24 research outputs found

    Los mamíferos salvajes terrestres como bioindicadores: nuevos avances en Ecotoxicología

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    Ecotoxicology as science pretends to correctly identify problems associated to the presence and the effect of chemical substances in the environmental and the wildlife. In this field, the presence of heavy metals on ecosystems constitutes a serious problem, for both their elevated environmental persistence and high toxicity for wildlife. In this sense, the present paper shows a review concerning more recent advances in the modern biomonitoring methodologies, using wild mammals and making differences between destructive and non-destructive methods. L’Ecotoxicologie comme science cherche identifier correcte des problèmes dérivés de la présence et effet des substances chimiques dans l’environnement et les êtres vivants. Dans ce domaine, la présence des métaux lourds dans les écosystèmes constitue un problème très sérieux, pour son élevé persistance environnementale et son haute toxicité pour tous les organismes vivants. Dans ce sens, le présent travaille fait une révision à propos des progrès dans les modernes méthodologies de biomonitoring, avec l’emploie des mammifères sauvages et en faisant une distinction à la méthodologie employee (méthodes destructives et non destructives).La Ecotoxicología como ciencia busca identificar adecuadamente los problemas derivados de la presencia y efecto de sustancias químicas en el medio ambiente y los seres vivos. Dentro de este campo, la presencia de metales pesados en los ecosistemas constituye un serio problema, tanto por su elevada persistencia medioambiental como por su alta toxicidad para todos los organismos vivos. En este sentido, el presente trabajo realiza una revisión sobre los avances más recientes ocurridos en las modernas metodologías de biomonitorización, empleando para ello mamíferos salvajes y haciendo distinción en la metodología empleada (métodos destructivos y no destructivos)

    Discovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs in hematological malignancies

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    The indisputable role of epigenetics in cancer and the fact that epigenetic alterations can be reversed have favoured development of epigenetic drugs. In this study, we design and synthesize potent novel, selective and reversible chemical probes that simultaneously inhibit the G9a and DNMTs methyltransferase activity. In vitro treatment of haematological neoplasia (acute myeloid leukaemia-AML, acute lymphoblastic leukaemia-ALL and diffuse large B-cell lymphoma-DLBCL) with the lead compound CM-272, inhibits cell proliferation and promotes apoptosis, inducing interferon-stimulated genes and immunogenic cell death. CM-272 significantly prolongs survival of AML, ALL and DLBCL xenogeneic models. Our results represent the discovery of first-in-class dual inhibitors of G9a/DNMTs and establish this chemical series as a promising therapeutic tool for unmet needs in haematological tumours.We particularly acknowledge the Biobank of the University of Navarra for its collaboration. We thank Dr Edorta Martínez de Marigorta and Dr Francisco Palacios from Departamento de Química Orgánica I, Facultad de Farmacia, Universidad del Pais Vasco for 13C NMR determination and Angel Irigoyen Barrio and Dr Ana Romo Hualde, from University of Navarra, for HRMS determination. Dr. Irene de Miguel Turrullols from Small Molecule Discovery Platform, CIMA, University of Navarra is acknowledged for NMR data interpretation. This work was funded by grants from Instituto de Salud Carlos III (ISCIII) PI10/01691, PI13/01469, PI14/01867, PI10/2983, TRASCAN (EPICA), CIBERONC, cofinanciacion FEDER, RTICC RD12/0036/0068, Fundació La Marató de TV3 (20132130-31-32) and ‘Fundación Fuentes Dutor’. B.P. is supported by a Sara Borrell fellowship CD13/00340 and X.A. is a Marie Curie researcher under contract ‘LincMHeM-330598’.S

    The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

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    Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

    Clustering COVID-19 ARDS patients through the first days of ICU admission. An analysis of the CIBERESUCICOVID Cohort

