Factores y mecanismos reguladores de la ingesta, apetito y saciedad.

En la alimentación intervienen un conjunto de procesos complejos que permiten al organismo mantener el suministro energético necesario. Todo ello está controlado por mecanismos reguladores de la ingesta y el gasto energético. El comienzo de la ingesta comienza o, bien por deseo o, por necesidad fisiológica y están implicadas diferentes moléculas y rutas. Unas, las orexígenas, generan hambre y otras, las anorexígenas, señalan la finalización de la ingesta. Estas moléculas están reguladas por el hipotálamo y se secretan por la presencia de alimentos en el estómago o por señales del estado metabólico del organismo. Al comer se generan diferentes tipos de señales: estímulos cognitivos, donde entran en juego los sentidos y el placer; las señales preabsortivas, que son aquellas que se generan en el estómago; y las postabsortivas, cuando los nutrientes pasan al torrente sanguíneo, generando señales de saciedad. Además de estas señales, los nutrientes producen saciedad dependiendo de su naturaleza bioquímica, siendo unos más saciantes que otros. El acto de comer no solo comienza por una necesidad fisiológica, sino también participan aquellos factores no fisiológicos que nos producen apetito. La regulación de la ingesta y la saciedad actualmente está siendo muy estudiada debido a que la obesidad, por su estrecha vinculación con las principales causas de morbimortalidad, se ha convertido en un problema de salud pública a nivel mundial. La relación obesidad-resistencia insulínica-diabetes mellitus-hipertensión arterial adquiere cada día mayor importancia, por el papel cada vez más relevante de la obesidad en el desarrollo de cada una de ellas. Por todo ello en este trabajo de fin de grado se han estudiado los mecanismos que regulan este complejo proceso

Relationship between the place of living and mortality in patients with advanced heart failure

Social and environmental factors in advanced heart failure (HF) patients may be crucial to cope with the end stages of the disease. This study analyzes health inequalities and mortality according to place of residence (rural vs urban) in HF patients at advanced stages of the disease. Population-based cohort study including 1148 adult patients with HF attended in 279 primary care centers. Patients were followed for at least 1 year after reaching New York Heart Association IV functional class, between 2010 and 2014. Data came from primary care electronic medical records. Cox regression models were applied to determine the hazard ratios (HR) of mortality. Mean age was 81.6 (SD 8.9) years, and 62% were women. Patients in rural areas were older, particularly women aged > 74 years (p = 0.036), and presented lower comorbidity. Mortality percentages were 59 and 51% among rural and urban patients, respectively (p = 0.030). Urban patients living in the most socio-economically deprived neighborhoods presented the highest rate of health service utilization, particularly with primary care nurses (p-trend < 0.001). Multivariate analyses confirmed that men (HR 1.60, 95% confidence interval (CI) 1.34-1.90), older patients (HR 1.05, 95% CI 1.04-1.06), Charlson comorbidity index (HR 1.16, 95% CI 1.11-1.22), and residing in rural areas (HR 1.35, 95% CI 1.09 to 1.67) was associated with higher mortality risk. Living in rural areas determines an increased risk of mortality in patients at final stages of heart failure

The RNA Polymerase II Factor RPAP1 Is Critical for Mediator-Driven Transcription and Cell Identity

The RNA polymerase II-associated protein 1 (RPAP1) is conserved across metazoa and required for stem cell differentiation in plants; however, very little is known about its mechanism of action or its role in mammalian cells. Here, we report that RPAP1 is essential for the expression of cell identity genes and for cell viability. Depletion of RPAP1 triggers cell de-differentiation, facilitates reprogramming toward pluripotency, and impairs differentiation. Mechanistically, we show that RPAP1 is essential for the interaction between RNA polymerase II (RNA Pol II) and Mediator, as well as for the recruitment of important regulators, such as the Mediator-specific RNA Pol II factor Gdown1 and the C-terminal domain (CTD) phosphatase RPAP2. In agreement, depletion of RPAP1 diminishes the loading of total and Ser5-phosphorylated RNA Pol II on many genes, with super-enhancer-driven genes among the most significantly downregulated. We conclude that Mediator/RPAP1/RNA Pol II is an ancient module, conserved from plants to mammals, critical for establishing and maintaining cell identity.We are grateful to Elisa Varela for assistance with morula and blastocyst fixa- tion. Work in the laboratory of M.S. is funded by the CNIO and the IRB and by grants from the Spanish Ministry of Economy co-funded by the European Regional Development Fund (ERDF) (SAF2013-48256-R), the European Research Co uncil (ERC-2014-AdG/66 9622), the Region al Government of Ma- drid co-funded by the Euro pean Social Fund (ReCaRe project), the Euro pean Union (RISK-IR project), the Botin Foundation and Banco Santander (Santander Universities Glo bal Division), the Ramon Areces Found ation, and the AXA Foundation. S.R. was funded by a contract from the Ramon y Cajal Program(RYC-2011-09242) and by the Spanish Ministry of Economy co- funded by the ERDF (SAF2013-49147- P and SAF2016-80874-PS

Contribution of cardio-vascular risk factors to depressive status in the PREDIMED-PLUS Trial. A cross-sectional and a 2-year longitudinal study

