Desarrollo de nuevas estrategias de microextracción. Aplicación a la determinación de filtros UV en muestras de agua de interés medioambiental

Las técnicas de microextracción aportan numerosas ventajas a la etapa de preparación de la muestra. Algunas de estas técnicas están actualmente bien establecidas y se han implementado en numerosos laboratorios analíticos, aunque también se han descrito algunas limitaciones. En la presente Tesis Doctoral se ha contribuido al desarrollo y validación de nuevas estrategias analíticas basadas en técnicas de microextracción, y se han aportado algunas mejoras a las ya existentes, obteniéndose buenas características como rapidez, bajo coste, simplicidad y respeto hacia el medio ambiente y el operador (“Química Verde”). Para evaluar la aplicabilidad de estas nuevas estrategias, se han aplicado a la determinación de “Filtros UV” en muestras de agua. Debe señalarse que los filtros UV son un grupo de ingredientes cosméticos ampliamente utilizados en productos para la protección solar, además de en otros productos cosméticos de uso cotidiano. Estos ingredientes cosméticos se han catalogado como contaminantes emergentes, ya que pueden provocar efectos adversos en el medio ambiente acuático, al que llegan con relativa facilidad. Es por ello que resulta interesante su determinación. Esta Tesis Doctoral se ha estructurado en siete capítulos. La Sección I, constituida por los Capítulos 1 y 2, corresponde a la Introducción, en la que se describen algunos conceptos fundamentales, los antecedentes del tema y las metodologías analíticas seguidas en la presente Tesis Doctoral. En este sentido: • En el Capítulo 1 se resume la evolución que han sufrido las técnicas de microextracción, mencionando las ventajas e incovenientes de cada una de ellas, y presentando las aportaciones realizadas en esta Tesis Doctoral sobre el desarrollo de nuevas técnicas de microextracción • En el Capítulo 2 se incluye información general sobre los filtros UV, incluyendo su clasificación y su empleo en los productos cosméticos. También se discute su presencia en el cuerpo humano y, especialmente, en el medioambiente, y se realiza una revisión exhaustiva de los métodos analíticos empleados para la determinación de filtros UV en muestras de agua de origen medioambiental, dado que es el tema de la presente Tesis Doctoral En los cinco capítulos incluidos en la Sección II se recoge el trabajo experimental, así como los resultados obtenidos a lo largo de esta Tesis Doctoral. Al final de cada capítulo se exponen las conclusiones más relevantes obtenidas en cada uno de los estudios realizados. • En el Capítulo 3 se describe un método analítico, basado en la microextracción líquido-líquido dispersiva, que permite la determinación del contenido total de filtros UV en muestras de agua de mar, determinándolos tanto en la fracción soluble como en la materia particulada • En el Capítulo 4 se presenta una nueva técnica de microextracción basada en la formación in situ de un agregado supramolecular como fase de extracción • En los Capítulos 5 a 7 se desarrolla una nueva técnica de microextracción mediada por materiales magnéticos como fase de extracción, siendo validada mediante la determinación de filtros UV lipofílicos e hidrofílicos en muestras de agua de origen medioambiental de diferente naturaleza Cabe mencionar que el trabajo incluido en el Capítulo 4 fue realizado en una estancia predoctoral de cuatro meses en el Departamento de Química de la Universidad de Ioannina (Grecia) bajo la supervisión del Prof. Dimosthenis L. Giokas. Para finalizar, se presentan las Conclusiones generales de esta Tesis Doctoral y, como Anexo, se incluyen las publicaciones científicas a las que ha dado lugar.Microextraction techniques provide numerous advantages to sample preparation step. Some of these techniques can nowadays be considered well established and have been implemented in many analytical laboratories, although some limitations have been also described. In this PhD thesis, new analytical strategies based on microextraction techniques have been developed and evaluated based on their analytical characteristics. These methods offers many advantages to sample preparation including simplicity, rapid analysis time, cost-effectiveness and being both user and environmentally friendly according to the so-called “Green Chemistry”. These novel approaches have been applied to the determination of “UV filters” in water samples. It should be said that UV filters are a group of cosmetic ingredients nowadays used in many cosmetic products, in addition to those exclusively designed for sun protection (i.e. sunscreens). These cosmetic ingredients have been catalogued as emergent contaminants since they could cause harmful effects on the aquatic environment. In these sense, their determination is of high interest. This PhD thesis is divided into seven chapters. Some fundamental concepts, the background of the topic and the methodologies used in this PhD thesis are described in Section I, Introduction. In this sense: • The evolution of the microextraction techniques, their advantages and limitations and the contributions of this PhD thesis to the development of new microextraction techniques are summarized in Chapter 1 • General information about UV filters, their classification and their use in cosmetic products are included in Chapter 2. Moreover, their presence in the human body as well as in the environment, and an exhaustive compilation of analytical methods employed to the determination of UV filters in environmental water samples are also included in this chapter The experimental work and the results obtained along this PhD thesis are presented in Section II. The most relevant conclusions of each study are presented at the end of each chapter. • A method to determine UV filters not only in the soluble fraction but also in the particulate fraction (i.e. that adhered to suspended particles) of seawater samples, based on dispersive liquid-liquid microextraction, is described in Chapter 3 • A new microextraction technique based on the in situ formation of a supramolecular aggregate as extractant phase is presented in Chapter 4 • A novel microextraction technique mediated by magnetic materials as extractant phase is developed in Chapters 5 to 7 It should be point out that the work included in Chapter 4 was carried out in a pre-doctoral stay for four months in the Department of Chemistry of the University of Ioannina (Greece) under the supervision of Prof. Dismothenis L. Giokas. Finally, the General conclusions of this doctoral thesis are shown and the published articles obtained from the work performed in this PhD thesis are included as Annex

