Feeding ecology and community streucture of mesopelagic fishes in the Western Mediterranean = Ecología trófica y estructura de la comunidad de peces mesopelágicos del Mediterráneo Occidental

En esta tesis doctoral se ha estudiado la relación de las poblaciones de peces mesopelágicos (Myctophiformes y Stomiiformes) con el medio pelágico, analizando el posible efecto de factores físicos y biológicos en su ecología trófica, y caracterizando su papel ecológico en un sistema oligotrófico. Los mictófidos son elementos claves de las cadenas tróficas al efectuar extensas migraciones diarias verticales, actuando como vectores de flujo de materia orgánica. El presente estudio se desarrolló en las proximidades de Mallorca en otoño (período de mezcla) y verano (estratificación). Se ha investigado el comportamiento trófico y la distribución vertical de peces mesopelágicos, describiendo los cambios ontogénicos en la dieta. Estos aspectos han sido apenas estudiados en juveniles y adultos en el Mediterráneo occidental. El estudio abarca las especies más abundantes y frecuentes de mictófidos y stomiiformes. Las especies objeto de estudio responden a dos morfotipos y dinámicas diferentes: i) el stomiiforme Cyclothone braueri tiene una morfología estilizada y grácil que podría relacionarse con su comportamiento letárgico; ii) las especies de mictófidos realizan migraciones diarias, lo que requiere una musculatura y desarrollo osteol ógico más robustos. Siguiendo el patrón general observado en los océanos, los mictófidos del mediterráneo permanecen en aguas profundas durante el día, y comienzan a ascender al atardecer y a lo largo de la noche, concentrándose en las capas superficiales para alimentarse. El cálculo de la incidencia alimentaria diurna y nocturna determinó que los adultos de mictófidos tienen hábitos principalmente nocturnos, coincidiendo con el momento en que el plancton está más concentrado en la superficie. En cambio, los stomiiformes C. braueri y Argyropelecus hemigymus mostraron hábitos de alimentación intermitente tanto de día como de noche. También se observó alta incidencia alimentaria en los individuos adultos y no migradores de Lampanyctus crocodilus, los cuales capturan sus presas cerca del fondo. La utilización de sondas acústicas para la detección de organismos mesopelágicos por primera vez en el Mar Mediterráneo, permitió observar la formación de densas agregaciones de mictófidos en la superficie y próximos a 400 m de profundidad (capa de reflexión profunda), aunque no toda la población respondió a esta dinámica migratoria. Los estadios de mayor edad de los myctófidos Notoscopelus elongatus y L. crocodilus constituyeron una excepción a este patrón, permaneciendo asociados a las capas profundas. Existe una elevada heterogeneidad en la composición dietética intraspecífica junto a un amplio solapamiento interespecífico. La mayor parte de las especies exhibieron estrategias de alimentaci ón mixtas con un patrón generalista,pero revelando cierto grado de selectividad en función de la morfología y tamaño de la presa. El estudio de la dieta se completó a lo largo del ciclo vital de Lampanyctus pusillus, una especie frecuente en la cuenca mediterránea pero hábitos desconocidos. Los resultados revelaron que se trata de uno de los mictófidos más voraces durante el estadio larvario. Se observó una tendencia ontogénica hacia la selección de presas de mayor valor energético o cuya captura supone una menor inversión de energía. Este estudio ha mostrado como los peces mesopel ágicos se alimentan de un amplio espectro de taxones del meso y macrozooplancton. Los copépodos calanoides constituyeron su base dietética en términos de abundancia numérica. Sin embargo, los eufausiáceos y pequeños peces fueron importantes en términos de biomasa. Desde el punto de vista ontogénico, mictófidos y stomiiformes adultos aumentaron el contenido medio en carbono, y el tamaño de las presas, respecto a los juveniles, a pesar de que no se observaron tendencias en la