Determination of regulated perfluoroalkyl substances (PFAS) in drinking water according to Directive 2020/2184/EU.

Perfluoroalkyl substances (PFAS) are chemical compounds that have been widely used in industry and manufacture. Occurrence, together with persistence and recent toxicological effects data, has promoted the regulation of 20 PFAS (carboxylic and sulfonic) acids in drinking water through the recent Directive 2020/2184/EU. This Regulation included PFAS with different carbon chain lengths (from C4 to C13) and limited the total PFAS concentration (as sum) to a maximum of 0.1 µg/L, for which law-enforcement analytical methods are required. In this work, three different methodologies have been developed and evaluated as regards their performance to determine those 20 PFAS in tap and bottled water, based on on-line and off-line solid-phase extraction (SPE) and direct injection. In all cases, ultra-high pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was used as a determination technique. Off-line SPE with Oasis Weak Anion Exchange (WAX) cartridges provided the best results in terms of limits of quantification (LOQ ≤ 0.3 ng/L) and accuracy (R ≥ 70%) in drinking water samples. On-line SPE and direct injection presented some drawbacks such as background contamination problems and lower accuracies for the least polar compounds. This off-line SPE methodology was then applied to the analysis of 46 drinking water samples (11 commercial bottled samples, 23 Spanish and 12 international tap water samples). Ten PFAS were quantified in such samples at concentrations and detection frequencies ranging from 0.1 to 20.1 ng/L and 2 to 91%, respectively. However, the sum concentration did not surpass the established limit in any sample.

Wastewater-based epidemiology to assess pharmaceutical consumption. Spanish perspective.

Wastewater-based epidemiology (WBE) is a well-established approach that can provide objective and real-time data on the consumption of substances such as pharmaceuticals. However, most of the studies reported so far compares consumption data obtained using WBE with those derived from prescription data from public health systems, which is often incomplete and might represent a source of uncertainty. This study aims to compare the measured pharmaceutical consumption back calculated with the WBE approach with consumption derived from dispensed pharmaceuticals in two regions of Spain, managed by two different Health Systems. To do so, a group of 17 pharmaceuticals, including the most representative ones of every therapeutic family, were monitored in influent wastewater (IWW) samples collected over a week campaign in spring 2022 at four different wastewater treatment plants (WWTPs) in Spain: two WWTPs in Madrid city (center of Spain) and two WWTPs in Catalonia (Northeast of Spain). Population-normalized daily loads (PNDL) revealed that the patterns of pharmaceutical occurrence in the different WWTPs are very similar, being acetaminophen, 4-acetamidoantipyrine and valsartan the pharmaceuticals with the highest PNDL values: 17162 ± 1457 mg day-1 1000 inh-1 for acetaminophen, 2365 ± 696 and 2429 ± 263 mg day-1 1000 inh-1 for 4-acetamidoantipyrine, 2006 ± 541 and 2041 ± 352 mg day-1 1000 inh-1 for valsartan. Pharmaceutical PNLDs were then transformed into measured pharmaceutical consumption (MC) and compared with dispensed consumption (DC) data obtained from the pharmacies in the catchment area where the WWTPs are located. A ratio MC/DC within 0.8 to 1.2 was obtained for 11 out of the 17 studied pharmaceuticals. Highlighting a match in all the cardiovascular system pharmaceuticals, with the exception of losartan (1.29-1.39 ratio) and valsartan (1.35-1.43) in all WWTPs. In summary, the degree of correlation between MC/DC is higher than those previously reported comparing with the prescribed pharmaceutical consumption.

Vaccination strategies for patients under monoclonal antibody and other biological treatments: an updated comprehensive review based on EMA authorizations to January 2024.

INTRODUCTION: Monoclonal antibodies (mAbs) and other biological agents are being increasingly approved in the last years with very different indications. Their highly heterogeneous immunosuppressive effects, mechanisms of action and pharmacokinetics require comprehensive individualized vaccination schedules. AREAS COVERED: Vaccination for immunocompromised patients. Prevention and treatment with mAbs and other biological therapies. EXPERT OPINION: Current recommendations on vaccine schedules for patients under mAbs or other biological treatments are based on expert opinions and are not individualized according to each vaccine and treatment. No studies are focusing on the high heterogeneity of these agents, that are exponentially developed and used for many different indications. Recent paradigm changes in vaccine development (boosted by the COVID-19 pandemic) and in the mAbs use for prophylactic purposes (changing 'vaccination' by 'immunization' schedules) has been witnessed in the last years. We aimed at collecting all mAbs used for treatment or prevention, approved as of 1 January 2024, by the EMA. Based on available data on mAbs and vaccines, we propose a comprehensive guide for personalizing vaccination. Recent vaccine developments and current population strategies (e.g. zoster vaccination or prophylactic nirsevimab) are discussed. This review aims to be a practical guideline for professionals working in vaccine consultations for immunosuppressed patients.

