Impact of Potentially Toxic Compounds in Cow Milk: How Industrial Activities Affect Animal Primary Productions

Potentially toxic elements (PTEs) and polycyclic aromatic hydrocarbons (PAHs) frequently coexist in soils near industrial areas and sometimes in environmental compartments directly linked to feed (forage) and food (milk) production. However, the distribution of these pollutants along the dairy farm production chain is unclear. Here, we analyzed soil, forage, and milk samples from 16 livestock farms in Spain: several PTEs and PAHs were quantified. Farms were compared in terms of whether they were close to (5 km) industrial areas. The results showed that PTEs and PAHs were enriched in the soils and forages from farms close to industrial areas, but not in the milk. In the soil, the maximum concentrations of PTEs reached 141, 46.1, 3.67, 6.11, and 138 mg kg-1 for chromium, arsenic, cadmium, mercury, and lead, respectively, while fluoranthene (172.8 µg kg-1) and benzo(b)fluoranthene (177.4 µg kg-1) were the most abundant PAHs. Principal component analysis of the soil PTEs suggested common pollution sources for iron, arsenic, and lead. In the forage, the maximum contents of chromium, arsenic, cadmium, mercury, and lead were 32.8, 7.87, 1.31, 0.47, and 7.85 mg kg-1, respectively. The PAH found in the highest concentration in the feed forage was pyrene (120 µg kg-1). In the milk, the maximum PTE levels were much lower than in the soil or the feed forages: 74.1, 16.1, 0.12, 0.28, and 2.7 µg kg-1 for chromium, arsenic, cadmium, mercury, and lead, respectively. Neither of the two milk samples exceeded the 20 µg kg-1 limit for lead set in EU 1881/2006. Pyrene was the most abundant PAH found in the milk (39.4 µg kg-1), while high molecular weight PAHs were not detected. For PTEs, the results showed that soil-forage transfer factors were higher than forage-milk ratios. Our results suggest that soils and forages around farms near industries, as well as the milk produced from those farms, have generally low levels of PTE and PAH contaminants.This research was funded by the Spanish Ministry of Science and Innovation (PID2020- 117282RB-I00, MCI-20-PID2019-000081, PID2019-109698GB-I00, PID2021-126010OR-I00), and by Principado de Asturias Regional Government co-financed by the European Union through the European Regional Development Fund (grants IDI/2021/000081 and IDI/2021/000102). S.F. received an FPI fellowship (grant BES-2017-081314) supported by MCIN/AEI/10.13039/501100011033 and the Investments for the Future program of the European Social Fund, “El FSE invierte en tu futuro”

Melatonin decreases glucose metabolism in prostate cancer cells: A 13C stable isotope-resolved metabolomic study

The pineal neuroindole melatonin exerts an exceptional variety of systemic functions. Some of them are exerted through its specific membrane receptors type 1 and type 2 (MT1 and MT2) while others are mediated by receptor-independent mechanisms. A potential transport of melatonin through facilitative glucose transporters (GLUT/SLC2A) was proposed in prostate cancer cells. The prostate cells have a particular metabolism that changes during tumor progression. During the first steps of carcinogenesis, oxidative phosphorylation is reactivated while the switch to the “Warburg effect” only occurs in advanced tumors and in the metastatic stage. Here, we investigated whether melatonin might change prostate cancer cell metabolism. To do so, 13C stable isotope-resolved metabolomics in androgen sensitive LNCaP and insensitive PC-3 prostate cancer cells were employed. In addition to metabolite 13C-labeling, ATP/AMP levels, and lactate dehydrogenase or pentose phosphate pathway activity were measured. Melatonin reduces lactate labeling in androgen-sensitive cells and it also lowers 13C-labeling of tricarboxylic acid cycle metabolites and ATP production. In addition, melatonin reduces lactate 13C-labeling in androgen insensitive prostate cancer cells. Results demonstrated that melatonin limits glycolysis as well as the tricarboxylic acid cycle and pentose phosphate pathway in prostate cancer cells, suggesting that the reduction of glucose uptake is a major target of the indole in this tumor type

Goat milk exosomes as natural nanoparticles for detecting inflammatory processes by optical imaging

Exosomes are cell-derived nanovesicles with a proven intercellular signaling role in inflammation processes and immune response. Due to their natural origin and liposome-like structure, these nanometer-scale vesicles have emerged as novel platforms for therapy and diagnosis. In this work, goat milk exosomes are isolated and fully characterized in terms of their physicochemical properties, proteomics, and biochemical profile in healthy mice, and used to detect inflammatory processes by optical imaging. For the in vitro and in vivo experiments, the exosomes are covalently labeled with the commercial fluorophores sulfo-Cyanine 5 and BODIPY-FL to create nanoprobes. In vitro studies using confocal imaging, flow cytometry, and colorimetric assays confirm the internalization of the nanoprobes as well their lack of cytotoxicity in macrophage populations RAW 264.7. Optical imaging in the mouse peritoneal region confirms the in vivo ability of one of the nanoprobes to localize inflammatory processes. In vivo imaging shows exosome uptake in the inflamed peritoneal region, and flow-cytometric analysis of peritonitis exudates confirms the uptake by macrophage and neutrophil populations. These results support the promising use of goat milk exosomes as natural probes in the detection of inflammatory processes.This study has been funded by Instituto de Salud Carlos III, through the project "PI20/01632", co-funded by European Regional Development Fund (ERDF), "A way to make Europe" and by Comunidad de Madrid, project "Y2018/NMT-4949 (NanoLiver-CM)" and "S2017/BMD-3867 (RENIM-CM)", co-funded by European Structural and Investment Fund. This work has been also supported by "Diagnosis and treatment follow-up of severe Staphylococcal Infections with Anti-Staphylococcal antibodies and Immune-PET - Grant Fundación BBVA a Equipos de Investigación Científica 2018". A. Santos-Coquillat is grateful for financial support to Consejería de Educación e Investigación, co-financed by European Social Fund (ESF) grant PEJD-2018-POST/BMD-9592. A. Santos Coquillat is also funded by Instituto de Salud Carlos III, co-funded by European Social Fund "Investing in your future" (grant CD19/00136). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation. The CNIO Proteomics Unit is funded by the H2020 project EPIC-XS (ref. 823839). Biomedical Imaging has been conducted at the Advanced Imaging Unit of the CNIC (Centro Nacional de Investigaciones Cardiovasculares Carlos III), Madrid, Spain