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    Background Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster.Methods Multicenter, observational prospective, and retrospective study of patients admitted due to ARDS related to COVID-19 infection in Spain. Patients were grouped according to a clustering mixed-type data algorithm (k-prototypes) using continuous and categorical readily available variables at baseline and day 3.Results Of 6205 patients, 3743 (60%) were included in the study. According to silhouette analysis, patients were grouped in two clusters. At baseline, 1402 (37%) patients were included in cluster 1 and 2341(63%) in cluster 2. On day 3, 1557(42%) patients were included in cluster 1 and 2086 (57%) in cluster 2. The patients included in cluster 2 were older and more frequently hypertensive and had a higher prevalence of shock, organ dysfunction, inflammatory biomarkers, and worst respiratory indexes at both time points. The 90-day mortality was higher in cluster 2 at both clustering processes (43.8% [n = 1025] versus 27.3% [n = 383] at baseline, and 49% [n = 1023] versus 20.6% [n = 321] on day 3). Four hundred and fifty-eight (33%) patients clustered in the first group were clustered in the second group on day 3. In contrast, 638 (27%) patients clustered in the second group were clustered in the first group on day 3.Conclusions During the first days, patients can be clustered into two groups and the process of clustering patients may change as they continue to evolve. This means that despite a vast majority of patients remaining in the same cluster, a minority reaching 33% of patients analyzed may be re-categorized into different clusters based on their progress. Such changes can significantly impact their prognosis

    Severity of bovine tuberculosis is associated with co-infection with common pathogens in wild boar

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    Co-infections with parasites or viruses drive tuberculosis dynamics in humans, but little is known about their effects in other non-human hosts. This work aims to investigate the relationship between Mycobacterium bovis infection and other pathogens in wild boar (Sus scrofa), a recognized reservoir of bovine tuberculosis (bTB) in Mediterranean ecosystems. For this purpose, it has been assessed whether contacts with common concomitant pathogens are associated with the development of severe bTB lesions in 165 wild boar from mid-western Spain. The presence of bTB lesions affecting only one anatomic location (cervical lymph nodes), or more severe patterns affecting more than one location (mainly cervical lymph nodes and lungs), was assessed in infected animals. In addition, the existence of contacts with other pathogens such as porcine circovirus type 2 (PCV2), Aujeszky's disease virus (ADV), swine influenza virus, porcine reproductive and respiratory syndrome virus, Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae, Haemophilus parasuis and Metastrongylus spp, was evaluated by means of serological, microbiological and parasitological techniques. The existence of contacts with a structured community of pathogens in wild boar infected by M. bovis was statistically investigated by null models. Association between this community of pathogens and bTB severity was examined using a Partial Least Squares regression approach. Results showed that adult wild boar infected by M. bovis had contacted with some specific, non-random pathogen combinations. Contact with PCV2, ADV and infection by Metastrongylus spp, was positively correlated to tuberculosis severity. Therefore, measures against these concomitant pathogens such as vaccination or deworming, might be useful in tuberculosis control programmes in the wild boar. However, given the unexpected consequences of altering any community of organisms, further research should evaluate the impact of such measures under controlled conditions. Furthermore, more research including other important pathogens, such as gastro-intestinal nematodes, will be necessary to complete this picture

    Notes for genera: basal clades of Fungi (including Aphelidiomycota, Basidiobolomycota, Blastocladiomycota, Calcarisporiellomycota, Caulochytriomycota, Chytridiomycota, Entomophthoromycota, Glomeromycota, Kickxellomycota, Monoblepharomycota, Mortierellomycota, Mucoromycota, Neocallimastigomycota, Olpidiomycota, Rozellomycota and Zoopagomycota)

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    Compared to the higher fungi (Dikarya), taxonomic and evolutionary studies on the basal clades of fungi are fewer in number. Thus, the generic boundaries and higher ranks in the basal clades of fungi are poorly known. Recent DNA based taxonomic studies have provided reliable and accurate information. It is therefore necessary to compile all available information since basal clades genera lack updated checklists or outlines. Recently, Tedersoo et al. (MycoKeys 13:1--20, 2016) accepted Aphelidiomycota and Rozellomycota in Fungal clade. Thus, we regard both these phyla as members in Kingdom Fungi. We accept 16 phyla in basal clades viz. Aphelidiomycota, Basidiobolomycota, Blastocladiomycota, Calcarisporiellomycota, Caulochytriomycota, Chytridiomycota, Entomophthoromycota, Glomeromycota, Kickxellomycota, Monoblepharomycota, Mortierellomycota, Mucoromycota, Neocallimastigomycota, Olpidiomycota, Rozellomycota and Zoopagomycota. Thus, 611 genera in 153 families, 43 orders and 18 classes are provided with details of classification, synonyms, life modes, distribution, recent literature and genomic data. Moreover, Catenariaceae Couch is proposed to be conserved, Cladochytriales Mozl.-Standr. is emended and the family Nephridiophagaceae is introduced