amplitud de sus nichos tróficos con la edadMesopelagic fish populations from the orders Myctophiformes and Stomiiformes were investigated to determine the potential effects of physical and biological factors on their trophic ecology, and characterize the ecological role that have in an oligotrophic system such as the western Mediterranean. Myctophids are key components of the trophic webs since they perform extensive diel migrations throughout the water column, acting as vectors of matter fluxes. This study was developed in a region off the Balearic Islands during the late autumn (water mixing period) and summer (stratification of the water column). Trophic behaviour, vertical distribution, and ontogenetic dietary shifts of mesopelagic fishes were analysed. These aspects have been hardly reported in juveniles and adults from this region. The present study comprises the most abundant and frequent species of myctophids and stomiiforms. The target species were assigned to contrasting morphotypes and behaviours: i.e., the stomiiform Cyclothone braueri has a slender body shape, which could be related to a lethargic behaviour, whilst migratory myctophids are characterised by a robust musculature and osteological development. Accordingly with the general pattern observed in the oceans, Mediterranean myctophids stay at deep waters during the day and start their diel ascension at dusk, aggregating in the near-surface for foraging. The calculation of day and night feeding incidences revealed that most adult myctophids were nocturnal feeders, coinciding with the day period in which zooplankton concentrates in the surface. The stomiiforms C. braueri and Argyropelecus hemigymus showed intermittent feeding at both day and night-time. High feeding incidence at daytime was also observed for the oldest and non-migratory individuals of Lampanyctus crocodilus that captured prey organisms close to the bottom, acquiring benthopelagic habits. The implementation of acoustic techniques to detect mesopelagic organisms by first time in the Mediterranean Sea, allowed observation of dense aggregations of myctophids and other organisms near the surface and at ca. 400 m depth (Deep Scattering Layer). However, not all the specimens of the myctophid populations responded to this migratory behavior. The oldest stages of Notoscopelus elongatus and L. crocodilus were an exception to this pattern. The dietary patterns and ontogenetic shifts throughout the whole life of the myctophid Lampanyctus pusillus were reported, as it is a frequent but barely studied species in the western Mediterranean. Larvae were very voracious in comparison with other similar pelagic larvae from the Mediterranean. For this species, it was observed an ontogenetic shift towards the selection of larger or more nutritive prey or certain organisms that could be easily captured as a result of an improvement of the swimming skills and catchability. However, trophic niche breadth did not showed a significant trend with growth. This study showed that mesopelagic fishes feed on a wide range of meso and macrozooplankton taxa. Calanoid copepods were the major diet components terms of number. However, euphausiids and small fishes were important prey in terms of biomass and carbon content. High interspecific diet overlapping was detected, concurrently with notable heterogeneity in diet composition at intraspecific level. Most species exhibited mixed feeding strategies with rather generalist patterns, but some degree of prey selectivity depending on the prey size and morphology. The data on the feeding patterns and diet composition of the fish species studied in this thesis were highly valuable, since they could be required for modeling some aspects of the biological communities in the western Mediterranean. Moreover, the results of fish diets and vertical distributions are of importance in the study of the downward transport of organic matter throughout the water column that is widely unknown at global scale