Criterios de ordenación temporal de las intervenciones quirúrgicas en patología cardiovascular y endovascular adquirida. Versión 2022

Waiting list management of cardiac surgical procedures is a main concern for all the Spanish autonomic health systems and for our scientific Society. The first statement for optimal timing of patients waiting for cardiac surgery was published in 2000. Since then, after significant changes in the management of some pathologies, new normative frameworks and the current healthcare situation, a review of the timing criteria to offer an adequate and updated standard of care is needed. In this document we aim to review the available literature in the field and stablish a consensus within a working group of the Spanish Society of Cardiovascular and Endovascular Surgery to optimize the priority recommendations in cardiac surgical waiting lists in our country. (c) 2022 Sociedad Espanola de Cirugia Cardiovascular y Endovascular. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ riccuses/by-nc-nri/4.0/)

Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment

Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Classification of follicular-patterned thyroid lesions using a minimal set of epigenetic biomarkers

[Objective]: The minimally invasive fine-needle aspiration cytology (FNAC) is the current gold standard for the diagnosis of thyroid nodule malignancy. However, the correct discrimination of follicular neoplasia often requires more invasive diagnostic techniques. The lack of suitable immunohistochemical markers to distinguish between follicular thyroid carcinoma and other types of follicular-derived lesions complicates diagnosis, and despite most of these tumours being surgically resected, only a small number will test positive for malignancy. As such, the development of new orthogonal diagnostic approaches may improve the accuracy of diagnosing thyroid nodules.[Design]: This study includes a retrospective, multi-centre training cohort including 54 fresh-frozen follicular-patterned thyroid samples and two independent, multi-centre validation cohorts of 103 snap-frozen biopsies and 33 FNAC samples, respectively.[Methods]: We performed a genome-wide genetic and epigenetic profiling of 54 fresh-frozen follicular-patterned thyroid samples using exome sequencing and the Illumina Human DNA Methylation EPIC platform. An extensive validation was performed using the bisulfite pyrosequencing technique.[Results]: Using a random forest approach, we developed a three-CpG marker-based diagnostic model that was subsequently validated using bisulfite pyrosequencing experiments. According to the validation cohort, this cost-effective method discriminates between benign and malignant nodules with a sensitivity and specificity of 97 and 88%, respectively (positive predictive value (PPV): 0.85, negative predictive value (NPV): 0.98).[Conclusions]: Our classification system based on a minimal set of epigenetic biomarkers can complement the potential of the diagnostic techniques currently available and would prioritize a considerable number of surgical interventions that are often performed due to uncertain cytology.[Significance statement]: In recent years, there has been a significant increase in the number of people diagnosed with thyroid nodules. The current challenge is their etiological diagnosis to discount malignancy without resorting to thyroidectomy. The method proposed here, based on DNA pyrosequencing assays, has high sensitivity (0.97) and specificity (0.88) for the identification of malignant thyroid nodules. This simple and cost-effective approach can complement expert pathologist evaluation to prioritize the classification of difficult-to-diagnose follicular-patterned thyroid lesions and track tumor evolution, including real-time monitoring of treatment efficacy, thereby stimulating adherence to health promotion programs.Peer reviewe

Level TE9c of Sima del Elefante (Sierra de Atapuerca, Spain): A comprehensive approach

Level TE9c of the Sima del Elefante site (Sierra de Atapuerca, Spain) is one of the oldest sites with evidence of human occupation in western Europe. We began excavating level TE9c in 2003, and the work there continues today. The studies of the archaeology, palaeontology and geology from this locality have provided an indispensable dataset with which to capture a picture in the scenario of the origin of humans in Europe. Based on these data, we raise and discuss several topics, such as the possible origin of the lineage of the first hominins that inhabited western Europe; their capacity to have active hunting or scavenging abilities; whether their subsistence strategies were successful; and what the environment and habitats where these hominin groups settled was like. The aim of this paper is to present the results and discussions obtained from the research team and to establish the primary features of early human occupations in southwestern Europe. Tentatively, we may conclude, based on the events recorded at TE9c, that the first humans were in the Iberian peninsula at around 1.2 Ma they used the caves of the Sierra de Atapuerca as shelters probably during their hunting activities; the cavities were surrounded by Mediterranean forest, rivers and water ponds, and varied habitats as suggested by the rich and diverse assemblage of fossils of vertebrates (fish, amphibians and reptiles, birds, large and small mammals); where humans possibly caught what they found in the surroundings