Bioaccessibility of plastic-related compounds from polymeric particles in marine settings: Are microplastics the principal vector of phthalate ester congeners and bisphenol A towards marine vertebrates?

Marine vertebrates are known to ingest significant amounts of microplastics (MPs). Once ingested, MPs might cause gastrointestinal injuries and serve as a path of harmful plastic components, such as phthalate esters (PAEs) and bisphenol A (BPA) in the food chain. However, there is a lack of standardized in-vitro methods capable of simulating fish uptake of chemicals from MPs in the environment as potential vectors of such contaminants. In this work, leaching and in-vitro oral bioaccessibility testing of PAEs and BPA from MPs were conducted batchwise using artificial seawater and gut fluids mimicking gastric, intestinal, and gastrointestinal compartments of marine vertebrates at physiological temperature. The environmental and physiologically relevant extraction tests were applied to medium-density polyethylene (PE) and polyvinyl chloride (PVC) certified reference materials containing eight PAEs of varying hydrophobicity, namely, dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate, benzylbutyl phthalate, diethylhexyl phthalate, di-n-octyl phthalate, diisononyl phthalate and diisodecyl phthalate, and BPA (only in PE) as MP surrogates with realistic analyte concentrations for primary MPs. The analysis of the leachates/gut fluid extracts was performed via dilute-and-shoot by ultra-high performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Only the most hydrophilic compounds, i.e. DMP, DEP and BPA, were found to get released significantly in saline waters, and exhibited the highest oral bioaccessibility rates (34-83 %). Based on our results, a dual-compartment physiologically relevant gastrointestinal test is recommended for appropriate estimation of fish bioaccessibility. The fish daily intakes of DMP, DEP and BPA from MPs, and seawater ingestion as well were estimated using several contamination scenarios (10th percentile as low level, 50th percentile as medium level and 90th percentile as high level contamination) based on probabilistic distributions and cumulative probability curves of measured environmental concentrations of (i) MP in seawater throughout the world, (ii) DMP, DEP and BPA in beached MP and those sampled in the open ocean (including both incurred and adsorbed contaminants), and (iii) DMP, DEP and BPA in seawater as reported in recent literature. Under a medium-level concentration scenario (50th percentile) in marine settings, and taking the gastrointestinal bioaccessibility factor into account, the daily intake of DMP, DEP and BPA from MPs accounted for a mere 0.02 % of the waterborne contribution. Hence, the ingestion of MPs should not be considered the primary route of fish exposure to BPA and the most polar PAEs in marine environments. However, more studies on the local and global scales using the continuously available data in the literature for mass concentrations of MP and additives in marine settings are needed for further confirmation of our findings.

[4]Rhombene: Solution-Phase Synthesis and Application in Distributed Feedback Lasers With Emission Beyond 830†nm.

Graphene-like molecules with multiple zigzag edges are emerging as promising gain materials for organic lasers. Their emission wavelengths can vary widely, ranging from visible to near-infrared (NIR), as the molecular size increases. Specifically, rhombus-shaped molecular graphenes with two pairs of parallel zigzag edges, known as [n]rhombenes, are excellent candidates for NIR lasers due to their small energy gaps. However, synthesizing large-size rhombenes with emission beyond 800 nm in solution remains a significant challenge. In this study, we present a straightforward synthesis of an aryl-substituted [4]rhombene derivative, [4]RB-Ar, using a method that combines intramolecular radical-radical coupling with Bi(OTf)3-mediated cyclization of vinyl ethers. The structure of [4]RB-Ar was confirmed through X-ray crystallographic analysis. Bond length analysis and theoretical calculations indicate that aromatic sextets are predominantly localized along the molecule's long axis. Significantly, [4]RB-Ar demonstrates narrow amplified spontaneous emission at around 834 nm when dispersed in polystyrene thin films. Moreover, solution-processed distributed feedback lasers employing [4]RB-Ar as the active gain material display tunable narrow emissions in the range of 830 to 844 nm.