Clinical outcomes after CPX-351 in patients with high-risk acute myeloid leukemia: A comparison with a matched cohort from the Spanish PETHEMA registry

Acute myeloid leukemia; Clinical observations; Intensive chemotherapyLeucemia mieloide aguda; Observaciones clínicas; Quimioterapia intensivaLeucèmia mieloide aguda; Observacions clíniques; Quimioteràpia intensivaBackground CPX-351 is approved for the treatment of therapy related acute myeloid leukemia (t-AML) and AML with myelodysplastic related changes (MRC-AML). The benefits of this treatment over standard chemotherapy has not been addressed in well matched cohorts of real-life patients. Methods Retrospective analysis of AML patients treated with CPX-351 as per routine practice. A propensity score matching (PSM) was used to compare their main outcomes with those observed in a matched cohort among 765 historical patients receiving intensive chemotherapy (IC), all of them reported to the PETHEMA epidemiologic registry. Results Median age of 79 patients treated with CPX-351 was 67 years old (interquartile range 62–71), 53 were MRC-AML. The complete remission (CR) rate or CR without recovery (CRi) after 1 or 2 cycles of CPX-351 was 52%, 60-days mortality 18%, measurable residual disease <0.1% in 54% (12 out of 22) of them. Stem cell transplant (SCT) was performed in 27 patients (34%), median OS was 10.3 months, and 3-year relapse incidence was 50%. Using PSM, we obtained two comparable cohorts treated with CPX-351 (n = 52) or IC (n = 99), without significant differences in CR/CRi (60% vs. 54%) and median OS (10.3 months vs. 9.1 months), although more patients were bridged to SCT in the CPX-351 group (35% vs. 12%). The results were confirmed when only 3 + 7 patients were included in the historical cohort. In multivariable analyses, SCT was associated with better OS (HR 0.33 95% CI: 0.18–0.59), p < 0.001. Conclusion Larger post-authorization studies may provide evidence of the clinical benefits of CPX-351 for AML in the real-life setting.This study was funded in part by a research grant from the Jazz Pharmaceuticals

MesopTroph, a database of trophic parameters to study interactions in mesopelagic food webs

Mesopelagic organisms play a crucial role in marine food webs, channelling energy across the predator-prey network and connecting depth strata through their diel vertical migrations. The information available to assess mesopelagic feeding interactions and energy transfer has increased substantially in recent years, owing to the growing interest and research activity in the mesopelagic realm. However, such data have not been systematically collated and are difficult to access, hampering estimation of the contribution of mesopelagic organisms to marine ecosystems. Here we present MesopTroph, a georeferenced database of diet, trophic markers, and energy content of mesopelagic and other marine taxa compiled from 203 published and non-published sources. MesopTroph currently includes data on stomach contents, carbon and nitrogen stable isotopes, major and trace elements, energy density, fatty acids, trophic positions, and diet proportion estimates for 498 species/genera. MesopTroph will be expanded with new data emerging from ongoing studies. MesopTroph provides a unique tool to investigate trophic interactions and energy flow mediated by mesopelagic organisms, and to evaluate the ecosystem services of this community

Nrf2 Activation Provides Atheroprotection in Diabetic Mice Through Concerted Upregulation of Antioxidant, Anti-inflammatory, and Autophagy Mechanisms

Interactive relationships between metabolism, inflammation, oxidative stress, and autophagy in the vascular system play a key role in the pathogenesis of diabetic cardiovascular disease. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a stress-sensitive guarantor of cellular homeostasis, which cytoprotective contributions extend beyond the antioxidant defense. We investigated the beneficial effects and underlying mechanisms of the Nrf2 inducer tert-butyl hydroquinone (tBHQ) on diabetes-driven atherosclerosis. In the experimental model of streptozotocin-induced diabetes in apolipoprotein E-deficient mice, treatment with tBHQ increased Nrf2 activity in macrophages and vascular smooth muscle cells within atherosclerotic lesions. Moreover, tBHQ significantly decreased the size, extension and lipid content of atheroma plaques, and attenuated inflammation by reducing lesional macrophages (total number and M1/M2 phenotype balance), foam cell size and chemokine expression. Atheroprotection was accompanied by both systemic and local antioxidant effects, characterized by lower levels of superoxide anion and oxidative DNA marker 8-hydroxy-2′-deoxyguanosine, reduced expression of NADPH oxidase subunits, and increased antioxidant capacity. Interestingly, tBHQ treatment upregulated the gene and protein expression of autophagy-related molecules and also enhanced autophagic flux in diabetic mouse aorta. In vitro, Nrf2 activation by tBHQ suppressed cytokine-induced expression of pro-inflammatory and oxidative stress genes, altered macrophage phenotypes, and promoted autophagic activity. Our results reinforce pharmacological Nrf2 activation as a promising atheroprotective approach in diabetes, according to the plethora of cytoprotective mechanisms involved in the resolution of inflammation and oxidative stress, and restoring autophagy

