Empagliflozin reduces vascular damage and cognitive impairment in a mixed murine model of Alzheimer's disease and type 2 diabetes

Background Both Alzheimer's disease (AD) and type 2 diabetes (T2D) share common pathological features including inflammation, insulin signaling alterations, or vascular damage. AD has no successful treatment, and the close relationship between both diseases supports the study of antidiabetic drugs to limit or slow down brain pathology in AD. Empagliflozin (EMP) is a sodium-glucose co-transporter 2 inhibitor, the newest class of antidiabetic agents. EMP controls hyperglycemia and reduces cardiovascular comorbidities and deaths associated to T2D. Therefore, we have analyzed the role of EMP at the central level in a complex mouse model of AD-T2D. Methods We have treated AD-T2D mice (APP/PS1xdb/db mice) with EMP 10 mg/kg for 22 weeks. Glucose, insulin, and body weight were monthly assessed. We analyzed learning and memory in the Morris water maze and the new object discrimination test. Postmortem brain assessment was conducted to measure brain atrophy, senile plaques, and amyloid-beta levels. Tau phosphorylation, hemorrhage burden, and microglia were also measured in the brain after EMP treatment. Results EMP treatment helped to maintain insulin levels in diabetic mice. At the central level, EMP limited cortical thinning and reduced neuronal loss in treated mice. Hemorrhage and microglia burdens were also reduced in EMP-treated mice. Senile plaque burden was lower, and these effects were accompanied by an amelioration of cognitive deficits in APP/PS1xdb/db mice. Conclusions Altogether, our data support a feasible role for EMP to reduce brain complications associated to AD and T2D, including classical pathological features and vascular disease, and supporting further assessment of EMP at the central level

Characterization of polypropylene–polyethylene blends by temperature rising elution and crystallization analysis fractionation

The introduction of single-site catalysts in the polyolefins industry opens new routes to design resins with improved performance through multicatalyst-multireactor processes. Physical combination of various polyolefin types in a secondary extrusion process is also a common practice to achieve new products with improved properties. The new resins have complex structures, especially in terms of composition distribution, and their characterization is not always an easy task. Techniques like temperature rising elution fractionation (TREF) or crystallization analysis fractionation (CRYSTAF) are currently used to characterize the composition distribution of these resins. It has been shown that certain combinations of polyolefins may result in equivocal results if only TREF or CRYSTAF is used separately for their characterization

Isquemia mesentérica: manejo endovascular

Mesenteric ischaemia is a condition that may be very severe and potentially lethal particularly in the acute presentation. Early treatment is crucial. We present four consecutive cases managed by our team with thrombosis or dissection or aneurysm of the superior mesenteric artery and the celiac trunk reviewing indications and treatment implemented. Multiple successful endovascular procedures were used in all cases avoiding progression to lethal consequences. None of the patients required an open surgical procedure. Therefore, endovascular procedures are feasible in these patients avoiding intestinal necrosis as well as the need for open surgeries.La isquemia mesentérica es una condición que puede volverse muy grave y ser letal, más aún en los casos agudos. Un tratamiento precoz es muy importante. Se presentaron cuatro casos consecutivos tratados por nuestro equipo con trombosis, o disección o aneurismas de arterias mesentérica superior y tronco celíaco, se revisaron las indicaciones y se evaluaron los tratamientos llevados a cabo. Se utilizaron procedimientos endovasculares en todos, técnicamente en forma exitosa, evitando que progrese a un desenlace peligroso. Hubo diversidad de técnicas endovasculares adaptándolas a cada caso. En ningún paciente se requirió un acceso quirúrgico abierto para completar el tratamiento realizando las intervenciones prontas. El manejo endovascular de las lesiones mesentéricas es factible y replicable, y en nuestros casos podría haber prevenido una necrosis intestinal así como la necesidad de cirugías resectivas

Liraglutide Reduces Vascular Damage, Neuronal Loss, and Cognitive Impairment in a Mixed Murine Model of Alzheimer's Disease and Type 2 Diabetes