In vitro biotransformation of 3-methylmethcathinone (3-MMC) through incubation with human liver microsomes and cytosol and application to in vivo samples.

Synthetic cathinones are the second largest group of new psychoactive substances (NPS) monitored by the European Monitoring Centre for Drugs and Drug Addiction. Although 3-methylmethcathinone (3-MMC, C11H15NO) is legally banned in many countries, it is readily available for purchase online and on the street. Due to the scarcity of information regarding the pharmacokinetic and toxicological profile of 3-MMC, understanding its biotransformation pathways is crucial in determining its potential toxicity in humans and in the development of analytical methods for screening of human matrices. To gain more insight, Phase I and Phase II in vitro biotransformation of 3-MMC was investigated using human liver microsomes and human liver cytosol. Suspect and non-target screening approaches were employed to identify metabolites. To confirm in vitro results in an in vivo setting, human matrices (i.e., plasma, urine, saliva and hair) positive for 3-MMC (n=31) were screened. In total three biotransformation products were identified in vitro: C11H15NO2 (a hydroxylated derivate), C11H17NO (a keto-reduced derivate) and C10H13NO (an N-desmethyl derivate). All three were confirmed as human metabolites in respectively 16 %, 52 % and 42 % of the analysed human samples. In total, 61 % of the analysed samples were positive for at least one of the three metabolites. Interestingly, three urine samples were positive for all three metabolites. The presence of 3-MMC in saliva and hair indicates its potential applicability in specific settings, e.g., roadside testing or chronic consumption analysis. To our knowledge, C11H17NO was not detected before in vivo. Although some of these metabolites have been previously suggested in vitro or in a single post mortem case report, a wide in vivo confirmation including the screening of four different human matrices was performed for the first time. These metabolites could serve as potential human biomarkers to monitor human 3-MMC consumption effectively.

Wastewater-based epidemiology methodology to investigate human exposure to bisphenol A, bisphenol F and bisphenol S.

Wastewater-based epidemiology (WBE) has become an invaluable tool for tracking the evolution of use or exposure of/to numerous substances. Bisphenols, commonly utilized in manufacturing plastic goods, have been categorized as endocrine disrupting chemicals, underscoring the critical need for real-time data on their local-level exposure to safeguard public health. In this study, we have developed a novel analytical method and WBE framework for the assessment of population-level exposure to bisphenol A (BPA) and its most prominent substitutes, bisphenols F and S (BPF and BPS), through the determination their Phase II metabolites in wastewater by WBE. Stability and exclusivity tests denoted that glucuronides are not stable in sewage, whereas sulfate metabolites are good biomarkers. Therefore, a solid-phase extraction followed by liquid chromatography-tandem mass spectrometry method was developed for the bisphenols' monosulfates and BPA bissulfate. The analytical method was validated with three different wastewater matrices, providing trueness (as recovery) in the 79-112 % range with relative standard deviations < 12 %, and method quantification limits below 2 ng L-1 for monosulfates, but higher (35 ng L-1) for BPA bissulfate. Subsequently, the method was applied to 24h-composite raw wastewater samples collected over a week in 4 different locations in Spain and Portugal. BPA bissulfate was not detected, but the three monosulfate metabolites of each bisphenol were positively detected in the samples, being the metabolite of BPA the most prevalent, followed by those of BPF and BPS. Community-wide BPA intake was then estimated to be higher than the European Food Safety Agency (EFSA) tolerable daily intake (TDI) of 2 × 10-4 µg kg-1day-1 in all locations. In the case of BPF and BPS, there is not enough metabolism data or even established limit, but they would also surpass safe levels in several locations if a similar metabolism and TDI would be assumed. This innovative method could be used to a larger set of wastewater-treatment plants as an early-warning approach on human exposure to bisphenols.

Determination of the urinary concentrations of six bisphenols in public servants by online solid-phase extraction-liquid chromatography tandem mass spectrometry.