Background Cardio-vascular disease and depression are thought to be closely related, due to shared risk factors. The aim of the study was to determine the association between cardio-vascular risk (CVR) factors and depressive status in a population (55-75 years) with metabolic syndrome (MetS) from the PREDIMED-Plus trial. Methods and findings Participants were classified into three groups of CVR according to the Framingham-based REGICOR function: (1) low (LR), (2) medium (MR) or (3) high/very high (HR). The Beck Depression Inventory-II (BDI-II) was used to assess depressive symptoms at baseline and after 2 years. The association between CVR and depressive status at baseline (n = 6545), and their changes after 2 years (n = 4566) were evaluated through multivariable regression models (logistic and linear models). HR women showed higher odds of depressive status than LR [OR (95% CI) = 1.78 (1.26, 2.50)]. MR and HR participants with total cholesterol <160 mg/mL showed higher odds of depression than LR [OR (95% CI) = 1.77 (1.13, 2.77) and 2.83 (1.25, 6.42) respectively)] but those with total cholesterol ¿280 mg/mL showed lower odds of depression than LR [OR (95% CI) = 0.26 (0.07, 0.98) and 0.23 (0.05, 0.95), respectively]. All participants decreased their BDI-II score after 2 years, being the decrease smaller in MR and HR diabetic compared to LR [adjusted mean±SE = -0.52±0.20, -0.41 ±0.27 and -1.25±0.31 respectively). MR and HR participants with total cholesterol between 240-279 mg/mL showed greater decreases in the BDI-II score compared to LR (adjusted mean±SE = -0.83±0.37, -0.77±0.64 and 0.97±0.52 respectively). Conclusions Improving cardiovascular health could prevent the onset of depression in the elderly. Diabetes and total cholesterol in individuals at high CVR, may play a specific role in the precise response.The PREDIMED-Plus trial was supported by the European Research Council through a grant to MAM (Advanced Research Grant 2013-2018; 340918). The project was also supported by the official funding agency for biomedical research of the Spanish Government (ISCIII) through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund (four coordinated FIS projects), who awarded grants to JS and JV (PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732 and PI17/00926). The International Nut&Dried Fruit Council-FESNAD also provided funding through a grant to MAM (201302), and Recercaixa also awarded a grant to JS (2013ACUP00194). The Department of Health, Generalitat de Cataluña by the calls 'Acció instrumental de programes de recerca orientats en lámbit de la recercaila innovació en salut' and 'Pla estrategic de recerca i innovació en salut (PERIS),' also awarded a grant to FF (SLT006/17/00246). This research was also partially funded by: Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, PI0137/2018); Generalitat Valenciana (PROMETEO/2017/017); SEMERGEN, CIBEROBN, FEDER and ISCIII (CB06/03); EU-H2020 Grants (Eat2beNICE/h2020-sfs-2016-2, ref.728018; PRIME/h2020-SC1-BHC-2018-2020, ref: 847879)

IL-6 serum levels predict severity and response to tocilizumab in COVID-19: An observational study

Background: Patients with coronavirus disaese 2019 (COVID-19) can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome requiring invasive mechanical ventilation (IMV). Because IL-6 is a relevant cytokine in acute respiratory distress syndrome, the blockade of its receptor with tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19. Objective: We sought to determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ. Methods: A retrospective observational study was performed in hospitalized patients diagnosed with COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with preadministration and postadministration of TCZ. Multivariable logistic and linear regressions and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio, or mortality. Results: One hundred forty-six patients were studied, predominantly males (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels greater than 30 pg/mL was the best predictor for IMV (odds ratio, 7.1; P < .001). Early administration of TCZ was associated with improvement in oxygenation (arterial oxygen tension/fraction of inspired oxygen ratio) in patients with high IL-6 (P = .048). Patients with high IL-6 not treated with TCZ showed high mortality (hazard ratio, 4.6; P = .003), as well as those with low IL-6 treated with TCZ (hazard ratio, 3.6; P = .016). No relevant serious adverse events were observed in TCZ-treated patients. Conclusions: Baseline IL-6 greater than 30 pg/mL predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administrationThis study was funded by Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and Instituto de Salud Carlos III (grant nos. RD16/0011/0012 and PI18/ 0371 to I.G.A., grant no. PI19/00549 to A.A., and grant no. SAF2017-82886-R to F.S.-M.) and co-funded by the European Regional Development Fund. The study was also funded by ‘‘La Caixa Banking Foundation’’ (grant no. HR17-00016 to F.S.-M.) and ‘‘Fondos Supera COVID19’’ by Banco de Santander and CRUE. None of these sponsors have had any role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publicatio

Gorilla Park: A Sustainable Space for All (Mobility pilot project)

This project explores urban design and urban systems solutions to address issues of shared mobility, accessibility and urban fragmentation. It is a pilot project to create a park and a shared mobility hub in the borough of Rosemont-La-Petite-Patrie in Montreal. This is to be a node of many in a metropolitan-wide shared mobility system. A shared mobility approach to city planning incorporates notions of Transportation Oriented Development (TOD) and Pedestrian Oriented Development (POD) and links it to notions of smart cities and autonomous transportation. The challenge at hand was to create a public space that incorporates these questions as well as notions of placemaking, community planning and open urbanisms. The project is part of an urban design studio taught in the Department of Geography Planning and Environment at Concordia University in Montreal, and it takes place in the context of the first edition of the CitéStudio Montreal program, which fosters collaborations between academics, students and the city government. The solutions explored in this project were conceived by the students of URBS333 - Urban Laboratory (class of 2019-2020) under the supervision of the instructor (S. De la Llata) and in collaboration with stakeholders and neighbours of Gorilla Park. The solutions are divided into five thematic axes (Sustainability, Mobility and Accessibility, Community Engagement, Hard Design and Soft Design)

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

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

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements