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Clopidogrel is widely used worldwide as an antiplatelet therapy in patients with acute coronary disease. Genetic factors influence interindividual variability in response. Some studies have explored the polygenic contributions in the drug response, generating pharmacogenomic risk scores (PgxPRS). Importantly, these factors are less explored in underrepresented populations, such as Latin-American countries. Identifying patients at risk of high-on-treatment platelet reactivity (HTPR) is highly valuable in translational medicine. In this study we used a custom next-generation sequencing (NGS) panel composed of 91 single nucleotide polymorphisms (SNPs) and 28 genes related to clopidogrel metabolism, to analyze 70 patients with platelet reactivity values, assessed through closure time (CT). Our results demonstrated the association of SNPs with HTPR and non-HTPR, revealing the strongest associations with rs2286823 (OR: 5,0; 95% CI: 1,02-24,48; p: 0,03), rs2032582 (OR: 4,41; 95% CI: 1,20-16,12; p: 0,019), and rs1045642 (OR: 3,38; 95% CI: 0,96-11,9; p: 0,05). Bivariate regression analysis demonstrated the significant association of several SNPs with the CT value, a "surrogate" biomarker of clopidogrel response. Exploratory results from the LASSO regression model showed a high discriminatory capacity between HTPR and non-HTPR patients (AUC: 0,955), and the generated PgxPRS demonstrated a significant negative association between the risk score, CT value, and the condition of HTPR and non-HTPR. To our knowledge, our study addresses for the first time the analysis of the polygenic contribution in platelet reactivity using NGS and establishes PgxPRS derived from the LASSO model. Our results demonstrate the polygenic implication of clopidogrel response and offer insights applicable to the translational medicine of antiplatelet therapy in an understudied population., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Echeverría et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The current definition of severe malaria in non-endemic areas follows WHO criteria, which mainly target children in malaria-endemic areas, potentially misclassifying cases in non-endemic regions. We assessed the performance of a modified severe malaria classification criteria within our patient cohort., Methods: A cohort study of patients managed for malaria in a non-endemic setting (2005-2023) was analyzed. We classified patients into severe malaria (SM) using WHO 2013 criteria except for hyperparasitemia, where 2 % threshold was applied. Patients with SM were distinguished as very severe malaria (VSM) when presenting at least one of the following conditions: parasitemia >10 %, pulmonary edema, impaired consciousness, seizures, renal failure, metabolic acidosis or hyperlactatemia, shock or hypoglycemia. In patients with SM and no criteria for VSM, less severe malaria (LSM) was defined by: 2-10 % parasitemia, hyperbilirubinemia, prostration, anemia or minor bleeding. The primary composite outcome was death or the need for a life-saving intervention, as analyzed in the three comparative groups. Secondary outcome was the prevalence of co-infections., Results: Among 506 patients with malaria, 176 (34.8 %) presented with SM. A total of 37 (7.3 %) patients developed a life-threatening condition, namely death (n = 4) and/or the need for life-saving interventions (n = 34). All fatalities and 33 out of the 34 life-saving interventions occurred in the VSM group. Patients in LSM group did not develop any life-threatening conditions. As to co-infections, 28 (5.5 %) patients had a community-acquired co-infection, with no differences between groups (p = 0.763)., Conclusions: Severity criteria definitions would benefit from a review when assessing patients with malaria in non-endemic areas. Within the spectrum of SM, patients reclassified as LSM have a low risk of developing a life-threatening condition and present low co-infection incidence and could benefit from management out of intensive care units and a restrictive use of empirical antibiotics., 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 Ltd.. All rights reserved.)

Background: n Growth of international travel to malarial areas over the last decades has contributed to more travelers taking malaria prophylaxis. Travel-related symptoms may be wrongly attributed to malaria prophylaxis and hinder compliance. Here, we aimed to assess the frequency of real-time reporting of symptoms by travelers following malaria prophylaxis using a smartphone app. Method: Adult international travelers included in this single-center study (Barcelona, Spain) used the smartphone Trip Doctor ® app developed by our group for real-time tracking of symptoms and adherence to prophylaxis. Results: Six hundred four ( n  = 604) international travelers were included in the study; 74.3% (449) used the app daily, and for one-quarter of travelers, malaria prophylaxis was prescribed. Participants from the prophylaxis group traveled more to Africa (86.7% vs. 4.3%; p < 0.01) and to high travel medical risk countries (60.8% vs. 18%; p < 0.01) and reported more immunosuppression (30.8% vs. 23.1% p < 0.01). Regarding symptoms, no significant intergroup differences were observed, and no relationship was found between the total number of malarial pills taken and reported symptoms. Conclusions: In our cohort, the number of symptoms due to malaria prophylaxis was not significantly higher than in participants for whom prophylaxis was not prescribed, and the overall proportion of symptoms is higher compared with other studies.

Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare.

Environmental crimes are a global issue due to the damage they cause to landscapes and ecosystems. This study focused on characterizing environmental crimes in the Canary Islands (Spain). Four categories of environmental crimes related to construction, mining and tilling, solid waste, and liquid waste) were defined and analysed. A total of 28 databases were generated, corresponding to each of the 7 major islands and each environmental crime typology. Each database was linked to information on land use and the socioeconomic and physical characteristics of the territory. For each database, firstly a descriptive statistical analysis was conducted, followed by the generation of a regularized Random Forest model with the aim of identifying characteristics that may be related to the location of environmental crimes. The results showed that, in most cases, proximity to residential accommodations, agricultural areas and industrial zones act as the main explanatory features of the distribution of environmental crimes. Furthermore, a marked pattern of concentration of environmental crimes in the coastal belt of the islands was observed, mainly associated with urban-tourist development since the 1960s and 1970s., Competing Interests: Declaration of competing interest I would like to submit the manuscript entitled “Mapping environmental crime to characterize human impacts on islands: an applied and methodological research in Canary Islands” by Quesada-Ruiz. L.C., Garcia-Romero, L. and Ferrer-Valero, N. to be considered for publication as an original review article in Journal of Environmental Management. We declare that this manuscript is original, has not been published before and is not currently being considered for publication elsewhere. We know of no conflicts of interest associated with this publication, and there has been no significant financial support for this work that could have influenced its outcome. As corresponding Quesada-Ruiz, L. I confirm that the manuscript has been read and approved for submission by all the named authors., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The escalating global anthropogenic activities associated with industrial development have led to the increased introduction of heavy metals (HMs) into marine environments through effluents. This study aimed to assess the toxicity of three HMs (Cr, Cu, and Cd) on organisms spanning different trophic levels: Phaeodactylum tricornutum (a primary producer), Artemia salina (a primary consumer), and Aurelia aurita (a secondary consumer). The EC 50 values obtained revealed varying relative toxicities for the tested organisms. Phaeodactylum tricornutum exhibited the highest sensitivity to Cu, followed by Cd and Cr, while Artemia salina displayed the highest sensitivity to Cr, followed by Cu and Cd. A. aurita , on the other hand, demonstrated the highest sensitivity to Cu, followed by Cr and Cd. This experimental investigation further supported previous studies that have suggested A. aurita as a suitable model organism for ecotoxicity testing. Our experiments encompassed sublethal endpoints, such as pulsation frequency, acute effects, and mortality, highlighting different levels of sensitivity among the organisms.

Background: Trypanosoma cruzi causes Chagas disease (CD), a potentially fatal disease characterized by cardiac disorders and digestive, neurological or mixed alterations. T. cruzi is transmitted to humans by the bite of triatomine vectors; both the parasite and disease are endemic in Latin America and the United States. In the last decades, population migration has changed the classic epidemiology of T. cruzi, contributing to its global spread to traditionally non-endemic countries. Screening is recommended for Latin American populations residing in non-endemic countries., Methods: The present study analyzes the epidemiological characteristics of 2,820 Latin American individuals who attended the International Health Service (IHS) of the Hospital Clinic de Barcelona between 2002 and 2019. The initial assessment of organ damage among positive cases of T. cruzi infection was analyzed, including the results of electrocardiogram (ECG), echocardiogram, barium enema and esophagogram., Results: Among all the screened individuals attending the clinic, 2,441 (86.6%) were born in Bolivia and 1,993 (70.7%) were female. Of individuals, 1,517 (81.5%) reported previous exposure to the vector, which is a strong risk factor associated with T. cruzi infection; 1,382 individuals were positive for T. cruzi infection. The first evaluation of individuals with confirmed T. cruzi infection, showed 148 (17.1%) individuals with Chagasic cardiomyopathy, the main diagnostic method being an ECG and the right bundle branch block (RBBB) for the most frequent disorder; 16 (10.8%) individuals had a normal ECG and were diagnosed of Chagasic cardiomyopathy by echocardiogram., Conclusions: We still observe many Latin American individuals who were at risk of T. cruzi infection in highly endemic areas in their countries of origin, and who have not been previously tested for T. cruzi infection. In fact, even in Spain, a country with one of the highest proportion of diagnosis of Latin American populations, T. cruzi infection remains underdiagnosed. The screening of Latin American populations presenting with a similar profile as reported here should be promoted. ECG is considered necessary to assess Chagasic cardiomyopathy in positive individuals, but echocardiograms should also be considered as a diagnostic approach given that it can detect cardiac abnormalities when the ECG is normal., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Laynez-Roldán et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Identifying the causes of Acute Undifferentiated Febrile Illness (AUFI) is key to improve the management of returning travellers with fever. We evaluated a BioFire®FilmArray® prototype panel of multiplex nucleic acid amplification tests (NAAT) targeting different relevant pathogens in travellers returning with fever., Methods: Prospective, multicentre study to evaluate a prototype panel in whole blood samples of adult international travellers presenting with AUFI in three European travel Clinics/Hospitals (November 2017-November 2019). We evaluated 15 target analytes: Plasmodium spp., Plasmodium falciparum, Plasmodium knowlesi, Plasmodium malariae, Plasmodium ovale, Plasmodium vivax, chikungunya virus, dengue virus, Zika virus, Anaplasma phagocytophilum, Borrelia spp., Leptospira spp., Orientia tsutsugamushi, Rickettsia spp. and Salmonella spp. Results were compared with composite reference standards (CRSs) for each target infection, including direct methods [smear microscopy, rapid diagnostic test (RDT), reference NAAT and blood cultures] and indirect methods (paired serology)., Findings: Among 455 travellers with AUFI, 229 target infections were diagnosed; the prototype panel detected 143 (overall sensitivity and specificity of 62.5 and 99.8%, respectively). The panel identified all Plasmodium infections (n = 82). Sensitivity for dengue (n = 71) was 92.9, 80.8 and 68.5% compared with RDT, NAAT and CRS, respectively. Compared with direct methods and CRS, respectively, the prototype panel detected 4/4 and 4/6 chikungunya, 2/2 and 4/29 Leptospira spp., 1/1 and 1/6 O. tsutsugamushi and 2/2 and 2/55 Rickettsia spp., but 0/2 and 0/10 Zika, 0/1 and 0/11 A. phagocytophylum and 0/3 Borrelia spp. diagnosed by serology and only 1/7 Salmonella spp. diagnosed by blood cultures. 77/86 (89.5%) infections not detected by the panel were diagnosed by serology., Interpretation: The prototype panel allowed rapid and reliable diagnosis for malaria, dengue and chikungunya. Further improvements are needed to improve its sensitivity for Zika and important travel-related bacterial infections., (© International Society of Travel Medicine 2023. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: COVID-19 disease is a serious global health problem. Few treatments have been shown to reduce mortality and accelerate time to recovery. The aim of this study was to evaluate the potential effect of a food supplement (probiotics, prebiotics, vitamin D, zinc and selenium) in patients admitted with COVID-19., Methods: A prospective randomized non-blinded clinical trial was conducted in a sample of 162 hospitalized patients diagnosed with COVID-19 recruited over eight months. All patients received standard treatment, but the intervention group ( n = 67) was given one food supplement stick daily during their admission. After collecting the study variables, a statistical analysis was performed comparing the intervention and control groups and a multivariate analysis controlling for variables that could act as confounding factors., Results: ROC curve analysis with an area under the curve (AUC) value of 0.840 ( p < 0.001; 95%CI: 0.741-0.939) of the food supplement administration vs. recovery indicated good predictive ability. Moreover, the intervention group had a shorter duration of digestive symptoms compared with the control group: 2.6 ± 1.3 vs. 4.3 ± 2.2 days ( p = 0.001); patients with non-severe disease on chest X-ray had shorter hospital stays: 8.1 ± 3.9 vs. 11.6 ± 7.4 days ( p = 0.007)., Conclusions: In this trial, the administration of a food supplement (Gasteel Plus ® ) was shown to be a protective factor in the group of patients with severe COVID-19 and allowed early recovery from digestive symptoms and a shorter hospital stay in patients with a normal-mild-moderate chest X-ray at admission (ClinicalTrials.gov number, NCT04666116).