Bisphenols are widely used as monomers and additives in plastic production. Thus, bisphenol A (BPA) and its most prominent substitutes have been detected in many environmental and human samples. This study proposes an online solid-phase extraction analytical methodology coupled to liquid chromatography with tandem mass spectrometry for the determination of six bisphenols (BPA and bisphenols F (BPF), S (BPS), AF (BPAF), B (BPB), and E (BPE)) in urine samples as an efficient and automated methodology. The method was developed and validated for all bisphenols with good recoveries (92-112%) and repeatability (RSD ≤ 10%) despite the variable matrix effects, except BPAF (which would require a dedicated internal standard), achieving method quantification limits in the 0.05-2.2 ng mL-1 range. The methodology was subsequently applied to 435 urine samples from a non-occupational exposure population (civil servants for the regional government) from Santiago de Compostela (Galicia, Spain). Only BPA, BPF, and BPS were positively detected; the last two presented higher detection frequencies than BPA. When the urinary concentrations are extrapolated to human intake and compared to the European Food Safety Agency (EFSA) tolerable daily intake (TDI) of 2 × 10-4 µg kg-1 day-1 (TDI), all BPA positively identified samples would surpass this threshold. Although no TDI exists currently for the other two identified bisphenols, it is evident that human exposure to bisphenols should be limited. Finally, the results stratification by gender revealed higher levels of exposure to BPF in the women group.

Obtaining patient phenotypes in SARS-CoV-2 pneumonia, and their association with clinical severity and mortality.

BACKGROUND: There exists consistent empirical evidence in the literature pointing out ample heterogeneity in terms of the clinical evolution of patients with COVID-19. The identification of specific phenotypes underlying in the population might contribute towards a better understanding and characterization of the different courses of the disease. The aim of this study was to identify distinct clinical phenotypes among hospitalized patients with SARS-CoV-2 pneumonia using machine learning clustering, and to study their association with subsequent clinical outcomes as severity and mortality. METHODS: Multicentric observational, prospective, longitudinal, cohort study conducted in four hospitals in Spain. We included adult patients admitted for in-hospital stay due to SARS-CoV-2 pneumonia. We collected a broad spectrum of variables to describe exhaustively each case: patient demographics, comorbidities, symptoms, physiological status, baseline examinations (blood analytics, arterial gas test), etc. For the development and internal validation of the clustering/phenotype models, the dataset was split into training and test sets (50% each). We proposed a sequence of machine learning stages: feature scaling, missing data imputation, reduction of data dimensionality via Kernel Principal Component Analysis (KPCA), and clustering with the k-means algorithm. The optimal cluster model parameters -including k, the number of phenotypes- were chosen automatically, by maximizing the average Silhouette score across the training set. RESULTS: We enrolled 1548 patients, each of them characterized by 92 clinical attributes (d=109 features after variable encoding). Our clustering algorithm identified k=3 distinct phenotypes and 18 strongly informative variables: Phenotype A (788 cases [50.9% prevalence] - age ∼ 57, Charlson comorbidity ∼ 1, pneumonia CURB-65 score ∼ 0 to 1, respiratory rate at admission ∼ 18 min-1, FiO2 ∼ 21%, C-reactive protein CRP ∼ 49.5 mg/dL [median within cluster]); phenotype B (620 cases [40.0%] - age ∼ 75, Charlson ∼ 5, CURB-65 ∼ 1 to 2, respiration ∼ 20 min-1, FiO2 ∼ 21%, CRP ∼ 101.5 mg/dL); and phenotype C (140 cases [9.0%] - age ∼ 71, Charlson ∼ 4, CURB-65 ∼ 0 to 2, respiration ∼ 30 min-1, FiO2 ∼ 38%, CRP ∼ 152.3 mg/dL). Hypothesis testing provided solid statistical evidence supporting an interaction between phenotype and each clinical outcome: severity and mortality. By computing their corresponding odds ratios, a clear trend was found for higher frequencies of unfavourable evolution in phenotype C with respect to B, as well as more unfavourable in phenotype B than in A. CONCLUSION: A compound unsupervised clustering technique (including a fully-automated optimization of its internal parameters) revealed the existence of three distinct groups of patients - phenotypes. In turn, these showed strong associations with the clinical severity in the progression of pneumonia, and with mortality.

Exploring the potential of horse amendment for the remediation of HCHs-polluted soils.