    Epizootiologic survey of listeriosis on ruminants from Córdoba province, Spain: serological inquiry

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    A serological inquiry on listeriosis of the domestic ruminants of the province of Cordoba (Spain) was made to know the epizootiology of the disease. The agglutination in tube with 2-mercaptoetanol technique was carried out using somatic antigens of the 1/2 and 4 serological types of Listeria monocytogenes. 2.685 samples of apparently healthy adult ruminants from 286 flocks have been investigated. In sheep we found 10 foci of the infection (11.9 per cent of the investigated flocks). In cattle we detected 15 foci (9.56 per cent). In goats we found 5 foci (10 per cent). In relation to the individuals, in sheep we found 2.10 per cent of infected animals, in cattle 3.35 per cent and in goats 4.07 per cent. The index on infected animals in each of the positive flocks is different according to the studied species, the geographical localization and the serotype. In the whole province we find a mean infection of 29.56 + 12.22 in cattle, 3199 + 13.43 in goats and 17.06 + 9.48 in sheep. The most frequent serotype of L. monocytogenes in the 30 foci investigated was serotype 4 (70 per cent) followed by serotype 1/2 (30 per cent).Los rebaños analizados en la especie ovina; 15 focos (9,86 p.100), en bovinos; y 5 focos (10 p.100), en caprinos. La frecuencia de individuos seropositivos fue de 2,10 p.100 en ovinos; 3,35, en bovinos; y 4,07, en caprinos. En relación a las Se realiza un estudio epizootiológico de listeriosis, mediante encuesta serológica, en rumiantes de la provincia de Córdoba. Utilizamos la técnica de aglutinación en tubo con 2-mercaptoetanol, usando antígeno somáticos de los tipos serológicos 1/2 y 4 de Listeria monocytogenes. La investigación ha sido realizada sobre 2.685 muestras de suero de rumiantes adultos, aparentemente sanos, procedentes de 286 rebaños. Se detectaron 10 focos de infección (11,90 p.100 de los frecuencias de infección dentro de los colectivos seropositivos, se observan valores diferentes según la especie, localización geográfica y tipo serol6gico. Las medias de estas frecuencias se situaron en 31,99 + 13,43 (caprinos), 29,56 + 12,22 (bovinos) y 17,06 + 9,48 (ovinos). De un total de 30 focos diagnosticados, treinta (70 p.100) correspondieron al tipo serológico 4 de L. monocytogenes, frente a nueve focos (30 p.100) del tipo 1/2

    A case of exudative epidermitis in a young wild boar from a Spanish game estate

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    Exudative epidermitis, a porcine disease caused by Staphylococcus hyicus, produces serious economic losses in severely affected herds. In this report, we describe a case of exudative epidermitis in a wild boar presenting specific clinical signs. The affected animal was a female approximately 6 months old, with greasy brown exudates around the mouth and eyes and on the neck and legs, separation of the horn at the bulbs of the heels, necrosis of the tips of the pinnae and tail, and focal ulcerative stomatitis. Multiple septic emboli and necrotic foci were observed in the lung. Staphylococcus hyicus isolates were obtained from affected skin and lungs. This disease and others that occur on wild boar farms, while similar to those described in domestic pigs, tend to produce specific clinical signs in wild boar, such as the pneumonic lesions in this case. Exudative epidermitis in this animal was aggravated by these pneumonic lesions. The increasing economic relevance of wild boar farming has led to an increase in the occurrence of infectious diseases. Knowledge about their epidemiological, clinical, and pathological manifestations in wild boar will facilitate prevention, diagnosis, and treatment, reducing the impact on animal health and economics in this new niche swine production
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