Squamous cell carcinoma (SCC) is the most common malignant neoplasm of the oral cavity. The performance of END (elective neck dissection) in cases of maxillary SCC is controversial because the literature traditionally classified maxillary tumors as having low metastatic potential. The aim of this systematic review and meta-analysis was to determine the percentage of occult cervical metastases in maxillary SCC to identify in which cases there is the need to perform an END. We searched the PubMed database to select articles dated from 2000 to 2020 that fulfilled our inclusion criteria; finally, we reviewed 27 manuscripts. We show that the overall cervical and occult metastases rate was 35% and 19%, respectively. For T1, the percentage of occult metastasis rate was 11%; for T2, it was 16%; for T3, it was 20%; and for T4, it was 32%. We suggest END (levels I-II-III) as treatment to T3/T4 cN0 patients., (© 2022 Wiley Periodicals LLC.)

Background: Diagnosis of undifferentiated non-malaria fevers (NMF) in returning travellers is a great challenge. Currently, there is no consensus about the use of empirical antibiotics in returning travellers with undifferentiated NMF. Although studies in endemic areas showed that a wide range of pathogens implicated in undifferentiated NMF are treatable with doxycycline, the role of doxycycline in returning travellers with fever still has to be explored., Methods: Prospective European multicentre cohort study of febrile international travellers (November 2017-November 2019). Immunological and molecular diagnostic techniques for doxycycline responding illnesses (DRI) agents such as Anaplasma phagocytophilum, spotted fever group Rickettsia spp., typhus group Rickettsia spp., Coxiella burnetii, Bartonella spp., Orientia tsutsugamushi, Borrelia miyamotoi, Borrelia recurrentis and Leptospira spp. were systematically performed in all patients with undifferentiated NMF. We estimated the prevalence and predictive factors of DRI in returning travellers with undifferentiated NMF., Results: Among 347 travellers with undifferentiated NMF, 106 (30·5%) were finally diagnosed with DRI. Only 57 (53·8%) of the 106 DRI infections were diagnosed by the standard of care. The main causes of DRI were: 55 (51·9%) Rickettsia spp., 16 (15·1%) C. burnetii; 15 (14·2%) Bartonella spp.; 13 (12·3%) Leptospira spp. and 10 (9·5%) A. phagocytophilum. The only predictive factor associated with DRI was presenting an eschar (aOR 39·52, 95%CI 4·85-322·18). Features of dengue such as retro-orbital pain (aOR 0·40, 95%CI 0·21-0·76) and neutropenia (aOR 0·41, 95%CI 0·21-0·79) were negatively associated with DRI., Conclusions: Although DRI are responsible for 30% of undifferentiated NMF cases in travellers, those are seldom recognized during the first clinical encounter. Empirical treatment with doxycycline should be considered in returning travellers with undifferentiated fever and negative tests for malaria and dengue, particularly when presenting severe illness, predictive factors for rickettsiosis or no features of dengue., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society of Travel Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The new WHO air quality guidelines indicate that the air pollution disease burden is greater than previously reported. We aimed to estimate the air pollution disease burden and its economic cost in Barcelona to inform local action., Methods: We used a quantitative health impact assessment to estimate the non-accidental mortality and incidence of childhood asthma and lung cancer attributable to long-term air pollution exposure in the city of Barcelona (Spain) in 2018-2019. We used the population weighted mean of PM 2.5 and NO 2 assigned at the geocoded address during the study period and the 2021 WHO air quality guidelines as counterfactual scenario to estimate new annual cases attributable to each pollutant separately and combined. We estimated the social cost of attributable deaths and the health care cost of childhood asthma and lung cancer attributable cases. We also estimated attributable mortality by city district and the mortality avoidable by achieving the WHO air quality interim targets., Results: Mean exposure was 17 μg/m 3 for PM 2.5 and 39 μg/m 3 for NO 2 . Total combined air pollution attributable mortality was 13% (95%CI = 9%-17%), corresponding to 1,886 deaths (95%CI = 1,296-2,571) and a social cost of €1,292 million (95%CI = 888-1,762) annually. Fifty-one percent (95%CI = 21%-71%) and 17% (95%CI = 7%-29%) of new cases of childhood asthma and lung cancer were attributable to air pollution with a health care cost of €4.3 and €2.7 million, respectively. Achieving the first unmet WHO air quality interim targets for PM 2.5 and for NO 2 would avoid 410 deaths and €281 million annually., Conclusion: Air pollution in Barcelona represents a huge disease and economic burden, which is greater than previous estimates. Much stronger measures to reduce PM 2.5 and NO 2 levels are urgently needed. Until the WHO air quality guidelines are met in the city, achieving each WHO air quality interim targets would avoid hundreds of deaths each year., 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 Elsevier Inc. All rights reserved.)