This study assessed for the first time the bioremediation potential of an organic horse amendment in soils contaminated with solid wastes of the obsolete pesticide lindane (α-hexachlorocyclohexane (α-HCH) = 80 mg kg-1, ß-HCH = 40 mg kg-1, γ,δ,ε-HCH≈10 mg kg-1) searching for a self-sufficient bio-based economy. Four treatments were implemented: polluted (PS, ΣHCHs = 130 mg kg-1) and control (CS, ΣHCHs = 1.24 mg kg-1) soils and the respective amended soils (APS and ACS). A commercial amendment, coming from organic wastes, was used for soil biostimulation (5% dry weight), and the temporal evolution of the enzymatic activity (dehydrogenase, ß-glucosidase activity, phenoloxidase, arylamidase, phosphatase, and urease) and HCHs concentration of the soils was evaluated over 55 days under controlled humidity and temperature conditions. The horse amendment positively influenced the physicochemical properties of the soil by reducing pH (from 8.3 to 8) and increasing the organic matter (TOC from 0.5 to 3.3%) and nutrient content (P and NH4+ from 24.1 to 13.7 to 142.1 and 41.2 mg kg-1, respectively). Consequently, there was a notable enhancement in the soil biological activity, specifically in the enzymatic activity of dehydrogenase, phenol-oxidase, phosphatase, and urease and, therefore, in HCH degradation, which increased from <1 to 75% after the incubation period. According to the chlorine position on the cyclohexane ring, the following ranking has been found for HCHs degradation: ß-HCH (46%) < Îµ-HCH (57%) < α-HCH (91%) ≈ Î´-HCH (91%) < Î³-HCH (100%). Pentachlorocyclohexene (PCCH) and 1,2,4-trichlorobenzene (1,2,4-TCB) were identified as HCHs degradation metabolites and disappeared at the end of the incubation time. Although further research is required, these preliminary findings suggest that organic amendments represent a sustainable, harmless, and cost-effective biostimulation approach for remediating soils contaminated with recalcitrant HCHs, boosting the circular economy.

Continuous UV-C/H2O2 and UV-C/Chlorine applied to municipal secondary effluent and nanofiltration retentate: Removal of contaminants of emerging concern, ecotoxicity, and reuse potential.

As global effects of water scarcity raise concerns and environmental regulations evolve, contemporary wastewater treatment plants (WWTPs) face the challenge of effectively removing a diverse range of contaminants of emerging concern (CECs) from municipal effluents. This study focuses on the assessment of advanced oxidation processes (AOPs), specifically UV-C/H2O2 and UV-C/Chlorine, for the removal of 14 target CECs in municipal secondary effluent (MSE, spiked with 10 µg L-1 of each CEC) or in the subsequent MSE nanofiltration retentate (NFR, no spiking). Phototreatments were carried out in continuous mode operation, with a hydraulic retention time of 3.4 min, using a tube-in-tube membrane photoreactor. For both wastewater matrices, UV-C photolysis (3.3 kJ L-1) exhibited high efficacy in removing CECs susceptible to photolysis, although lower treatment performance was observed for NFR. In MSE, adding 10 mg L-1 of H2O2 or Cl2 enhanced treatment efficiency, with UV-C/H2O2 outperforming UV-C/Chlorine. Both UV-C/AOPs eliminated the chronic toxicity of MSE toward Chlorella vulgaris. In the NFR, not only was the degradation of target CECs diminished, but chronic toxicity to C. vulgaris persisted after both UV-C/AOPs, with UV-C/Chlorine increasing toxicity due to potential toxic by-products. Nanofiltration permeate (NFP) exhibited low CECs and microbial content. A single chlorine addition effectively controlled Escherichia coli regrowth for 3 days, proving NFP potential for safe reuse in crop irrigation (<1 CFU/100 mL for E. coli; <1 mg L-1 for free chlorine). These findings provide valuable insights into the applications and limitations of UV-C/H2O2 and UV-C/Chlorine for distinct wastewater treatment scenarios.

Caring for patients in the Covid era: Are the quality of life the same for doctors and nursing staff?

BACKGROUND: The Covid-19 pandemic has represented one of the most stressful events of recent times and has placed enormous psychological pressure on doctors and nurses. AIMS: The objective of this work is to evaluate the psychological impact of the Covid-19 outbreak on Spanish nurses and doctors, and to identify factors related to their mental health. METHODS: The study is a descriptive study and examined 812 doctors and 768 nurses. The dependent variables were health-related quality of life, anxiety, depression, perceived stress and insomnia. Participants completed the Health-related Quality of Life-Questionnaire, the Generalized Anxiety Disorder 7-item-Scale, the Patient Health Questionnaire-9, the Impact Event Scale-Revised, and the Insomnia Severity Index. Sociodemographic and Covid-related data were also recorded. Descriptive statistics, univariable analysis and multivariable linear regression models were used. RESULTS: A greater proportion of nurses than doctors suffered clinical anxiety, depression and insomnia (56.84 % vs 45.81 p-value<0.0001, 64.67 % vs 53.39 p-value<0.0001, and 23.04 % vs 18.02 p-value 0.01, respectively). Although in our study nurses were more likely to suffer clinical anxiety, stress and insomnia than doctors, our results nevertheless showed that there were no differences in terms of quality of life. Different factors related to mental health were identified for doctors and nurses. Nurses working in care homes or geriatric services (OR = 4.13, IC95% 1.71-9.99, p-value 0.002), and in services with greatest contact with Covid-19 patients (OR = 1.71,IC95% 1.10-2.68, p-value 0.02) were more likely to suffer depression. CONCLUSIONS: Our study confirms that doctors and nurses are at high risk of clinical anxiety, depression, stress or insomnia during the Covid-19 pandemic.

Investigation of in vitro biotransformation of tris (1-chloro-2-propyl) phosphate and confirmation in human urine.

Tris (1-chloro-2-propyl) phosphate (TCIPP) is one of the major organophosphate flame retardants present in the indoor and outdoor environment. Knowledge of biotransformation pathways is important to elucidate potential bioavailability and toxicity of TCIPP and to identify relevant biomarkers. This study aimed to identify TCIPP metabolites through in vitro human metabolism assays and finally to confirm these findings in urine samples from an occupationally exposed population to propose new biomarkers to accurately monitor exposure to TCIPP. TCIPP was incubated with human liver microsomes and human liver cytosol to identify Phase I and Phase II metabolites, by liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). Using a suspect-screening approach, the established biomarkers bis (1-chloro-2-propyl) hydrogen phosphate (BCIPP) and 1-hydroxy-2-propyl bis (1-chloro-2-propyl) phosphate (BCIPHIPP) were identified. In addition, carboxyethyl bis (1-chloro-2-propyl) phosphate (TCIPP-M1), bis (1-chloropropan-2-yl) (-oxopropan-2-yl) phosphate (TCIPP-M2) and 1-chloro-3-hydroxypropan-2-yl bis (1-chloropropan-2-yl) phosphate (TCIPP-M3) were identified. TCIPP-M2, an intermediate product, was not reported before in literature. In urine samples, apart from BCIPP and BCIPHIPP, TCIPP-M1 and TCIPP-M3 were identified for the first time. Interestingly, BCIPP showed the lowest detection frequency, likely due to the poor sensitivity for this compound. Therefore, TCIPP-M1 and TCIPP-M3 could serve as potential additional biomarkers to more efficiently monitor TCIPP exposure in humans.

Screening of organic chemicals associated to virgin low-density polyethylene microplastic pellets exposed to the Mediterranean Sea environment by combining gas chromatography and liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry.

In this work, organic chemicals associated with microplastics (MPs) exposed to a coastal anthropogenized environment for up to eight weeks have been screened for, in order to discern the (de)sorption dynamics of chemicals in the marine ecosystem. Low-density polyethylene (LDPE) pellets were studied since they represent primary MPs used by the plastic industry and a relevant input of MPs into the oceans. To maximize the coverage of chemicals that could be detected, both liquid and gas chromatography coupled to quadrupole-time-of-flight (GC-QTOF and LC-QTOF, respectively) were used. In the case of LC-QTOF, an electrospray ionization source was employed, and the compounds were investigated by combining suspect and non-target screening workflows. The GC-QTOF was equipped with an electron ionization source and compounds were screened in raw and derivatized (silylated) extracts by deconvolution and contrast to high- and low-resolution libraries. A total of 50 compounds of multifarious classes were tentatively identified. Among them, melamine and 2-ethylhexyl salicylate (EHS) were detected in the original MPs but were rapidly desorbed. Melamine was completely released into the marine environment, while EHS was partly released but a portion remained bound to the MPs. On the other hand, many other chemicals of both anthropogenic (e.g. phenanthrene or benzophenone) and natural origin (e.g. betaine and several fatty acids) accumulated onto MPs over time. Quantification of 12 unequivocally identified chemicals resulted into a total concentration of 810 µg/kg after MPs exposure for 8 weeks.

Cost-sensitive ordinal classification methods to predict SARS-CoV-2 pneumonia severity.