Alzheimer's disease is the most common form of dementia, and epidemiological studies support that type 2 diabetes (T2D) is a major contributor. The relationship between both diseases and the fact that Alzheimer's disease (AD) does not have a successful treatment support the study on antidiabetic drugs limiting or slowing down brain complications in AD. Among these, liraglutide (LRGT), a glucagon-like peptide-1 agonist, is currently being tested in patients with AD in the Evaluating Liraglutide in Alzheimer's Disease (ELAD) clinical trial. However, the effects of LRGT on brain pathology when AD and T2D coexist have not been assessed. We have administered LRGT (500 mu g/kg/day) to a mixed murine model of AD and T2D (APP/PS1xdb/db mice) for 20 weeks. We have evaluated metabolic parameters as well as the effects of LRGT on learning and memory. Postmortem analysis included assessment of brain amyloid-beta and tau pathologies, microglia activation, spontaneous bleeding and neuronal loss, as well as insulin and insulin-like growth factor 1 receptors. LRGT treatment reduced glucose levels in diabetic mice (db/db and APP/PS1xdb/db) after 4 weeks of treatment. LRGT also helped to maintain insulin levels after 8 weeks of treatment. While we did not detect any effects on cortical insulin or insulin-like growth factor 1 receptor m-RNA levels, LRGT significantly reduced brain atrophy in the db/db and APP/PS1xdb/db mice. LRGT treatment also rescued neuron density in the APP/PS1xdb/db mice in the proximity (p = 0.008) far from amyloid plaques (p < 0.001). LRGT reduced amyloid plaque burden in the APP/PS1 animals (p < 0.001), as well as A beta aggregates levels (p = 0.046), and tau hyperphosphorylation (p = 0.009) in the APP/PS1xdb/db mice. Spontaneous bleeding was also ameliorated in the APP/PS1xdb/db animals (p = 0.012), and microglia burden was reduced in the proximity of amyloid plaques in the APP/PS1 and APP/PS1xdb/db mice (p < 0.001), while microglia was reduced in areas far from amyloid plaques in the db/db and APP/PS1xdb/db mice (p < 0.001). This overall improvement helped to rescue cognitive impairment in AD-T2D mice in the new object discrimination test (p < 0.001) and Morris water maze (p < 0.001). Altogether, our data support the role of LRGT in reduction of associated brain complications when T2D and AD occur simultaneously, as regularly observed in the clinical arena.CH-B: predoctoral fellowship. University of Cadiz. PA-M: predoctoral fellowship. Instituto de Investigacion Biomedica de la Provincia de Cadiz (INIBICA). MG-A: Agencia Estatal de Investigacion. Ministerio de Ciencia e Innovacion. Programa Estatal de Generacion de Conocimiento y Fortalecimiento Cientifico y Tecnologico del Sistema de I C D C i y del Programa Estatal de I + D + i Orientada a los Retos de la Sociedad, del Plan Estatal de Investigacion Cientifica y Tecnica y de Innovacion 2017-2020 (PID2020115499RB-I0). Programa Estatal de I C D C I orientada a los Retos de la Sociedad (BFU 2016-75038-R), financed by the Agencia Estatal de Investigacion (AEI) and the Fondo Europeo de Desarrollo Regional (FEDER), Ministerio de Ciencia, Innovacion y Universidades. Subvencion para la financiacion de la Investigacion y la Innovacion Biomedica y en Ciencias de la Salud en el Marco de la Iniciativa Territorial Integrada 2014-2020 para la Provincia de Cadiz. Consejeria de Salud. Junta de Andalucia. Union Europea, financed by the Fondo de Desarrollo Regional (FEDER) (PI-0008-2017)

Precariedad, exclusión social y modelo de sociedad: lógicas y efectos subjetivos del sufrimiento social contemporáneo (IV). Innovación docente en Filosofía

El PIMCD “Precariedad, exclusión social y modelo de sociedad: lógicas y efectos subjetivos del sufrimiento social contemporáneo (IV). Innovación docente en Filosofía” constituye la cuarta edición de un PIMCD que ha recibido financiación en las últimas convocatorias de PIMCD UCM, de los que se han derivado actividades de formación para estudiantes de Grado, Máster y Doctorado y al menos 3 publicaciones colectivas publicadas por Ediciones Complutense, Siglo XXI y Palgrave McMillan

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

Supercritical carbon dioxide extraction of oil and minor lipid compounds of cake byproduct from Brazil nut (Bertholletia excelsa) beverage production

Supercritical carbon dioxide extraction (SC-CO2) was performed to recover the lipid fraction of the cake by-product from Brazil nut beverage (BNM) production. Extraction kinetics and the effect of pressure and temperature on the yield, oil recovery, fatty acid (FA) profile and minor lipid compounds were evaluated. The modeling of the kinetic assays indicated that most of the oil is readily accessible and the extraction velocity is dominated by the oil solubility. High yield with c.a. 100% oil recovery was achieved at 400 bar and 60 °C. While the FA profile of extracts did not present relevant variations with the extraction conditions, higher content of squalene and β-sitosterol (590.8 and 283.9 mg/g extract) were obtained at the lowest pressure and highest temperature assessed (200 bar and 60 °C). Therefore, SC-CO2 extraction is a suitable technique to recover the oil and other minor lipid bioactive compounds of the cake by-product from BNM production, with a potential application in foods, cosmetics or nutraceuticals.The authors gratefully acknowledge the financial support from Comunidad Autónoma de Madrid (ALIBIRD, project: P2013/ABI2728) and RTA2015-00044-C02-02 project from the Spanish Ministry of Science and Innovation. Thanks to the Universidad Nacional Amazónica de Madre de Dios (UNAMAD, Perú) for the documentary support for the importation of the samples. Wilson V. Vasquez thanks to the “Beca presidente de la República” for his predoctoral scholarship of the postgraduate program from the Ministry of Education of the Republic of Peru.Peer reviewe

Supercritical carbon dioxide extraction of oil and minor lipid compounds of cake byproduct from Brazil nut (Bertholletia excelsa) beverage production

Supercritical carbon dioxide extraction (SC-CO2) was performed to recover the lipid fraction of the cake by-product from Brazil nut beverage (BNM) production. Extraction kinetics and the effect of pressure and temperature on the yield, oil recovery, fatty acid (FA) profile and minor lipid compounds were evaluated. The modeling of the kinetic assays indicated that most of the oil is readily accessible and the extraction velocity is dominated by the oil solubility. High yield with c.a. 100% oil recovery was achieved at 400 bar and 60 °C. While the FA profile of extracts did not present relevant variations with the extraction conditions, higher content of squalene and β-sitosterol (590.8 and 283.9 mg/g extract) were obtained at the lowest pressure and highest temperature assessed (200 bar and 60 °C). Therefore, SC-CO2 extraction is a suitable technique to recover the oil and other minor lipid bioactive compounds of the cake by-product from BNM production, with a potential application in foods, cosmetics or nutraceuticalsThe authors gratefully acknowledge the financial support from Comunidad Autónoma de Madrid (ALIBIRD, project: P2013/ABI2728) and RTA2015-00044-C02-02 project from the Spanish Ministry of Science and Innovatio