Dengue fever is a serious and growing public health problem in Latin America and elsewhere, intensified by climate change and human mobility. This paper reviews the approaches to the epidemiological prediction of dengue fever using the One Health perspective, including an analysis of how Machine Learning techniques have been applied to it and focuses on the risk factors for dengue in Latin America to put the broader environmental considerations into a detailed understanding of the small-scale processes as they affect disease incidence. Determining that many factors can act as predictors for dengue outbreaks, a large-scale comparison of different predictors over larger geographic areas than those currently studied is lacking to determine which predictors are the most effective. In addition, it provides insight into techniques of Machine Learning used for future predictive models, as well as general workflow for Machine Learning projects of dengue fever.

Purpose: The aim of the present investigation is to study the relationship of ventricular global longitudinal strain (GLS) and ultrasound lung comets (ULC) formation to establish a link between extravascular pulmonary water formation and cardiac contractile dysfunction., Methods: This is a prospective observational study including 14 active military divers. The subjects performed two sea dives of 120 min each with a semi-closed SCUBA circuit at 10 m depth. Divers were examined at baseline, 15 min (D1) and 60 min (D2) after diving. The evaluation included pulmonary and cardiac echography (including speckle tracking techniques). Blood samples were drawn at baseline and after diving, assessing hs-TnT and Endothelin-1., Results: ULC were detected in 9 (64.2%) and 8 (57.1%) of the subjects after D1 and D2 respectively. No differences were found in right and left ventricular GLS after both immersions (RV: Baseline:  - 17.9 4.9 vs. D1:  - 17.2 6.5 and D2:  - 16.7 5.8 s -1 ; p = 0.757 and p = 0.529; LV: Baseline:  - 17.0 2.3 vs. D1:  - 17.4 2.1 and D2:  - 16.9 2.2 s -1 ; p = 0.546 and p = 0.783). However, a decrease in atrial longitudinal strain parameters have been detected after diving (RA: Baseline: 35.5 9.2 vs. D1: 30.3 12.8 and D2: 30.7 13.0 s -1 ; p = 0.088 and p = 0.063; LA: Baseline: 39.0 10.0 vs. D1: 31.6 6.1 and D2: 32.4 10.6 s -1 ; p = 0.019 and p = 0.054)., Conclusion: In the present study, no ventricular contractile dysfunction was observed. However, increase pulmonary vasoconstriction markers were present after diving., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sporadic Legionnaires' disease is frequently detected in commercial truck drivers. We report 2 sporadic cases of this disease in Barcelona, Spain, that occurred during December 2019 and September 2020. Laboratory findings were consistent with windshield wiper fluid without added screen wash as a possible source of infection for both cases.

Foredunes in arid coastal dune systems comprise nebkhas, which originate by interactions between vegetation and aeolian sedimentation. While continuous foredunes in temperate climates have been widely studied, knowledge of interactions between biotic and abiotic drivers in foredunes formed by nebkha is still scarce. With the aim of exploring variables affecting arid foredunes, a range of morphological, sedimentological, and vegetation characteristics were measured on a single nebkha formed by a Traganum moquinii plant located in the foredune of Caleta de Famara beach (Lanzarote, Canary Islands). Variables were sampled at 120 plots in a 0.5 × 0.5 m square grid. A two-step process using multiple linear regression (MLR) analyses was developed to characterize 1) the influence that morphological variables and distance from the sea have on plant and sediment patterns on nebkha, and 2) the influence of plants on depositional sediment characteristics. Results indicate close relationships between distance from the sea, plant coverage, and sediment patterns. Empirical results were used to develop a conceptual model that explains the spatial distribution of bio- and geo-morphological characteristics of an arid nebkha foredune., Competing Interests: Declaration of competing interest No conflict of interest exists., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)