Adaptaciones metabólicas en vacas lecheras de distintos genotipos holstein bajo dos estrategias de alimentación

El objetivo del trabajo fue profundizar en los mecanismos moleculares relacionados con el metabolismo energético hepático en vacas lecheras Holstein-Friesian de distinto origen genético, sometidas a dos estrategias nutricionales a lo largo de la lactancia. Modelo 1: vacas Holstein-Friesian multíparas sometidas a dos estrategias de alimentación. De los 0 a los 180 días en leche (DEL) las vacas fueron alimentadas con una dieta totalmente mezclada (DTM) ad libitum (G0) o pastorearon Festuca arundinacea o Medicago sativa y fueron suplementadas con concentrado (G1); de los 180 a 250 días todas las vacas pastorearon Festuca arundinacea y fueron suplementadas con una DTM. Modelo 2: vacas Holstein-Friesian de origen genético neozelandés (NZH) o norteamericano (NAH) sometidas a dos estrategias de alimentación, la de máximo pastoreo (MaxP), donde el forraje representó el 67 % del consumo ofrecido (70:30 relación de Medicago sativa y Dactylis glomerata o Festuca arundinacea a forraje conservado) y el 33 % restante se ofreció como concentrado, y la estrategia FixP donde el pastoreo representó el 32 % del consumo ofrecido y el restante se ofreció como DTM. Para el modelo 1 se tomó plasma y biopsias de hígado a los -14, 35, 60, 110, 180 y 250 DEL y para el modelo 2 a los -14, 21, 100 y 180 DEL con el objetivo de caracterizar los perfiles metabólico-endócrinos, la expresión génica de enzimas de las vías metabólicas, la función mitocondrial, los niveles de proteína y las modificaciones postraduccionales. Nuestro trabajo evidenció una disfunción mitocondrial hepática durante la lactancia temprana asociada a los niveles de acetilación de lisinas en proteínas mitocondriales en vacas sometidas a estrategias pastoriles, con una recuperación hacia la lactancia media tardía. Sin embargo, las vacas NAH en la estrategia MaxP no lograron recuperar su función mitocondrial durante la lactancia media tardía y mostraron una más alta expresión de genes asociados a la gluconeogénesis sugiriendo una mayor persistencia que las vacas NZH

Detection of Carbon Monoxide in the Atmosphere of WASP-39b Applying Standard Cross-Correlation Techniques to JWST NIRSpec G395H Data

Carbon monoxide was recently reported in the atmosphere of the hot Jupiter WASP-39b using the NIRSpec PRISM transit observation of this planet, collected as part of the JWST Transiting Exoplanet Community Early Release Science (JTEC ERS) Program. This detection, however, could not be confidently confirmed in the initial analysis of the higher resolution observations with NIRSpec G395H disperser. Here we confirm the detection of CO in the atmosphere of WASP-39b using the NIRSpec G395H data and cross-correlation techniques. We do this by searching for the CO signal in the unbinned transmission spectrum of the planet between 4.6 and 5.0 $\mu$m, where the contribution of CO is expected to be higher than that of other anticipated molecules in the planet's atmosphere. Our search results in a detection of CO with a cross-correlation function (CCF) significance of $6.6 \sigma$ when using a template with only ${\rm ^{12}C^{16}O}$ lines. The CCF significance of the CO signal increases to $7.5 \sigma$ when including in the template lines from additional CO isotopologues, with the largest contribution being from ${\rm ^{13}C^{16}O}$. Our results highlight how cross-correlation techniques can be a powerful tool for unveiling the chemical composition of exoplanetary atmospheres from medium-resolution transmission spectra, including the detection of isotopologues.Comment: Accepted for publication in The Astrophysical Journal Letter

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

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

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

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

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

Heritage and the Sea: Maritime History and Archaeology of the Global Iberian World (15th -18th centuries)