Low toxicity deep eutectic solvent-based ferrofluid for the determination of UV filters in environmental waters by stir bar dispersive liquid microextraction.

[EN] In this work, a low toxicity deep eutectic solvent-based ferrofluid is presented for the first time as magnetic fluid to be used as an efficient solvent in liquid-based microextraction techniques. This ferrofluid is made of a hydrophobic deep eutectic solvent, composed by menthol and thymol in a 1:5 molar ratio as carrier solvent, and oleic acid-coated cobalt ferrite (CoFe2O4@oleic acid) magnetic nanoparticles. This material was characterized via magnetism measurement, scanning electron microscopy, infrared spectroscopy and density measurement. The determination of UV filters in environmental water samples was selected as model analytical application to test the extraction performance of this new ferrofluid by employing stir bar dispersive liquid microextraction, prior to liquid chromatography-tandem mass spectrometry analysis. The response surface methodology was used as a multivariate optimization method for extraction step. Under the optimized conditions, good analytical features were obtained, such as low limits of detection between 7 and 83ngL-1, good repeatability (relative standard deviations, RSD (%) below 15%), enrichment factors between 46 and 101 and relative recoveries between 80 and 117%, proving the good extraction capability of this ferrofluid. Finally, the method was successfully applied to three environmental waters (beach and river waters), finding trace amounts of the target UV filters. The presented low toxicity deep eutectic solvent-based ferrofluid results to be a good alternative to conventional solvents used in liquid-phase microextraction techniques.J.L.B. thanks the Generalitat Valenciana and the European Social Fund for his postdoctoral grant, and A.D. thanks the Basque Country Government for her predoctoral contract (Bikaintek 2020 Program from the Regional Minister for Economic Development and Infrastructures (order 2021–1353, file number 021-B2/2020)). Authors also thank to the Magnetism Unit of SGIker of University of Basque Country (UPV/EHU) for kindly carrying out the magnetism measurements. This article is based upon work from the National Thematic Network on Sample Treatment (RED-2018-102522-T) of the Spanish Ministry of Science, Innovation and Universities, and the Sample Preparation Study Group and Network supported by the Division of Analytical Chemistry of the European Chemical Society

The outcome of boosting mitochondrial activity in alcohol-associated liver disease is organ-dependent.

BACKGROUND AND AIMS Alcohol-associated liver disease (ALD) accounts for 70% of liver-related deaths in Europe, with no effective approved therapies. Although mitochondrial dysfunction is one of the earliest manifestations of alcohol-induced injury, restoring mitochondrial activity remains a problematic strategy due to oxidative stress. Here, we identify methylation-controlled J protein (MCJ) as a mediator for ALD progression and hypothesize that targeting MCJ may help in recovering mitochondrial fitness without collateral oxidative damage. APPROACH AND RESULTS C57BL/6 mice [wild-type (Wt)] Mcj knockout and Mcj liver-specific silencing (MCJ-LSS) underwent the NIAAA dietary protocol (Lieber-DeCarli diet containing 5% (vol/vol) ethanol for 10 days, plus a single binge ethanol feeding at day 11). To evaluate the impact of a restored mitochondrial activity in ALD, the liver, gut, and pancreas were characterized, focusing on lipid metabolism, glucose homeostasis, intestinal permeability, and microbiota composition. MCJ, a protein acting as an endogenous negative regulator of mitochondrial respiration, is downregulated in the early stages of ALD and increases with the severity of the disease. Whole-body deficiency of MCJ is detrimental during ALD because it exacerbates the systemic effects of alcohol abuse through altered intestinal permeability, increased endotoxemia, and dysregulation of pancreatic function, which overall worsens liver injury. On the other hand, liver-specific Mcj silencing prevents main ALD hallmarks, that is, mitochondrial dysfunction, steatosis, inflammation, and oxidative stress, as it restores the NAD + /NADH ratio and SIRT1 function, hence preventing de novo lipogenesis and improving lipid oxidation. CONCLUSIONS Improving mitochondrial respiration by liver-specific Mcj silencing might become a novel therapeutic approach for treating ALD.This work was supported by grants from Ministerio de Ciencia e Innovación, Programa Retos-Colaboración RTC2019-007125-1 (for Jorge Simon and Maria Luz Martinez-Chantar); Ministerio de Economía, Industria y Competitividad, Retos a la Sociedad AGL2017- 86927R (for F.M.); Instituto de Salud Carlos III, Proyectos de Investigación en Salud DTS20/00138 and DTS21/00094 (for Jorge Simon and Maria Luz Martinez-Chantar, and Asis Palazon. respectively); Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias co-founded by European Regional Development Fund/European Social Fund, “Investing in your future” PI19/00819, “Una manera de hacer Europa” FIS PI20/00765, and PI21/01067 (for Jose J. G. Marin., Pau Sancho-Bru,. and Mario F. Fraga respectively); Departamento de Industria del Gobierno Vasco (for Maria Luz Martinez-Chantar); Asturias Government (PCTI) co-funding 2018-2023/ FEDER IDI/2021/000077 (for Mario F. Fraga.); Ministerio de Ciencia, Innovación y Universidades MICINN: PID2020-117116RB-I00, CEX2021-001136-S PID2020-117941RB-I00, PID2020-11827RB-I00 and PID2019-107956RA-100 integrado en el Plan Estatal de Investigación Científica y Técnica y Innovación, cofinanciado con Fondos FEDER (for Maria Luz Martinez-Chantar, Francisco J Cubero., Yulia A Nevzorova and Asis Palazon); Ayudas Ramón y Cajal de la Agencia Estatal de Investigación RY2013-13666 and RYC2018- 024183-I (for Leticia Abecia and Asis Palazon); European Research Council Starting Grant 804236 NEXTGEN-IO (for Asis Palazon); The German Research Foundation SFB/TRR57/P04, SFB1382-403224013/ A02 and DFG NE 2128/2-1 (for Francisco J Cubero and Yulia A Nevzorova); National Institute of Health (NIH)/National Institute of Alcohol Abuse and Alcoholism (NIAAA) 1U01AA026972-01 (For Pau Sancho-Bru); Junta de Castilla y León SA074P20 (for Jose J. G. Marin); Junta de Andalucía, Grupo PAIDI BIO311 (for Franz Martin); CIBERER Acciones Cooperativas y Complementarias Intramurales ACCI20-35 (for Mario F. Fraga); Ministerio de Educación, Cultura y Deporte FPU17/04992 (for Silvia Ariño); Fundació Marato TV3 201916-31 (for Jose J. G. Marin.); Ainize Pena-Cearra is a fellow of the University of the Basque Country (UPV/ EHU); BIOEF (Basque Foundation for Innovation and Health Research); Asociación Española contra el Cáncer (Maria Luz Martinez-Chantar and Teresa C. Delgado.); Fundación Científica de la Asociación Española Contra el Cáncer (AECC Scientific Foundation) Rare Tumor Calls 2017 (for Maria Luz Martinez-Chantar); La Caixa Foundation Program (for Maria Luz Martinez-Chantar); Proyecto Desarrollo Tecnologico CIBERehd (for Maria Luz Martinez-Chantar); Ciberehd_ISCIII_MINECO is funded by the Instituto de Salud Carlos III.S

Frequency and management of maternal infection in health facilities in 52 countries (GLOSS): a 1-week inception cohort study

Background Maternal infections are an important cause of maternal mortality and severe maternal morbidity. We report the main findings of the WHO Global Maternal Sepsis Study, which aimed to assess the frequency of maternal infections in health facilities, according to maternal characteristics and outcomes, and coverage of core practices for early identification and management. Methods We did a facility-based, prospective, 1-week inception cohort study in 713 health facilities providing obstetric, midwifery, or abortion care, or where women could be admitted because of complications of pregnancy, childbirth, post-partum, or post-abortion, in 52 low-income and middle-income countries (LMICs) and high-income countries (HICs). We obtained data from hospital records for all pregnant or recently pregnant women hospitalised with suspected or confirmed infection. We calculated ratios of infection and infection-related severe maternal outcomes (ie, death or near-miss) per 1000 livebirths and the proportion of intrahospital fatalities across country income groups, as well as the distribution of demographic, obstetric, clinical characteristics and outcomes, and coverage of a set of core practices for identification and management across infection severity groups. Findings Between Nov 28, 2017, and Dec 4, 2017, of 2965 women assessed for eligibility, 2850 pregnant or recently pregnant women with suspected or confirmed infection were included. 70·4 (95% CI 67·7–73·1) hospitalised women per 1000 livebirths had a maternal infection, and 10·9 (9·8–12·0) women per 1000 livebirths presented with infection-related (underlying or contributing cause) severe maternal outcomes. Highest ratios were observed in LMICs and the lowest in HICs. The proportion of intrahospital fatalities was 6·8% among women with severe maternal outcomes, with the highest proportion in low-income countries. Infection-related maternal deaths represented more than half of the intrahospital deaths. Around two-thirds (63·9%, n=1821) of the women had a complete set of vital signs recorded, or received antimicrobials the day of suspicion or diagnosis of the infection (70·2%, n=1875), without marked differences across severity groups. Interpretation The frequency of maternal infections requiring management in health facilities is high. Our results suggest that contribution of direct (obstetric) and indirect (non-obstetric) infections to overall maternal deaths is greater than previously thought. Improvement of early identification is urgently needed, as well as prompt management of women with infections in health facilities by implementing effective evidence-based practices