OBJECTIVE: To study the suitability of costsensitive ordinal artificial intelligence-machine learning (AIML) strategies in the prognosis of SARS-CoV-2 pneumonia severity. MATERIALS & METHODS: Observational, retrospective, longitudinal, cohort study in 4 hospitals in Spain. Information regarding demographic and clinical status was supplemented by socioeconomic data and air pollution exposures. We proposed AI-ML algorithms for ordinal classification via ordinal decomposition and for cost-sensitive learning via resampling techniques. For performance-based model selection, we defined a custom score including per-class sensitivities and asymmetric misprognosis costs. 260 distinct AI-ML models were evaluated via 10 repetitions of 5×5 nested cross-validation with hyperparameter tuning. Model selection was followed by the calibration of predicted probabilities. Final overall performance was compared against five well-established clinical severity scores and against a 'standard' (non-cost sensitive, non-ordinal) AI-ML baseline. In our best model, we also evaluated its explainability with respect to each of the input variables. RESULTS: The study enrolled n = 1548 patients: 712 experienced low, 238 medium, and 598 high clinical severity. d = 131 variables were collected, becoming d ' = 148 features after categorical encoding. Model selection resulted in our best-performing AI-ML pipeline having: a) no imputation of missing data, b) no feature selection (i.e. using the full set of d ' features), c) 'Ordered Partitions' ordinal decomposition, d) cost-based reimbalance, and e) a Histogram-based Gradient Boosting classifier. This best model (calibrated) obtained a median accuracy of 68.1% [67.3%, 68.8%] (95% confidence interval), a balanced accuracy of 57.0% [55.6%, 57.9%], and an overall area under the curve (AUC) 0.802 [0.795, 0.808]. In our dataset, it outperformed all five clinical severity scores and the 'standard' AI-ML baseline. DISCUSSION & CONCLUSION: We conducted an exhaustive exploration of AI-ML methods designed for both ordinal and cost-sensitive classification, motivated by a real-world application domain (clinical severity prognosis) in which these topics arise naturally. Our model with the best classification performance exploited successfully the ordering information of ground truth classes, coping with imbalance and asymmetric costs. However, these ordinal and cost-sensitive aspects are seldom explored in the literature.

Borolatonin limits cognitive deficit and neuron loss while increasing proBDNF in ovariectomised rats.

BACKGROUND: Borolatonin is a potential therapeutic agent for some neuronal diseases such as Alzheimer's disease (AD). Its administration exerts ameliorative effects such as those induced by the equimolar administration of melatonin in behavioral tests on male rats and in neuronal immunohistochemistry assays. OBJECTIVE: In this study, motivated by sex differences in neurobiology and the incidence of AD, the ability of borolatonin to induce changes in female rats was assessed. METHODS: Effects of borolatonin were measured by the evaluation of both behavioral and immunohistopathologic approaches; additionally, its ability to limit amyloid toxicity was determined in vitro. RESULTS: Surprisingly, behavioral changes were similar to those reported in male rats, but not those evaluated by immunoassays regarding neuronal survival; while pro-brain-derived neurotrophic factor (BDNF) immunoreactivity and the limitation of toxicity by amyloid in vitro were observed for the first time. CONCLUSION: Borolatonin administration induced changes in female rats. Differences induced by the administration of borolatonin or melatonin could be related to the differences in the production of steroid hormones in sex dependence. Further studies are required to clarify the possible mechanism and origin of differences in disturbed memory caused by the gonadectomy procedure between male and female rats.

Influence of physical activity on the prognosis of COPD patients: the HADO.2 score - health, activity, dyspnoea and obstruction.

Objective: The aim of this study was to create a prognostic instrument for COPD with a multidimensional perspective that includes physical activity (PA). The score also included health status, dyspnoea and forced expiratory volume in 1 s (HADO.2 score). Methods: A prospective, observational, non-intervention study was carried out. Patients were recruited from the six outpatient clinics of the respiratory service of a single university hospital. The component variables of the HADO.2 score and BODE index were studied, and PA was measured using an accelerometer. The outcomes for the HADO.2 score were mortality and hospitalisations during follow-up and an exploration of the correlation with health-related quality of life at the moment of inclusion in the study. Results: 401 patients were included in the study and followed up for three years. The HADO.2 score showed good predictive capacity for mortality: C-index 0.79 (0.72-0.85). The C-index for hospitalisations was 0.72 (0.66-0.77) and the predictive ability for quality of life, as measured by R2, was 0.63 and 0.53 respectively for the Saint George's Respiratory Questionnaire and COPD Assessment Test. Conclusions: There was no statistically significant difference between the mortality predictive capacity of the HADO.2 score and the BODE index. Adding PA to the original BODE index significantly improved the predictive capacity of the index. The HADO.2 score, which includes PA as a key variable, showed good predictive capacity for mortality and hospitalisations. There were no differences in the predictive capacity of the HADO.2 score and the BODE index.