This two-volume set highlights the importance of Iberian shipbuilding in the centuries of the so-called first globalization (15th to 18th), in confluence with an unprecedented extension of ocean navigation and seafaring and a greater demand for natural resources (especially timber), mostly oak (Quercus spp.) and Pine (Pinus spp.). The chapters are framed in a multidisciplinary and interdisciplinary line of research that integrates history, Geographic Information Sciences, underwater archaeology, dendrochronology and wood provenance techniques. This line of research was developed during the ForSEAdiscovery project, which had a great impact in the academic and scientific world and brought together experts from Europe and America. The volumes deliver a state-of-the-art review of the latest lines of research related to Iberian maritime history and archaeology and their developing interdisciplinary interaction with dendroarchaeology. This synthesis combines an analysis of historical sources, the systematic study of wreck-remains and material culture related to Iberian seafaring from the 15th to the 18th centuries, and the application of earth sciences, including dendrochronology. The set can be used as a manual or work guide for experts and students, and will also be an interesting read for non-experts interested in the subject.Volume 1 focuses on the history and archaeology of seafaring and shipbuilding in the Iberian early modern world, complemented by case studies on timber trade and supply for shipbuilding, analysis of shipbuilding treatises, and the application of Geographic Information Systems and Databases (GIS) to the study of shipwrecks.Volume 2 focuses on approaches to the study of shipwrecks including a synthesis of dendro-archaeological results, current interdisciplinary case studies and the specialist study of artillery and anchors.Peer reviewe

Respiratory analysis of coupled mitochondria in cryopreserved liver biopsies

The aim of this work was to develop a cryopreservation method of small liver biopsies for in situ mitochondrial function assessment. Herein we describe a detailed protocol for tissue collection, cryopreservation, high-resolution respirometry using complex I and II substrates, calculation and interpretation of respiratory parameters. Liver biopsies from cow and rat were sequentially frozen in a medium containing dimethylsulfoxide as cryoprotectant and stored for up to 3 months at −80 °C. Oxygen consumption rate studies of fresh and cryopreserved samples revealed that most respiratory parameters remained unchanged. Additionally, outer mitochondrial membrane integrity was assessed adding cytochrome c, proving that our cryopreservation method does not harm mitochondrial structure. In sum, we present a reliable way to cryopreserve small liver biopsies without affecting mitochondrial function. Our protocol will enable the transport and storage of samples, extending and facilitating mitochondrial function analysis of liver biopsies. Keywords: Cryopreservation, Mitochondria, Biopsy, Oxygen consumption rate, High-resolution respirometry, Mitochondrial functio

Hepatic metabolism of grazing cows of two Holstein strains under two feeding strategies with different levels of pasture inclusion.

The objective of the study was to characterize adaptations of hepatic metabolism of dairy cows of two Holstein strains with varying proportions of grazing in the feeding strategy. Multiparous autumn calving Holstein cows of New Zealand (NZH) and North American (NAH) strains were assigned to a randomized complete block design with a 2 x 2 factorial arrangement with two feeding strategies that varied in the proportions of pasture and supplementation: maximum pasture and supplementation with a pelleted concentrate (MaxP) or fixed pasture and supplementation with a total mixed ration (FixP) from May through November of 2018. Hepatic biopsies were taken at - 45 ± 17, 21 ± 7, 100 ± 23 and 180 ± 23 days in milk (DIM), representing prepartum, early lactation, early mid-lactation and late mid-lactation. The effects of DIM, feeding strategy (FS), strain and their interactions were analyzed with mixed models using repeated measures. Cows of both strains had similar triglyceride levels, mitochondrial function and carnitine palmitoyltransferase activity in liver during lactation. However, there was an effect of DIM and FS as liver triglyceride was higher for the MaxP strategy at 21 DIM and both mitochondrial function and carnitine palmitoyltransferase activity in liver were lower for the MaxP strategy at 21 DIM. Hepatic mitochondrial function and acetylation levels were affected by the interaction between strain and feeding strategy as both variables were higher for NAH cows in the MaxP strategy. Mid-lactation hepatic gene expression of enzymes related to fatty acid metabolism and nuclear receptors was higher for NZH than NAH cows. This work confirms the association between liver triglyceride, decreased hepatic mitochondrial function and greater mitochondrial acetylation levels in cows with a higher inclusion of pasture and suggests differential adaptative mechanisms between NAH and NZH cows to strategies with varying proportions of grazing in the feeding strategy