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Critical role of types 2 and 3 deiodinases in the negative regulation of gene expression by T 3 in the mouse cerebral cortex

Thyroid hormones regulate brain development and function through the control of gene expression, mediated by binding of T 3 to nuclear receptors. Brain T 3 concentration is tightly controlled by homeostatic mechanisms regulating transport and metabolism of T 4 and T 3. We have examined the role of the inactivating enzyme type 3 deiodinase (D3) in the regulation of 43 thyroid hormone-dependent genes in the cerebral cortex of 30-d-old mice. D3 inactivation increased slightly the expression of two of 22 positively regulated genes and significantly decreased the expression of seven of 21 negatively regulated genes. Administration of high doses of T 3 led to significant changes in the expression of 12 positive genes and three negative genes in wild-type mice. The response to T 3 treatment was enhanced in D3-deficient mice, both in the number of genes and in the amplitude of the response, demonstrating the role of D3 in modulating T 3 action. Comparison of the effects on gene expression observed in D3 deficiency with those in hypothyroidism, hyperthyroidism, and type 2 deiodinase (D2) deficiency revealed that the negative genes are more sensitive to D2 and D3 deficiencies than the positive genes. This observation indicates that, in normal physiological conditions, D2 and D3 play critical roles in maintaining local T 3 concentrations within a very narrow range. It also suggests that negatively and positively regulated genes do not have the same physiological significance or that their regulation by thyroid hormone obeys different paradigms at the molecular or cellular levels. Copyright © 2012 by The Endocrine Society.This work was supported by Grants SAF2008-01168 and SAF2008-00429-E from the Ministry of Education and Science of Spain, Grant LSHM-CT-2005-018652 from the European Union Integrated ProjectCRESCENDO,a grant from the Center for Biomedical Research on Rare Diseases, an initiative of the Instituto de Salud Carlos III, and by Grant NIMH-083220 from the National Institute of Mental Health. A.C. was recipient of a predoctoral fellowship from the Plan Nacional de I+D+i.Peer Reviewe

Restoration of ecosystem functionality: the value of species interactions

La restauración de los ecosistemas naturales se ha centrado tradicionalmente en recuperar la riqueza específica, en un intento por recobrar la funcionalidad ecosistémica. Sin embargo, las especies que conforman la comunidad de un ecosistema natural no viven de manera aislada, sino que interactúan con otras, formando redes ecológicas complejas. Sabemos que las actividades humanas (p. ej., la tala selectiva o la expansión de la agricultura) modifican la estructura de dichas redes de interacción, con importantes efectos sobre la funcionalidad de los ecosistemas naturales. A pesar de esto, aún no sabemos si las técnicas de restauración que usamos hoy en día son capaces de restablecer la estructura de estas redes y, por lo tanto, la funcionalidad relacionada. En este artículo, exponemos las razones por las cuales creemos que la restauración ha de tener en cuenta la estructura de las redes de interacciones entre especies. Revisamos cómo afectan a esta estructura los diferentes tipos de perturbaciones y proponemos posibles vías para el estudio y la aplicación de estas ideas. Esperamos que esta perspectiva contribuya a mejorar el manejo y la gestión del medio natural ante la necesidad de acometer acciones de restauración en respuesta al cambio globalRestoration of natural ecosystems has traditionally focused on recovering specific richness to recover ecosystem functionality. However, species within a natural ecosystem are not isolated, they interact with others forming complex ecological networks. We know that human activities (such as selective logging or agriculture expansion) modify the structure of these interaction networks, with important effects on the functionality of ecosystems. Despite this, we still do not know whether techniques implemented today are able to restore the structure of these networks and their related functionality. In this article, we expose the reasons why we believe that restoration should consider the structure of the networks of species interactions. We review how the different types of disturbances affect this structure and we propose possible avenues for the study and application of these ideas. We hope that this perspective will help improve the management of the natural environment in response to global changeS