IL-6, IL-10 and TNF-α gene polymorphisms in preeclampsia: a case-control study in a Mexican population.

OBJECTIVES: We focused our study on examining the genotype and allele frequency of IL-6 (rs1800795), TNF-α (rs1800629) and IL-10 (rs1800872) single nucleotide polymorphisms (SNP) on preeclampsia (PE) diagnosed Mexican pregnant women. MATERIAL AND METHODS: A case-control study was designed including 86 preeclampsia patients and 100 normotensives pregnancies from Women's Hospital of Culiacan, Mexico. Genotyping of IL-6, TNF-α and IL-10 was performed using TaqMan SNP Genotyping. RESULTS: Not significant association was found between development of PE and genotypic (p > 0.05) and allelic (p > 0.05) frequencies of IL-6, TNF-α and IL-10 SNPs. Genotype distributions of IL-6 (p = 0.599), TNF-α (p = 0.721) and IL-10 (p = 0.761) polymorphisms in the two groups were in agreement with Hardy-Weinberg equilibrium. CONCLUSIONS: According to the findings, the IL-6, TNF-α and IL-10 SNPs are not exponents of susceptibility to developing PE.

Incidencia del espectro de acretismo placentario en la unidad de cuidados intensivos obstétricos del Hospital de la Mujer de Sinaloa / Incidence of the placental accretism spectrum in the obstetric intensive care unit of the Hospital de la Mujer of Sinaloa

Resumen OBJETIVO: Determinar la incidencia del espectro del acretismo placentario en pacientes ingresadas a la unidad de cuidados intensivos obstétricos del Hospital de la Mujer, Culiacán, Sinaloa. MATERIALES Y MÉTODOS: Estudio retrospectivo, transversal y descriptivo fundamentado en el análisis de la base de datos del Hospital de la Mujer de pacientes internadas entre los años 2017 a 2020 con diagnóstico de espectro de placenta acreta, referidas o diagnosticadas en la institución e intervenidas para histerectomía por la complicación estudiada. RESULTADOS: Se analizaron 22 pacientes con diagnóstico de acretismo placentario que dieron una incidencia de 0.09%; de éstas, a 1 se le indicó cesárea; 19 de las 22 pacientes tenían antecedente de cicatriz uterina previa, todas con placenta previa. El promedio de edad fue de 30.86 ± 4 años. La cesárea se practicó, en promedio, a las 34 semanas de embarazo con dos técnicas quirúrgicas. El sangrado promedio estimado fue de 1.947 mL. Las complicaciones transoperatorias fueron las lesiones: ureteral (n = 2) y vesical (n = 1). La principal complicación posoperatoria fue la fístula vesicouterina (n = 1). El promedio de estancia fue de 2 días en 16 de las 22 pacientes y de 7 días en las 6 restantes. CONCLUSIONES: Lo importante del acretismo placentario es el diagnóstico oportuno que permita derivar a las pacientes a centros hospitalarios que cuenten con especialistas experimentados en la atención de estos casos.

Abstract OBJECTIVE: To determine the incidence of placental accretism spectrum in pregnant women admitted to the obstetric intensive care unit of the Hospital de la Mujer, Culiacán, Sinaloa. MATERIALS AND METHODS: Retrospective, cross-sectional, descriptive study based on the analysis of the database of the Hospital de la Mujer of patients admitted between 2017 and 2020 with a diagnosis of placenta accreta spectrum, referred or diagnosed at the institution and underwent hysterectomy for the complication studied. RESULTS: Twenty-two patients with a diagnosis of placenta accreta were analysed, giving a prevalence of 0.09%; of these, caesarean section was indicated in 0.2%. 19 of the 22 patients had a history of previous uterine scarring, all with placenta praevia. Mean age was 30.86 ± 4 years. Caesarean section was performed at a mean gestational age of 34 weeks using two surgical techniques. The mean estimated blood loss was 1,947 mL. The most common operative complications were ureteral (n = 2) and bladder (n = 1) injuries. The most common postoperative complication was vesico-uterine fistula (n = 1). The mean length of stay was 2 days in 16 of the 22 patients and 7 days in the remaining 6 patients. CONCLUSIONS: The most important aspect of placenta accreta is early diagnosis, which allows referral to hospital centres with specialists experienced in the management of these cases.