temperature increase. Despite the general tolerance of the grasses to O3 and temperature in terms of biomass growth, WUE and foliar nutrient composition were the most affected parameters. The grass species studied showed some degree of similarity in their response to temperature, more related with phylogeny than to their tolerance to drought. In some species, O3 or temperature stress resulted in low A or WUE, which can potentially hinder plant tolerance to climate change. The relationship between O3 and temperature effects on foliar nutrient composition and plant responses in terms of vegetative growth, A, gs, and WUE constitute a complex web of interactions that merits further study. In conclusion, both O3 and temperature might be modifying the adaptation capacity of Mediterranean perennial grass species to the global change. Air pollution should be considered among the driving favors of biodiversity changes in Mediterranean grassland habitats.

Repercussions of COVID-19 on psychiatric inpatient care in Latin America and the Caribbean.

OBJETIVE: To characterise the impact of the COVID-19 pandemic on psychiatric hospitalisations in the Latin American and Caribbean (LAC) region. METHODS: Descriptive study. 85 semi-structured interviews were conducted with health workers involved with psychiatric hospitalisations in general hospitals (GHs) and specialised psychiatric hospitals (SHs) from 18 LAC countries. The interviews were done between 8 May and 30 June 2020. The data were analysed quantitatively and qualitatively. RESULTS: An initial decrease in the demand for hospitalisation is reported, attributed to the population's fear of approaching health services as well as restrictions on mobility. Stricter criteria for hospitalisation were reported with a double focus on the acute within the acute. The length of hospitalisations were mixed, with both increases and decreases in GHs and SHs. The therapeutic offer was drastically reduced, and interaction between hospitalised people and their support networks was restricted. CONCLUSIONS: In the COVID-19 context, hospitalisation seems to be not the last but the only alternative for psychiatric treatment. The decrease in the number of beds in SHs could be a positive aspect for the reform of psychiatric care, but it is questioned since this reduction also occurs in GHs.

A nationwide monitoring of atmospheric microplastic deposition.

Plastic production continues to increase every year, yet it is widely acknowledged that a significant portion of this material ends up in ecosystems as microplastics (MPs). Among all the environmental compartments affected by MPs, the atmosphere remains the least well-known. Here, we conducted a one-year simultaneous monitoring of atmospheric MPs deposition in ten urban areas, each with different population sizes, economic activities, and climates. The objective was to assess the role of the atmosphere in the fate of MPs by conducting a nationwide quantification of atmospheric MP deposition. To achieve this, we deployed collectors in ten different urban areas across continental Spain and the Canary Islands. We implemented a systematic sampling methodology with rigorous quality control/quality assurance, along with particle-oriented identification and quantification of anthropogenic particle deposition, which included MPs and industrially processed natural fibres. Among the sampled MPs, polyester fibres were the most abundant, followed by acrylic polymers, polypropylene, and alkyd resins. Their equivalent sizes ranged from 22 µm to 398 µm, with a median value of 71 µm. The particle size distribution of MPs showed fewer large particles than expected from a three-dimensional fractal fragmentation pattern, which was attributed to the higher mobility of small particles, especially fibres. The atmospheric deposition rate of MPs ranged from 5.6 to 78.6 MPs m-2 day-1, with the higher values observed in densely populated areas such as Barcelona and Madrid. Additionally, we detected natural polymers, mostly cellulosic fibres with evidence of industrial processing, with a deposition rate ranging from 6.4 to 58.6 particles m-2 day-1. There was a positive correlation was found between the population of the study area and the median of atmospheric MP deposition, supporting the hypothesis that urban areas act as sources of atmospheric MPs. Our study presents a systematic methodology for monitoring atmospheric MP deposition.

Identifying biomarkers of treatment response to ciclosporin in atopic dermatitis through multiomic predictive modelling: DERMATOMICS study protocol.

INTRODUCTION: There is a need to optimise the management of atopic dermatitis (AD), improving the efficacy of treatments and reducing the toxicity associated with them. Although the efficacy of ciclosporine (CsA) in the treatment of AD has been thoroughly documented in the literature, the optimal dose has not been yet established. The use of multiomic predictive models of treatment response could optimise CsA therapy in AD. METHODS AND ANALYSIS: The study is a low-intervention phase 4 trial to optimise the treatment of patients with moderate-severe AD requiring systemic treatment. The primary objectives are to identify biomarkers that could allow for the selection of responders and non-responders to first-line treatment with CsA and to develop a response prediction model to optimise the CsA dose and treatment regimen in responding patients based on these biomarkers. The study is divided into two cohorts: the first comprised of patients starting treatment with CsA (cohort 1), and the second, of patients already receiving or who have received CsA therapy (cohort 2). ETHICS AND DISSEMINATION: The study activities began following authorisation by the Spanish Regulatory Agency (AEMPS) and the Clinical Research Ethics Committee of La Paz University Hospital approval. Trial results will be submitted for publication in an open access peer-reviewed medical speciality-specific publication.Trial registration of this study can be located at the EU Clinical Trials Register, available from https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en. Our clinical trial was registered in the website before the enrolment of the first patient complying with European regulations. EU Clinical Trials Register is a primary registry according the WHO. Once our trial was included in a primary and official registry, in order to extend the accessibility to our research, we also registered it retrospectively in clinicaltrials.gov; however, this is not mandatory as per our regulation. TRIAL REGISTRATION NUMBER: NCT05692843.