Aortic disease in Marfan syndrome is caused by overactivation of sGC-PRKG signaling by NO

AbstractThoracic aortic aneurysm, as occurs in Marfan syndrome, is generally asymptomatic until dissection or rupture, requiring surgical intervention as the only available treatment. Here, we show that nitric oxide (NO) signaling dysregulates actin cytoskeleton dynamics in Marfan Syndrome smooth muscle cells and that NO-donors induce Marfan-like aortopathy in wild-type mice, indicating that a marked increase in NO suffices to induce aortopathy. Levels of nitrated proteins are higher in plasma from Marfan patients and mice and in aortic tissue from Marfan mice than in control samples, indicating elevated circulating and tissue NO. Soluble guanylate cyclase and cGMP-dependent protein kinase are both activated in Marfan patients and mice and in wild-type mice treated with NO-donors, as shown by increased plasma cGMP and pVASP-S239 staining in aortic tissue. Marfan aortopathy in mice is reverted by pharmacological inhibition of soluble guanylate cyclase and cGMP-dependent protein kinase and lentiviral-mediated Prkg1 silencing. These findings identify potential biomarkers for monitoring Marfan Syndrome in patients and urge evaluation of cGMP-dependent protein kinase and soluble guanylate cyclase as therapeutic targets.</jats:p

III Congreso de innovación docente en clásicas en la Comunidad de Madrid: Los retos de la enseñanza online

Memoria final del PIMCD 58/202

Risk factors and outcome of COVID-19 in patients with hematological malignancies

Background: Prognostic factors of poor outcome in patients with hematological malignancies and COVID-19 are poorly defned. Patients and methods: This was a Spanish transplant group and cell therapy (GETH) multicenter retrospective observational study, which included a large cohort of blood cancer patients with laboratory-confrmed SARS-CoV-2 infection through PCR assays from March 1st 2020 to May 15th 2020. Results: We included 367 pediatric and adult patients with hematological malignancies, including recipients of autologous (ASCT) (n=58) or allogeneic stem cell transplantation (allo-SCT) (n=65) from 41 hospitals in Spain. Median age of patients was 64 years (range 1-93.8). Recipients of ASCT and allo-SCT showed lower mortality rates (17% and 18%, respectively) compared to non-SCT patients (31%) (p=0.02). Prognostic factors identifed for day 45 overall mortality (OM) by logistic regression multivariate analysis included age>70 years [odds ratio (OR) 2.1, 95% con‑ fdence interval (CI) 1.2-3.8, p=0.011]; uncontrolled hematological malignancy (OR 2.9, 95% CI 1.6-5.2, p20 mg/dL (OR 3.3, 95% CI 1.7-6.4, p<0.0001). In multivariate analysis of 216 patients with very severe COVID-19, treatment with azithromycin or low dose corticosteroids was associated with lower OM (OR 0.42, 95% CI 0.2-0.89 and OR 0.31, 95% CI 0.11-0.87, respectively, p=0.02) whereas the use of hidroxycloroquine did not show signifcant improvement in OM (OR 0.64, 95% CI 0.37-1.1, P=0.1). Conclusions: In most patients with hematological malignancies COVID-19 mortality was directly driven by older age, disease status, performance status, as well as by immune (neutropenia) parameters and level of infammation (high CRP). Use of azithromycin and low dose corticosteroids may be of value in very severe COVID-19

Feeding Agro-Industrial By-Products to Light Lambs: Influence on Meat Characteristics, Lipid Oxidation, and Fatty Acid Profile

The aim of this study was to assess the effects of replacing 44% of conventional feeds in a high-cereal concentrate (CON) with by-products (BYP concentrate; 18% corn distillers dried grains with solubles, 18% dried citrus pulp, and 8% exhausted olive cake) on the meat characteristics and fatty acid (FA) profile of fattening light lambs. Two groups of 12 Lacaune lambs were fed concentrate and barley straw ad libitum from 13.8 to 26.0 kg of body weight. There were no differences (p &ge; 0.130) between groups in the pH, chemical composition, color, and texture parameters and in the estimated proportions of pigments in the longissimus dorsi. Feeding the BYP concentrate reduced the concentration of thiobarbituric acid reactive substances (TBARS) in the meat after 6 days of refrigerated storage (unmodified atmosphere), probably due to the greater polyphenol content in this concentrate. Compared with CON-fed lambs, the meat and the subcutaneous fat from BYP-fed lambs had lower saturated and greater polyunsaturated FA content as well as greater n-6/n-3 FA. In summary, feeding a blend of corn distiller dried grains with solubles, dried citrus pulp, and exhausted olive cake did not change the composition of the meat but improved its antioxidant status and FA profile

Feeding Agroindustrial Byproducts to Light Lambs: Influence on Growth Performance, Diet Digestibility, Nitrogen Balance, Ruminal Fermentation, and Plasma Metabolites

The objective of this study was to evaluate the effect of replacing cereals and protein concentrates in a high-cereal concentrate (control) for light lambs with corn distiller’s dried grains with solubles (DDGS; 18%), dried citrus pulp (DCP; 18%), and exhausted olive cake (EOC; 8%) in a byproduct (BYP) concentrate on growth performance, digestibility, ruminal fermentation, and plasma metabolites. Two homogeneous groups of Lacaune lambs (13.8 kg ± 0.25 kg) were fed one of each concentrates and barley straw ad libitum until reaching about 26 kg body weight. There were no differences between groups on feed intake, average daily gain, or feed conversion ratio, but the control diet had greater (p < 0.001) dry matter digestibility. Diet had no effect on post-mortem ruminal pH and total volatile fatty acid concentrations and profile, but NH3-N concentrations were lower (p = 0.003) for the BYP-fed group compared with the control one. However, plasma concentrations of amino acids, total proteins, urea, and hepatic enzymes were not affected by the diet. In conclusion, 44% of feed ingredients in the concentrate for light lambs can be replaced with a mixture of corn DDGS, DCP, and EOC without negatively affecting growing performance and animal health

Effects of Feeding Rumen-Protected Sunflower Seed and Meal Protein on Feed Intake, Diet Digestibility, Ruminal, Cecal Fermentation, and Growth Performance of Lambs

The objective of this study was to analyze the efficacy of a treatment (MAH) of sunflower seed (SS) and meal (SM) with a malic acid solution (1 M; 400 mL/kg) and heating (150 ◦C, 2 h) to protect protein against rumen degradation and to improve the growth of lambs. Two homogeneous groups of 12 Lacaune lambs each (14.2 ± 0.35 kg body weight) were fed either a concentrate including untreated SS and SM or a concentrate with MAH-treated SS and SM. Lambs were fed concentrate and barley straw ad libitum for 40 days (about 26 kg body weight); feed intake and growth of lambs were recorded; blood samples were taken on days 0, 20, and the slaughter day for analysis of urea-N and amino acid-N; diet digestibility was determined; and ruminal and cecal samples were collected after slaughter. The in vitro incubation of both concentrates with sheep ruminal fluid for 12 h showed that the MAH-treatment tended to reduce NH3-N concentrations and increased propionate production. However, there were no differences (p > 0.05) between groups in any of the tested variables in the in vivo trial

Effect of a Diet Supplemented with Malic Acid–Heat (MAH) Treated Sunflower on Carcass Characteristics, Meat Composition and Fatty Acids Profile in Growing Lambs

The objective of the study was to assess the effects of feeding sunflower meal (SM) and seeds (SS) protected against rumen degradation on carcass characteristics and composition and fatty acid (FA) profile of lamb meat. The protection of SM and SS was achieved by treating both feeds with malic acid at 150 ◦C for 2 h (MAH treatment) and in a previous study this treatment was shown to decrease ruminal degradability of protein of both feeds and fat degradability of SS. Two homogeneous groups of 12 lambs each were fed ad libitum high-cereal concentrates and cereal straw from 14 to 26 kg of body weight. The two concentrates differed only in the treatment SM and SS, which were included either untreated (control) or MAH treated. The MAH-fed lambs had greater thickness of dorsal fat (p = 0.016) and greater (p ≤ 0.016) values of the color parameters a* (redness) and C* (chromaticity) of the Rectus abdominis muscle. However, there were no differences in carcass measurements and in water-holding capacity, chemical composition, pH, color, or fatty acid of Longissimus muscle. In summary, the MAH treatment resulted in only subtle changes in meat composition and quality. However, there were no differences between groups in meat chemical composition and fatty acid profile